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Sample records for single retinal ganglion

  1. Imaging of single retinal ganglion cell with differential interference contrast microscopy (Conference Presentation)

    Science.gov (United States)

    Oh, Juyeong; Kim, Yu Jeong; Kim, Chul-Ki; Lee, Taik Jin; Seo, Mina; Lee, Seok; Woo, Deok Ha; Jun, Seong Chan; Park, Ki-Ho; Kim, Seok Hwan; Kim, Jae Hun

    2017-02-01

    Glaucoma is a progressive optic neuropathy, characterized by the selective loss of retinal ganglion cells (RGCs). Therefore, monitoring the change of number or morphology of RGC is essential for the early detection as well as investigation of pathophysiology of glaucoma. Since RGC layer is transparent and hyporeflective, the direct optical visualization of RGCs has not been successful so far. Therefore, glaucoma evaluation mostly depends on indirect diagnostic methods such as the evaluation of optic disc morphology or retinal nerve fiber layer thickness measurement by optical coherence tomography. We have previously demonstrated single photoreceptor cell imaging with differential interference contrast (DIC) microscopy. Herein, we successfully visualized single RGC using DIC microscopy. Since RGC layer is much less reflective than photoreceptor layer, various techniques including the control of light wavelength and bandwidth using a tunable band pass filter were adopted to reduce the chromatic aberration in z-axis for higher and clearer resolution. To verify that the imaged cells were the RGCs, the flat-mounted retina of Sprague-Dawley rat, in which the RGCs were retrogradely labeled with fluorescence, was observed by both fluorescence and DIC microscopies for direct comparison. We have confirmed that the cell images obtained by fluorescence microscopy were perfectly matched with cell images by DIC microscopy. As conclusion, we have visualized single RGC with DIC microscopy, and confirmed with fluorescence microscopy.

  2. Changes in ganglion cells during retinal degeneration.

    Science.gov (United States)

    Saha, Susmita; Greferath, Ursula; Vessey, Kirstan A; Grayden, David B; Burkitt, Anthony N; Fletcher, Erica L

    2016-08-04

    Inherited retinal degeneration such as retinitis pigmentosa (RP) is associated with photoreceptor loss and concomitant morphological and functional changes in the inner retina. It is not known whether these changes are associated with changes in the density and distribution of synaptic inputs to retinal ganglion cells (RGCs). We quantified changes in ganglion cell density in rd1 and age-matched C57BL/6J-(wildtype, WT) mice using the immunocytochemical marker, RBPMS. Our data revealed that following complete loss of photoreceptors, (∼3months of age), there was a reduction in ganglion cell density in the peripheral retina. We next examined changes in synaptic inputs to A type ganglion cells by performing double labeling experiments in mice with the ganglion cell reporter lines, rd1-Thy1 and age-matched wildtype-Thy1. Ribbon synapses were identified by co-labelling with CtBP2 (RIBEYE) and conventional synapses with the clustering molecule, gephyrin. ON RGCs showed a significant reduction in RIBEYE-immunoreactive synapse density while OFF RGCs showed a significant reduction in the gephyrin-immmunoreactive synapse density. Distribution patterns of both synaptic markers across the dendritic trees of RGCs were unchanged. The change in synaptic inputs to RGCs was associated with a reduction in the number of immunolabeled rod bipolar and ON cone bipolar cells. These results suggest that functional changes reported in ganglion cells during retinal degeneration could be attributed to loss of synaptic inputs. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Retinal ganglion cell topography in elasmobranchs.

    Science.gov (United States)

    Bozzano, A; Collin, S P

    2000-04-01

    Retinal wholemounts are used to examine the topographic distribution of retinal cells within the ganglion cell layer in a range of elasmobranchs from different depths. The retina is examined for regional specializations for acute vision in six species of selachians, Galeocerdo cuvieri, Hemiscyllium ocellatum, Scyliorhinus canicula, Galeus melastomus, Etmopterus spinax, Isistius brasiliensis, one species of batoid, Raja bigelowi and one species of chimaera, Hydrolagus mirabilis. These species represent a range of lifestyles including pelagic, mesopelagic and benthic habitats, living from shallow water to the sea bottom at a depth of more than 3000 m. The topography of cells within the ganglion cell layer is non-uniform and changes markedly across the retina. Most species possess an increased density of cells across the horizontal (dorsal) meridian or visual streak, with a density range of 500 to 2,500 cells per mm(2) with one or more regional increases in density lying within this specialized horizontal area. It is proposed that the higher spatial resolving power provided by the horizontal streak in these species mediates panoramic vision in the lower frontal visual field. Only I. brasiliensis possesses a concentric arrangement of retinal iso-density contours in temporal retina or an area centralis, thereby increasing spatial resolving power in a more specialized part of the visual field, an adaptation for its unusual feeding behavior. In Nissl-stained material, amacrine and ganglion cell populations could be distinguished on the criteria of soma size, soma shape and nuclear staining. Quantitative analyses show that the proportion of amacrine cells lying within the ganglion cell layer is non-uniform and ranges between 0.4 and 12.3% in specialized retinal areas and between 8.2 and 48.1% in the peripheral non-specialized regions. Analyses of soma area of the total population of cells in the ganglion cell layer also show that the pelagic species possess significantly

  4. Melanopsin retinal ganglion cell loss in Alzheimer's disease

    DEFF Research Database (Denmark)

    La Morgia, Chiara; Ross-Cisneros, Fred N; Koronyo, Yosef

    2015-01-01

    OBJECTIVE: Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer's disease (AD). We investigated mRGCs in AD, hypothesizing their contribution to circadian dysfunction. METHODS: We assessed retinal nerve...

  5. THE MODULATORY ROLE OF TAURINE IN RETINAL GANGLION CELLS

    OpenAIRE

    Jiang, Zheng; Bulley, Simon; Guzzone, Joseph; Ripps, Harris; Shen, Wen

    2013-01-01

    Taurine (2-aminoethylsuphonic acid) is present in nearly all animal tissues, and is the most abundant free amino acid in muscle, heart, CNS and retina. Although it is known to be a major cytoprotectant and essential for normal retinal development, its role in retinal neurotransmission and modulation is not well understood. We investigated the response of taurine in retinal ganglion cells, and its effect on synaptic transmission between ganglion cells and their pre-synaptic neurons. We find th...

  6. Polymodal Sensory Integration in Retinal Ganglion Cells.

    Science.gov (United States)

    Križaj, David

    2016-01-01

    An animal's ability to perceive the external world is conditioned by its capacity to extract and encode specific features of the visual image. The output of the vertebrate retina is not a simple representation of the 2D visual map generated by photon absorptions in the photoreceptor layer. Rather, spatial, temporal, direction selectivity and color "dimensions" of the original image are distributed in the form of parallel output channels mediated by distinct retinal ganglion cell (RGC) populations. We propose that visual information transmitted to the brain includes additional, light-independent, inputs that reflect the functional states of the retina, anterior eye and the body. These may include the local ion microenvironment, glial metabolism and systemic parameters such as intraocular pressure, temperature and immune activation which act on ion channels that are intrinsic to RGCs. We particularly focus on light-independent mechanical inputs that are associated with physical impact, cell swelling and intraocular pressure as excessive mechanical stimuli lead to the counterintuitive experience of "pressure phosphenes" and/or debilitating blinding disease such as glaucoma and diabetic retinopathy. We point at recently discovered retinal mechanosensitive ion channels as examples through which molecular physiology brings together Greek phenomenology, modern neuroscience and medicine. Thus, RGC output represents a unified picture of the embodied context within which vision takes place.

  7. Frequency Responses of Rat Retinal Ganglion Cells.

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    Alex E Hadjinicolaou

    Full Text Available There are 15-20 different types of retinal ganglion cells (RGC in the mammalian retina, each encoding different aspects of the visual scene. The mechanism by which post-synaptic signals from the retinal network generate spikes is determined by each cell's intrinsic electrical properties. Here we investigate the frequency responses of morphologically identified rat RGCs using intracellular injection of sinusoidal current waveforms, to assess their intrinsic capabilities with minimal contributions from the retinal network. Recorded cells were classified according to their morphological characteristics (A, B, C or D-type and their stratification (inner (i, outer (o or bistratified in the inner plexiform layer (IPL. Most cell types had low- or band-pass frequency responses. A2, C1 and C4o cells were band-pass with peaks of 15-30 Hz and low-pass cutoffs above 56 Hz (A2 cells and ~42 Hz (C1 and C4o cells. A1 and C2i/o cells were low-pass with peaks of 10-15 Hz (cutoffs 19-25 Hz. Bistratified D1 and D2 cells were also low-pass with peaks of 5-10 Hz (cutoffs ~16 Hz. The least responsive cells were the B2 and C3 types (peaks: 2-5 Hz, cutoffs: 8-11 Hz. We found no difference between cells stratifying in the inner and outer IPL (i.e., ON and OFF cells or between cells with large and small somas or dendritic fields. Intrinsic physiological properties (input resistance, spike width and sag had little impact on frequency response at low frequencies, but account for 30-40% of response variability at frequencies >30 Hz.

  8. Troxler Fading, Eye Movements, and Retinal Ganglion Cell Properties

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    Romain Bachy

    2014-12-01

    Full Text Available We present four movies demonstrating the effect of flicker and blur on the magnitude and speed of adaptation for foveal and peripheral vision along the three color axes that isolate retinal ganglion cells projecting to magno, parvo, and konio layers of the LGN. The demonstrations support the eye movement hypothesis for Troxler fading for brightness and color, and demonstrate the effects of flicker and blur on adaptation of each class of retinal ganglion cells.

  9. Single-cell resolution imaging of retinal ganglion cell apoptosis in vivo using a cell-penetrating caspase-activatable peptide probe.

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    Xudong Qiu

    Full Text Available Peptide probes for imaging retinal ganglion cell (RGC apoptosis consist of a cell-penetrating peptide targeting moiety and a fluorophore-quencher pair flanking an effector caspase consensus sequence. Using ex vivo fluorescence imaging, we previously validated the capacity of these probes to identify apoptotic RGCs in cell culture and in an in vivo rat model of N-methyl- D-aspartate (NMDA-induced neurotoxicity. Herein, using TcapQ488, a new probe designed and synthesized for compatibility with clinically-relevant imaging instruments, and real time imaging of a live rat RGC degeneration model, we fully characterized time- and dose-dependent probe activation, signal-to-noise ratios, and probe safety profiles in vivo. Adult rats received intravitreal injections of four NMDA concentrations followed by varying TcapQ488 doses. Fluorescence fundus imaging was performed sequentially in vivo using a confocal scanning laser ophthalmoscope and individual RGCs displaying activated probe were counted and analyzed. Rats also underwent electroretinography following intravitreal injection of probe. In vivo fluorescence fundus imaging revealed distinct single-cell probe activation as an indicator of RGC apoptosis induced by intravitreal NMDA injection that corresponded to the identical cells observed in retinal flat mounts of the same eye. Peak activation of probe in vivo was detected 12 hours post probe injection. Detectable fluorescent RGCs increased with increasing NMDA concentration; sensitivity of detection generally increased with increasing TcapQ488 dose until saturating at 0.387 nmol. Electroretinography following intravitreal injections of TcapQ488 showed no significant difference compared with control injections. We optimized the signal-to-noise ratio of a caspase-activatable cell penetrating peptide probe for quantitative non-invasive detection of RGC apoptosis in vivo. Full characterization of probe performance in this setting creates an important in

  10. Melanopsin Ganglion Cells Are the Most Resistant Retinal Ganglion Cell Type to Axonal Injury in the Rat Retina

    OpenAIRE

    Pérez de Sevilla Müller, Luis; Sargoy, Allison; Rodriguez, Allen R.; Brecha, Nicholas C.

    2014-01-01

    We report that the most common retinal ganglion cell type that remains after optic nerve transection is the M1 melanopsin ganglion cell. M1 ganglion cells are members of the intrinsically photosensitive retinal ganglion cell population that mediates non-image-forming vision, comprising ∼2.5% of all ganglion cells in the rat retina. In the present study, M1 ganglion cells comprised 1.7±1%, 28±14%, 55±13% and 82±8% of the surviving ganglion cells 7, 14, 21 and 60 days after optic nerve transect...

  11. Encoding visual information in retinal ganglion cells with prosthetic stimulation

    Science.gov (United States)

    Freeman, Daniel K.; Rizzo, Joseph F., III; Fried, Shelley I.

    2011-06-01

    Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving retinal neurons. The ability to replicate the spatiotemporal pattern of ganglion cell spike trains present under normal viewing conditions is presumably an important factor for restoring high-quality vision. In order to replicate such activity with a retinal prosthesis, it is important to consider both how visual information is encoded in ganglion cell spike trains, and how retinal neurons respond to electric stimulation. The goal of the current review is to bring together these two concepts in order to guide the development of more effective stimulation strategies. We review the experiments to date that have studied how retinal neurons respond to electric stimulation and discuss these findings in the context of known retinal signaling strategies. The results from such in vitro studies reveal the advantages and disadvantages of activating the ganglion cell directly with the electric stimulus (direct activation) as compared to activation of neurons that are presynaptic to the ganglion cell (indirect activation). While direct activation allows high temporal but low spatial resolution, indirect activation yields improved spatial resolution but poor temporal resolution. Finally, we use knowledge gained from in vitro experiments to infer the patterns of elicited activity in ongoing human trials, providing insights into some of the factors limiting the quality of prosthetic vision.

  12. The modulatory role of taurine in retinal ganglion cells.

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    Jiang, Zheng; Bulley, Simon; Guzzone, Joseph; Ripps, Harris; Shen, Wen

    2013-01-01

    Taurine (2-aminoethylsuphonic acid) is present in nearly all animal tissues, and is the most abundant free amino acid in muscle, heart, CNS, and retina. Although it is known to be a major cytoprotectant and essential for normal retinal development, its role in retinal neurotransmission and modulation is not well understood. We investigated the response of taurine in retinal ganglion cells, and its effect on synaptic transmission between ganglion cells and their presynaptic neurons. We find that taurine-elicited currents in ganglion cells could be fully blocked by both strychnine and SR95531, glycine and GABA(A) receptor antagonists, respectively. This suggests that taurine-activated receptors might share the antagonists with GABA and glycine receptors. The effect of taurine at micromolar concentrations can effectively suppress spontaneous vesicle release from the presynaptic neurons, but had limited effects on light-evoked synaptic signals in ganglion cells. We also describe a metabotropic effect of taurine in the suppression of light-evoked response in ganglion cells. Clearly, taurine acts in multiple ways to modulate synaptic signals in retinal output neurons, ganglion cells.

  13. THE MODULATORY ROLE OF TAURINE IN RETINAL GANGLION CELLS

    Science.gov (United States)

    Jiang, Zheng; Bulley, Simon; Guzzone, Joseph; Ripps, Harris; Shen, Wen

    2017-01-01

    Taurine (2-aminoethylsuphonic acid) is present in nearly all animal tissues, and is the most abundant free amino acid in muscle, heart, CNS and retina. Although it is known to be a major cytoprotectant and essential for normal retinal development, its role in retinal neurotransmission and modulation is not well understood. We investigated the response of taurine in retinal ganglion cells, and its effect on synaptic transmission between ganglion cells and their pre-synaptic neurons. We find that taurine-elicited currents in ganglion cells could be fully blocked by both strychnine and SR95531, glycine and GABAA receptor antagonists, respectively. This suggests that taurine-activated receptors might share the antagonists with GABA and glycine receptors. The effect of taurine at micromolar concentrations can effectively suppress spontaneous vesicle release from the pre-synaptic neurons, but had limited effects on light-evoked synaptic signals in ganglion cells. We also describe a metabotropic effect of taurine in the suppression of light-evoked response in ganglion cells. Clearly, taurine acts in multiple ways to modulate synaptic signals in retinal output neurons, ganglion cells. PMID:23392924

  14. Ionic channel changes in glaucomatous retinal ganglion cells: multicompartment modeling.

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    Maturana, Matias I; Turpin, Andrew; McKendrick, Allison M; Kameneva, Tatiana

    2014-01-01

    This research takes a step towards discovering underlying ionic channel changes in the glaucomatous ganglion cells. Glaucoma is characterized by a gradual death of retinal ganglion cells. In this paper, we propose a hypothesis that the ionic channel concentrations change during the progression of glaucoma. We use computer simulation of a multi-compartment morphologically correct model of a mouse retinal ganglion cell to verify our hypothesis. Using published experimental data, we alter the morphology of healthy ganglion cells to replicate glaucomatous cells. Our results suggest that in glaucomatous cell, the sodium channel concentration decreases in the soma by 30% and by 60% in the dendrites, calcium channel concentration decreases by 10% in all compartments, and leak channel concentration increases by 40% in the soma and by 100% in the dendrites.

  15. Processing of natural temporal stimuli by macaque retinal ganglion cells

    NARCIS (Netherlands)

    Hateren, J.H. van; Rüttiger, L.; Lee, B.B.

    2002-01-01

    This study quantifies the performance of primate retinal ganglion cells in response to natural stimuli. Stimuli were confined to the temporal and chromatic domains and were derived from two contrasting environments, one typically northern European and the other a flower show. The performance of the

  16. Regulation of Taurine transporter activity in cultured rat retinal ganglion cells and rat retinal Muller Cells

    International Nuclear Information System (INIS)

    Eissa, Laila A.; Smith, Sylvia B.; El-sherbeny, Amira A.

    2006-01-01

    Diabetic retinopathy is one of the most common complications of diabetes. The amino acid taurine is believed to play an antioxidant protective role in diabetic retinopathy through the scavenging of the reactive species. It is not well established whether taurine uptake is altered in retina cells during diabetic conditions. Thus, the present study was designed to investigate the changes in taurine transport in cultures of rat retinal Muller cells and rat retinal ganglion cells under conditions associated with diabetes. Taurine was abundantly taken up by retinal Muller cells and rat retinal ganglion cells under normal glycemic condition. Taurine was actively transported to rat Muller cells and rat retinal ganglion cells in a Na and Cl dependant manner. Taurine uptake further significantly elevated in both type of cells after the incubation with high glucose concentration. This effect could be attributed to the increase in osmolarity. Because Nitric Oxide (NO) is a molecule implicated in the pathogenesis of diabetes, we also determined the activity of taurine transporter in cultured rat retinal Muller cells and rat retinal ganglion cells in the presence of the NO donors, SIN-1 and SNAP. Taurine uptake was elevated above control value after 24-h incubation with low concentration of NO donors. We finally investigated the ability of neurotoxic glutamate to change taurine transporter activity in both types of cells. Uptake of taurine was significantly increased in rat retinal ganglion cells when only incubated with high concentration of glutamate. Our data provide evidence that taurine transporter is present in cultured rat retinal ganglion and Muller cells and is regulated by hyperosmolarity. The data are relevant to disease such as diabetes and neuronal degeneration where retinal cell volume may dramatically change. (author)

  17. The circadian response of intrinsically photosensitive retinal ganglion cells.

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    Andrew J Zele

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGC signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central or intrinsic (retinal network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18-30 years with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC and outer retina (cone photoreceptors was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux. Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin retinal ganglion cells mediate this circadian variation.

  18. Hypoxia-ischemia and retinal ganglion cell damage

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    Charanjit Kaur

    2008-08-01

    Full Text Available Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling11Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, SingaporeAbstract: Retinal hypoxia is the potentially blinding mechanism underlying a number of sight-threatening disorders including central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease and some types of glaucoma. Hypoxia is implicated in loss of retinal ganglion cells (RGCs occurring in such conditions. RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1α and its target genes such as vascular endothelial growth factor (VEGF and nitric oxide synthase (NOS. Increased production of VEGF results in disruption of the blood retinal barrier leading to retinal edema. Enhanced expression of NOS results in increased production of nitric oxide which may be toxic to the cells resulting in their death. Excess glutamate release in hypoxic-ischemic conditions causes excitotoxic damage to the RGCs through activation of ionotropic and metabotropic glutamate receptors. Activation of glutamate receptors is thought to initiate damage in the retina by a cascade of biochemical effects such as neuronal NOS activation and increase in intracellular Ca2+ which has been described as a major contributing factor to RGC loss. Excess production of proinflammatory cytokines also mediates cell damage. Besides the above, free-radicals generated in hypoxic-ischemic conditions result in RGC loss because of an imbalance between antioxidant- and oxidant-generating systems. Although many advances have been made in understanding the mediators and mechanisms of injury, strategies to improve the damage are lacking. Measures to prevent neuronal injury have to be developed.Keywords: retinal hypoxia, retinal ganglion cells, glutamate receptors, neuronal injury, retina

  19. Retinal Ganglion Cell Loss in Diabetes Associated with Elevated Homocysteine

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    Kenneth S. Shindler

    2009-11-01

    Full Text Available A number of studies have suggested that homocysteine may be a contributing factor to development of retinopathy in diabetic patients based on observed correlations between elevated homocysteine levels and the presence of retinopathy. The significance of such a correlation remains to be determined, and potential mechanisms by which homocysteine might induce retinopathy have not been well characterized. Ganapathy and colleagues1 used mutant mice that have endogenously elevated homocysteine levels due to heterozygous deletion of the cystathionine-β-synthase gene to examine changes in retinal pathology following induction of diabetes. Their finding that elevated homocysteine levels hastens loss of cells in the retinal ganglion cell layer suggests that toxicity to ganglion cells may warrant further investigation as a potential mechanism of homocysteine enhanced susceptibility to diabetic retinopathy.

  20. Intrinsically photosensitive retinal ganglion cell function in relation to age

    DEFF Research Database (Denmark)

    Herbst, Kristina; Sander, Birgit; Lund-Andersen, Henrik

    2012-01-01

    The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim...... of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC....

  1. Veratridine increases the survival of retinal ganglion cells in vitro

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    S.P.F. Pereira

    1997-12-01

    Full Text Available Neuronal cell death is an important phenomenon involving many biochemical pathways. This degenerative event has been studied to understand how the cells activate the mechanisms that lead to self-destruction. Target cells and afferent cells play a relevant role in the regulation of natural cell death. We studied the effect of veratridine (1.5, 3.0, 4.5 and 6.0 µM on the survival of neonatal rat retinal ganglion cells in vitro. Veratridine (3.0 µM, a well-known depolarizing agent that opens the Na+ channel, promoted a two-fold increase in the survival of retinal ganglion cells kept in culture for 48 h. This effect was dose-dependent and was blocked by 1.0 µM tetrodotoxin (a classical voltage-dependent Na+ channel blocker and 30.0 µM flunarizine (a Na+ and Ca2+ channel blocker. These results indicate that electrical activity is also important for the maintenance of retinal ganglion cell survival in vitro

  2. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line

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    Kim Chan

    2007-10-01

    Full Text Available Abstract Background Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5. RGC-5 cells were cultured in a closed hypoxic chamber (5% O2 with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38 and nuclear factor-kappa B (NF-κB were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF, a well-known protective neurotrophin for retinal ganglion cells. Results After 48 hours of hypoxic culture, the LDH assay showed 52.3% cell loss, which was reduced to 25.6% and 30.1% when agmatine and BDNF were administered, respectively. This observed cell loss was due to apoptotic cell death, as established by annexin V and caspase-3 assays. Although total expression of MAPKs and NF-κB was not influenced by hypoxic injury, phosphorylation of these two proteins was increased. Agmatine reduced phosphorylation of JNK and NF-κB, while BDNF suppressed phosphorylation of ERK and p38. Conclusion Our results show that agmatine has neuroprotective effects against hypoxia-induced retinal ganglion cell damage in RGC-5 cells and that its effects may act through the JNK and NF-κB signaling pathways. Our data suggest that agmatine may lead to a novel therapeutic strategy to reduce retinal ganglion cell injury related to hypoxia.

  3. Retinal ganglion cell neuroprotection by an angiotensin II blocker in an ex vivo retinal explant model.

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    White, Andrew J R; Heller, Janosch P; Leung, Johahn; Tassoni, Alessia; Martin, Keith R

    2015-12-01

    An ex vivo organotypic retinal explant model was developed to examine retinal survival mechanisms relevant to glaucoma mediated by the renin angiotensin system in the rodent eye. Eyes from adult Sprague Dawley rats were enucleated immediately post-mortem and used to make four retinal explants per eye. Explants were treated either with irbesartan (10 µM), vehicle or angiotensin II (2 μM) for four days. Retinal ganglion cell density was estimated by βIII tubulin immunohistochemistry. Live imaging of superoxide formation with dihydroethidium (DHE) was performed. Protein expression was determined by Western blotting, and mRNA expression was determined by RT-PCR. Irbesartan (10 µM) almost doubled ganglion cell survival after four days. Angiotensin II (2 µM) reduced cell survival by 40%. Sholl analysis suggested that irbesartan improved ganglion cell dendritic arborisation compared to control and angiotensin II reduced it. Angiotensin-treated explants showed an intense DHE fluorescence not seen in irbesartan-treated explants. Analysis of protein and mRNA expression determined that the angiotensin II receptor At1R was implicated in modulation of the NADPH-dependent pathway of superoxide generation. Angiotensin II blockers protect retinal ganglion cells in this model and may be worth further investigation as a neuroprotective treatment in models of eye disease. © The Author(s) 2015.

  4. High speed coding for velocity by archerfish retinal ganglion cells

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    Kretschmer Viola

    2012-06-01

    Full Text Available Abstract Background Archerfish show very short behavioural latencies in response to falling prey. This raises the question, which response parameters of retinal ganglion cells to moving stimuli are best suited for fast coding of stimulus speed and direction. Results We compared stimulus reconstruction quality based on the ganglion cell response parameters latency, first interspike interval, and rate. For stimulus reconstruction of moving stimuli using latency was superior to using the other stimulus parameters. This was true for absolute latency, with respect to stimulus onset, as well as for relative latency, with respect to population response onset. Iteratively increasing the number of cells used for reconstruction decreased the calculated error close to zero. Conclusions Latency is the fastest response parameter available to the brain. Therefore, latency coding is best suited for high speed coding of moving objects. The quantitative data of this study are in good accordance with previously published behavioural response latencies.

  5. Melanopsin-expressing retinal ganglion cells: implications for human diseases

    DEFF Research Database (Denmark)

    La Morgia, Chiara; Ross-Cisneros, Fred N; Hannibal, Jens

    2011-01-01

    interest on these cells, mainly focused on animal models. Only recently, a few studies have started to address the relevance of the mRGC system in humans and related diseases. We recently discovered that mRGCs resist neurodegeneration in two inherited mitochondrial disorders that cause blindness, i......In the last decade, there was the seminal discovery of melanopsin-expressing retinal ganglion cells (mRGCs) as a new class of photoreceptors that subserve the photoentrainment of circadian rhythms and other non-image forming functions of the eye. Since then, there has been a growing research...

  6. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

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    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  7. Pigment epithelium-derived factor protects retinal ganglion cells

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    Fleenor Debra L

    2007-01-01

    Full Text Available Abstract Background Retinal ganglion cells (RGCs are responsible for the transmission of visual signals to the brain. Progressive death of RGCs occurs in glaucoma and several other retinal diseases, which can lead to visual impairment and blindness. Pigment epithelium-derived factor (PEDF is a potent antiangiogenic, neurotrophic and neuroprotective protein that can protect neurons from a variety of pathologic insults. We tested the effects of PEDF on the survival of cultured adult rat RGCs in the presence of glaucoma-like insults, including cytotoxicity induced by glutamate or withdrawal of trophic factors. Results Cultured adult rat RGCs exposed to glutamate for 3 days showed signs of cytotoxicity and death. The toxic effect of glutamate was concentration-dependent (EC50 = 31 μM. In the presence of 100 μM glutamate, RGC number decreased to 55 ± 4% of control (mean ± SEM, n = 76; P 50 values of 13.6 ng/mL (glutamate and 3.4 ng/mL (trophic factor withdrawal, respectively. At 100 ng/mL, PEDF completely protected the cells from both insults. Inhibitors of the nuclear factor κB (NFκB and extracellular signal-regulated kinases 1/2 (ERK1/2 significantly reduced the protective effects of PEDF. Conclusion We demonstrated that PEDF potently and efficaciously protected adult rat RGCs from glutamate- and trophic factor withdrawal-mediated cytotoxicity, via the activation of the NFκB and ERK1/2 pathways. The neuroprotective effect of PEDF represents a novel approach for potential treatment of retinopathies, such as glaucoma.

  8. Rgcs1, a dominant QTL that affects retinal ganglion cell death after optic nerve crush in mice

    Directory of Open Access Journals (Sweden)

    Schlamp Cassandra L

    2008-07-01

    Full Text Available Abstract Background Intrinsic apoptosis of neuronal somas is one aspect of neurodegenerative diseases that can be influenced by genetic background. Genes that affect this process may act as susceptibility alleles that contribute to the complex genetic nature of these diseases. Retinal ganglion cell death is a defining feature of the chronic and genetically complex neurodegenerative disease glaucoma. Previous studies using an optic nerve crush procedure in inbred mice, showed that ganglion cell resistance to crush was affected by the Mendelian-dominant inheritance of 1–2 predicted loci. To assess this further, we bred and phenotyped a large population of F2 mice derived from a resistant inbred strain (DBA/2J and a susceptible strain (BALB/cByJ. Results Genome wide mapping of the F2 mice using microsatellite markers, detected a single highly significant quantitative trait locus in a 25 cM (58 Mb interval on chromosome 5 (Chr5.loc34-59 cM. No interacting loci were detected at the resolution of this screen. We have designated this locus as Retinal ganglion cell susceptible 1, Rgcs1. In silico analysis of this region revealed the presence of 578 genes or expressed sequence tags, 4 of which are highly expressed in the ganglion cell layer of the mammalian retina, and 2 of which are suspected susceptibility alleles in chronic neurodegenerative diseases. In addition, 25 genes contain 36 known single nucleotide polymorphisms that create nonsynonymous amino acid changes between the two parental strains. Collectively, this analysis has identified 7 potential candidate genes that may affect ganglion cell death. Conclusion The process of ganglion cell death is likely one of the many facets of glaucoma susceptibility. A novel dominant locus has been identified that affects sensitivity of ganglion cells to optic nerve crush. The allele responsible for this sensitivity may also be a susceptibility allele for glaucoma.

  9. Diversity in spatial scope of contrast adaptation among mouse retinal ganglion cells.

    Science.gov (United States)

    Khani, Mohammad Hossein; Gollisch, Tim

    2017-12-01

    Retinal ganglion cells adapt to changes in visual contrast by adjusting their response kinetics and sensitivity. While much work has focused on the time scales of these adaptation processes, less is known about the spatial scale of contrast adaptation. For example, do small, localized contrast changes affect a cell's signal processing across its entire receptive field? Previous investigations have provided conflicting evidence, suggesting that contrast adaptation occurs either locally within subregions of a ganglion cell's receptive field or globally over the receptive field in its entirety. Here, we investigated the spatial extent of contrast adaptation in ganglion cells of the isolated mouse retina through multielectrode-array recordings. We applied visual stimuli so that ganglion cell receptive fields contained regions where the average contrast level changed periodically as well as regions with constant average contrast level. This allowed us to analyze temporal stimulus integration and sensitivity separately for stimulus regions with and without contrast changes. We found that the spatial scope of contrast adaptation depends strongly on cell identity, with some ganglion cells displaying clear local adaptation, whereas others, in particular large transient ganglion cells, adapted globally to contrast changes. Thus, the spatial scope of contrast adaptation in mouse retinal ganglion cells appears to be cell-type specific. This could reflect differences in mechanisms of contrast adaptation and may contribute to the functional diversity of different ganglion cell types. NEW & NOTEWORTHY Understanding whether adaptation of a neuron in a sensory system can occur locally inside the receptive field or whether it always globally affects the entire receptive field is important for understanding how the neuron processes complex sensory stimuli. For mouse retinal ganglion cells, we here show that both local and global contrast adaptation exist and that this diversity in

  10. Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

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    Kirstin B. Langer

    2018-04-01

    Full Text Available Summary: Retinal ganglion cells (RGCs are the projection neurons of the retina and transmit visual information to postsynaptic targets in the brain. While this function is shared among nearly all RGCs, this class of cell is remarkably diverse, comprised of multiple subtypes. Previous efforts have identified numerous RGC subtypes in animal models, but less attention has been paid to human RGCs. Thus, efforts of this study examined the diversity of RGCs differentiated from human pluripotent stem cells (hPSCs and characterized defined subtypes through the expression of subtype-specific markers. Further investigation of these subtypes was achieved using single-cell transcriptomics, confirming the combinatorial expression of molecular markers associated with these subtypes, and also provided insight into more subtype-specific markers. Thus, the results of this study describe the derivation of RGC subtypes from hPSCs and will support the future exploration of phenotypic and functional diversity within human RGCs. : In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes. Keywords: iPSC, retina, retinal ganglion cell, RGC subtype, stem cell, ipRGC, alpha RGC, direction selective RGC, RNA-seq

  11. Methane rescues retinal ganglion cells and limits retinal mitochondrial dysfunction following optic nerve crush.

    Science.gov (United States)

    Wang, Ruobing; Sun, Qinglei; Xia, Fangzhou; Chen, Zeli; Wu, Jiangchun; Zhang, Yuelu; Xu, Jiajun; Liu, Lin

    2017-06-01

    Secondary degeneration is a common event in traumatic central nervous system disorders, which involves neuronal apoptosis and mitochondrial dysfunction. Exogenous methane exerts the therapeutic effects in many organ injury. Our study aims to investigate the potential neuroprotection of methane in a rat model of optic nerve crush (ONC). Adult male Sprague-Dawley rats were subjected to ONC and administrated intraperitoneally with methane-saturated or normal saline (10 ml/kg) once per day for one week after ONC. The retinal ganglion cells (RGCs) density was assessed by hematoxylin and eosin staining and Fluoro-Gold retrogradely labeling. Visual function was evaluated by flash visual evoked potentials (FVEP). The retinal apoptosis was measured by terminal-deoxy-transferase-mediated dUTP nick end labeling (TUNEL) assay and the expression of apoptosis-related factors, such as phosphorylated Bcl-2-associated death promoter (pBAD), phosphorylated glycogen synthase kinase-3β (pGSK-3β), Bcl-2 associated X protein (Bax) and Bcl-2 extra large (Bcl-xL). Retinal mitochondrial function was assessed by the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), the mitochondrial DNA (mtDNA) copy number, citrate synthase activity and ATP content. Methane treatment significantly improved the RGC loss and visual dysfunction following ONC. As expected, methane also remarkably inhibited the retinal neural apoptosis, such as the fewer TUNEL-positive cells in ganglion cell layer, accompanied by the up-regulations of anti-apoptotic factors (pGSK-3β, pBAD, Bcl-xL) and the down-regulation of pro-apoptotic factor (Bax). Furthermore, methane treatment suppressed up-regulations of critical mitochondrial components (PGC-1α, NRF1 and TFAM) mRNA and mtDNA copy number, as well as improved the reduction of functional mitochondria markers, including citrate synthase

  12. Retinal ganglion cells: Energetics, compartmentation, axonal transport, cytoskeletons and vulnerability.

    Science.gov (United States)

    Yu, Dao-Yi; Cringle, Stephen J; Balaratnasingam, Chandrakumar; Morgan, William H; Yu, Paula K; Su, Er-Ning

    2013-09-01

    Retinal ganglion cells (RGCs) are specialized projection neurons that relay an immense amount of visual information from the retina to the brain. RGC signal inputs are collected by dendrites and output is distributed from the cell body via very thin (0.5-1 μm) and long (∼50 mm) axons. The RGC cell body is larger than other retinal neurons, but is still only a very small fraction (one ten thousandths) of the length and total surface area of the axon. The total distance traversed by RGCs extends from the retina, starting from synapses with bipolar and amacrine cells, to the brain, to synapses with neurons in the lateral geniculate nucleus. This review will focus on the energy demands of RGCs and the relevant tissues that surround them. RGC survival and function unexceptionally depends upon free energy, predominantly adenosine triphosphate (ATP). RGC energy metabolism is vastly different when compared to that of the photoreceptors. Each subcellular component of the RGC is remarkably different in terms of structure, function and extracellular environment. The energy demands and distribution of each component are also distinct as evidenced by the uneven distribution of mitochondria and ATP within the RGC - signifying the presence of intracellular energy gradients. In this review we will describe RGCs as having four subcellular components, (1) Dendrites, (2) Cell body, (3) Non-myelinated axon, including intraocular and optic nerve head portions, and (4) Myelinated axon, including the intra-orbital and intracranial portions. We will also describe how RGCs integrate information from each subcellular component in order achieve intracellular homeostatic stability as well as respond to perturbations in the extracellular environment. The possible cellular mechanisms such as axonal transport and axonal cytoskeleton proteins that are involved in maintaining RGC energy homeostasis during normal and disease conditions will also be discussed in depth. The emphasis of this

  13. Starburst cells nondirectionally facilitate the responses of direction-selective retinal ganglion cells.

    Science.gov (United States)

    Chiao, Chuan-Chin; Masland, Richard H

    2002-12-15

    The mechanism of direction selectivity in retinal ganglion cells remains controversial. An important issue is how the starburst amacrine cells, which are known to provide a major synaptic input to the direction-selective ganglion cells, participate in the directional discrimination. Here, we present evidence that the cholinergic outputs of the starburst cells affect the responses of the ganglion cells symmetrically; they provide a feedforward excitation that facilitates the response of the ganglion cells to movement in both the preferred and null directions. This seems to place a constraint on models of the directional discrimination in which the starburst cells participate, namely, that their cholinergic synapses be nondirectional in their effects on the ganglion cells.

  14. Displaced retinal ganglion cells in albino and pigmented rats

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    Francisco Manuel Nadal-Nicolás

    2014-10-01

    Full Text Available We have studied in parallel the population of displaced retinal ganglion cells (dRGCs and normally placed (orthotopic RGCs, oRGCs in albino and pigmented rats. Using retrograde tracing from the optic nerve, from both superior colliculi (SC or from the ipsilateral SC in conjunction with Brn3 and melanopsin immunodetection, we report for the first time their total number and topography as well as the number and distribution of those dRGCs and oRGCs that project ipsi- or contralaterally and/or that express any of the three Brn3 isoforms or melanopsin. The total number of RGCs (oRGCs+dRGCs is 84,706±1,249 in albino and 90,440±2,236 in pigmented, out of which 2,383 and 2,428 are melanopsin positive (m-RGCs, respectively. Regarding dRGCs: i/ albino rats have a significantly lower number of dRGCs than pigmented animals (0.5% of the total number of RGCs vs. 2.5%, respectively, ii/ dRGCs project massively to the contralateral SC, iii/ the percentage of ipsilaterality is higher for dRGCs than for oRGCs, iv/ a higher proportion of ipsilateral dRGCs is observed in albino than pigmented animals, v/ dRGC topography is very specific, they predominate in the equatorial temporal retina, being densest where the oRGCs are densest, vi/ Brn3a detects all dRGCs except half of the ipsilateral ones and those that express melanopsin, vii/ the proportion of dRGCs that express Brn3b or Brn3c is slightly lower than in the oRGC population, viii/ a higher percentage of dRGCs (13% albino, 9% pigmented than oRGCs (2.6% express melanopsin, ix/ few m-RGCs (displaced and orthotopic project to the ipsilateral SC, x/ the topography of m-dRGCs does not resemble the general distribution of dRGCs, xi/ The soma size in m-oRGCs ranges from 10 to 21 µm and in m-dRGCs from 8 to 15 µm, xii/ oRGCs and dRGCs have the same susceptibility to axonal injury and hypertension. Although the role of mammalian dRGCs remains to be determined, our data suggest that they are not misplaced by an

  15. Uptake of Retrograde Tracers by Intact Optic Nerve Axons: A New Way to Label Retinal Ganglion Cells

    OpenAIRE

    Liang, Yu-Xiang; Yang, Jian; Yuan, Ti-Fei; So, Kwok-Fai

    2015-01-01

    Retrograde labelling of retinal ganglion cells with optic nerve transection often leads to degeneration of ganglion cells in prolonged experiments. Here we report that an intact optic nerve could uptake retrograde tracers applied onto the surface of the nerve, leading to high efficiency labelling of ganglion cells in the retina with long-term survival of cells. This method labelled a similar number of ganglion cells (2289 +/- 174 at 2 days) as the retrograde labeling technique from the superi...

  16. Strychnine, but not PMBA, inhibits neuronal nicotinic acetylcholine receptors expressed by rabbit retinal ganglion cells.

    Science.gov (United States)

    Renna, J M; Strang, C E; Amthor, F R; Keyser, K T

    2007-01-01

    Strychnine is considered a selective competitive antagonist of glycine gated Cl- channels (Saitoh et al., 1994) and studies have used strychnine at low micromolar concentrations to study the role of glycine in rabbit retina (Linn, 1998; Protti et al., 2005). However, other studies have shown that strychnine, in the concentrations commonly used, is also a potent competitive antagonist of alpha7 nicotinic acetylcholine receptors (nAChRs; Matsubayashi et al., 1998). We tested the effects of low micromolar concentrations of strychnine and 3-[2'-phosphonomethyl[1,1'-biphenyl]-3-yl] alanine (PMBA), a specific glycine receptor blocker (Saitoh et al., 1994; Hosie et al., 1999) on the activation of both alpha7 nAChRs on retinal ganglion cells and on ganglion cell responses to a light flash. Extracellular recordings were obtained from ganglion cells in an isolated retina/choroid preparation and 500 microM choline was used as an alpha7 agonist (Alkondon et al., 1997). We recorded from brisk sustained and brisk transient OFF cells, many of which have been previously shown to have alpha7 receptors (Strang et al., 2005). Further, we tested the effect of strychnine, PMBA and alpha-bungarotoxin on the binding of tetramethylrhodamine alpha-bungarotoxin in the inner plexiform layer. Our data indicates that strychnine, at doses as low as 1.0 microM, can inhibit the alpha7 nAChR-mediated response to choline, but PMBA at concentrations as high as 0.4 microM does not. Binding studies show strychnine and alpha-bungarotoxin inhibit binding of labeled alpha-bungarotoxin in the IPL. Thus, the effects of strychnine application may be to inhibit glycine receptors expressed by ganglion cell or to inhibit amacrine cell alpha7 nAChRs, both of which would result in an increase in the ganglion cell responses. Further research will be required to disentangle the effects of strychnine previously believed to be caused by a single mechanism of glycine receptor inhibition.

  17. Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

    Science.gov (United States)

    Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

    2016-04-01

    Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

  18. Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance

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    Jeffery Glen

    2008-05-01

    Full Text Available Abstract Background The transcription factor Pax6 is expressed by many cell types in the developing eye. Eyes do not form in homozygous loss-of-function mouse mutants (Pax6Sey/Sey and are abnormally small in Pax6Sey/+ mutants. Eyes are also abnormally small in PAX77 mice expressing multiple copies of human PAX6 in addition to endogenous Pax6; protein sequences are identical in the two species. The developmental events that lead to microphthalmia in PAX77 mice are not well-characterised, so it is not clear whether over- and under-expression of Pax6/PAX6 cause microphthalmia through similar mechanisms. Here, we examined the consequences of over-expression for the eye and its axonal connections. Results Eyes form in PAX77+/+ embryos but subsequently degenerate. At E12.5, we found no abnormalities in ocular morphology, retinal cell cycle parameters and the incidence of retinal cell death. From E14.5 on, we observed malformations of the optic disc. From E16.5 into postnatal life there is progressively more severe retinal dysplasia and microphthalmia. Analyses of patterns of gene expression indicated that PAX77+/+ retinae produce a normal range of cell types, including retinal ganglion cells (RGCs. At E14.5 and E16.5, quantitative RT-PCR with probes for a range of molecules associated with retinal development showed only one significant change: a slight reduction in levels of mRNA encoding the secreted morphogen Shh at E16.5. At E16.5, tract-tracing with carbocyanine dyes in PAX77+/+ embryos revealed errors in intraretinal navigation by RGC axons, a decrease in the number of RGC axons reaching the thalamus and an increase in the proportion of ipsilateral projections among those RGC axons that do reach the thalamus. A survey of embryos with different Pax6/PAX6 gene dosage (Pax6Sey/+, Pax6+/+, PAX77+ and PAX77+/+ showed that (1 the total number of RGC axons projected by the retina and (2 the proportions that are sorted into the ipsilateral and

  19. The role of NgR-Rhoa-Rock signal pathway in retinal ganglion cell apoptosis of early diabetic rats

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    Yun-Jie Fu

    2014-09-01

    Full Text Available AIM: To study the function and mechanism of the NgR-Rhoa-Rock signal pathways which exists in the retinal ganglion cells apoptosis in diabetes mellitus(DMrats. METHODS: Some healthy SD rats were operated by means of single intraperitoneal injection of 1% streptozotocin based on the standard of 50mg/kg wight, after that the blood sugar value was greater than 16.7mmol/L as DM model, then randomly divided into 3 groups, each group was 10 rats. In addition to take 10 healthy SD rats as control group. Four groups of rats were bilaterally eyeball intravitreal injection in turn with NgR-siRNA virus 10μL(siRNA group, NgR-siRNA virus diluted 10μL(DM group, NgR-siRNA virus-negative-control solution 10μL(siRNA blank group, NgR-siRNA virus diluted 10μL(normal control group, and fed normally. During that time, some life indexes like blood glucose, body mass, etc. were measured and recorded. After 12wk, the expression of NgR and Rhoa, HE staining, and TUNNEL staining were detected by Western blot analysis. RESULTS: Western blot analysis: compared with normal control group, the expression of NgR and Rhoa in DM group and siRNA blank group increased significantly(PP>0.05; compared with DM group and siRNA blank group, the expression of those proteins significantly lowered in siRNA group. HE staining: compared with normal control group, some extent ganglion cells arranged disorder, irregular shape, spacing not consistent were all found in three groups of model rats; compared with DM group and siRNA blank group, there was some improvement in siRNA group of ganglion cells about the order and shape size. TUNEL staining: compared with normal control group, there were retinal ganglion cells apoptosis in all of three groups of model rats. Compared with DM group and siRNA blank group, the number of retinal ganglion cells apoptotic cells was less, and the shape of cells had improved significantly in siRNA group. CONCLUSION: In the DM phase, the expression of NgR and

  20. Hypothermia Protects and Prolongs the Tolerance Time of Retinal Ganglion Cells against Ischemia.

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    Maximilian Schultheiss

    Full Text Available Hypothermia has been shown to be neuroprotective in the therapy of ischemic stroke in the brain. To date no studies exist on the level of the inner retina and it is unclear if hypothermia would prolong the ischemic tolerance time of retinal ganglion cells, which are decisive in many ischemic retinopathies.Bovine eyes were enucleated and stored either at 21°C or 37°C for 100 or 340 minutes, respectively. Afterwards the globes were dissected, the retina was prepared and either the spontaneous ganglion cell responses were measured or the retina was incubated as an organotypic culture for additional 24 hours. After incubation the retina was either processed for histology (H&E and DAPI staining or real-time PCR (Thy-1 expression was performed.Hypothermia prolonged ganglion cell survival up to 340 minutes under ischemic conditions. In contrast to eyes kept at 37°C the eyes stored at 21°C still showed spontaneous ganglion cell spiking (56.8% versus 0%, a 5.8 fold higher Thy-1 mRNA expression (not significant, but a trend and a preserved retinal structure after 340 minutes of ischemia.Hypothermia protects retinal ganglion cells against ischemia and prolongs their ischemic tolerance time.

  1. Loss of Melanopsin-Expressing Retinal Ganglion Cells in Patients With Diabetic Retinopathy

    DEFF Research Database (Denmark)

    Obara, Elisabeth Anne; Hannibal, Jens; Heegaard, Steffen

    2017-01-01

    Purpose: Photo-entrainment of the circadian clock is mediated by melanopsin-expressing retinal ganglion cells (mRGCs) located in the retina. Patients suffering from diabetic retinopathy (DR) show impairment of light regulated circadian activity such as sleep disorders, altered blood pressure...

  2. Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies

    DEFF Research Database (Denmark)

    La Morgia, C; Ross-Cisneros, F.N.; Sadun, A.A.

    2010-01-01

    Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retina...

  3. Brimonidine prevents axonal and somatic degeneration of retinal ganglion cell neurons

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    Crish Samuel D

    2011-01-01

    Full Text Available Abstract Background Brimonidine is a common drug for lowering ocular pressure and may directly protect retinal ganglion cells in glaucoma. The disease involves early loss of retinal ganglion cell transport to brain targets followed by axonal and somatic degeneration. We examined whether brimonidine preserves ganglion cell axonal transport and abates degeneration in rats with elevated ocular pressure induced by laser cauterization of the episcleral veins. Results Ocular pressure was elevated unilaterally by 90% for a period of 8 weeks post- cauterization. During this time, brimonidine (1mg/kg/day or vehicle (phosphate-buffered saline was delivered systemically and continuously via subcutaneous pump. Animals received bilateral intravitreal injections of fluorescent cholera toxin subunit β (CTB two days before sacrifice to assess anterograde transport. In retinas from the vehicle group, elevated pressure induced a 44% decrease in the fraction of ganglion cells with intact uptake of CTB and a 14-42% reduction in the number of immuno-labelled ganglion cell bodies, with the worst loss occurring nasally. Elevated pressure also caused a 33% loss of ganglion cell axons in vehicle optic nerves and a 70% decrease in CTB transport to the superior colliculus. Each of these components of ganglion cell degeneration was either prevented or significantly reduced in the brimonidine treatment group. Conclusions Continuous and systemic treatment with brimonidine by subcutaneous injection significantly improved retinal ganglion cell survival with exposure to elevated ocular pressure. This effect was most striking in the nasal region of the retina. Brimonidine treatment also preserved ganglion cell axon morphology, sampling density and total number in the optic nerve with elevated pressure. Consistent with improved outcome in the optic projection, brimonidine also significantly reduced the deficits in axonal transport to the superior colliculus associated with

  4. Retinal Ganglion Cell Distribution and Spatial Resolving Power in Deep-Sea Lanternfishes (Myctophidae)

    KAUST Repository

    De Busserolles, Fanny

    2014-01-01

    Topographic analyses of retinal ganglion cell density are very useful in providing information about the visual ecology of a species by identifying areas of acute vision within the visual field (i.e. areas of high cell density). In this study, we investigated the neural cell distribution in the ganglion cell layer of a range of lanternfish species belonging to 10 genera. Analyses were performed on wholemounted retinas using stereology. Topographic maps were constructed of the distribution of all neurons and both ganglion and amacrine cell populations in 5 different species from Nissl-stained retinas using cytological criteria. Amacrine cell distribution was also examined immunohistochemically in 2 of the 5 species using anti-parvalbumin antibody. The distributions of both the total neuron and the amacrine cell populations were aligned in all of the species examined, showing a general increase in cell density toward the retinal periphery. However, when the ganglion cell population was topographically isolated from the amacrine cell population, which comprised up to 80% of the total neurons within the ganglion cell layer, a different distribution was revealed. Topographic maps of the true ganglion cell distribution in 18 species of lanternfishes revealed well-defined specializations in different regions of the retina. Different species possessed distinct areas of high ganglion cell density with respect to both peak density and the location and/or shape of the specialized acute zone (i.e. elongated areae ventro-temporales, areae temporales and large areae centrales). The spatial resolving power was calculated to be relatively low (varying from 1.6 to 4.4 cycles per degree), indicating that myctophids may constitute one of the less visually acute groups of deep-sea teleosts. The diversity in retinal specializations and spatial resolving power within the family is assessed in terms of possible ecological functions and evolutionary history.

  5. A model for the receptive field of retinal ganglion cells.

    Science.gov (United States)

    Cho, Myoung Won; Choi, M Y

    2014-01-01

    Most retina ganglion cells have center-surround receptive fields, where the center may be either ON or OFF while the surround is the opposite. We clarify the functional roles of the receptive field structure, on the basis of the modern theory of natural data processing. It is suggested that the retina shares the principal mechanism and performance of image processing with a video codec in computers, where the antagonism in spatial or temporal receptive fields originates from the orthogonality condition between linear filters for optimal coding of visual signals. We also reveal what visual information is multiplexed across the discharges of an ensemble of ganglion cells. Our theory makes it possible to predict the cross-correlations between ganglion cell spikes, which are optimized for LGN cells to respond accurately and quickly to their receptive fields. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Dendritic maturation in cat retinal ganglion cells: a Lucifer yellow study.

    Science.gov (United States)

    Dann, J F; Buhl, E H; Peichl, L

    1987-09-11

    The dendritic morphology of developing cat alpha- and beta-retinal ganglion cells was investigated by intracellular injection of Lucifer yellow. In both cell classes the basic pattern of adult morphology was present at birth. However, the presence of transient small spiny protrusions along the dendrites was characteristic of early postnatal cells. Many alpha-cells were further distinguished by a small degree of dendritic bi-stratification which disappeared within the first 5 postnatal days. Therefore during the period before the eyes opened (P7-P10) there was a considerable degree of modification and maturation in dendritic morphology in both classes of retinal ganglion cells. alpha- and beta-cells exhibited differing temporal patterns of dendritic growth, which argues against a 'passive-stretching' hypothesis that explains dendritic field enlargement solely as an effect of retinal areal growth.

  7. Msx2 alters the timing of retinal ganglion cells fate commitment and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Shao-Yun, E-mail: jiangshaoyun@yahoo.com [School of Dentistry, Tianjin Medical University, 12 Qi Xiang Tai Street, Tianjin 300070 (China); Wang, Jian-Tao, E-mail: wangjiantao65@hotmail.com [Eye Center, Tianjin Medical University, 64 Tongan Road, Tianjin 300070 (China); Dohney Eye Institute, Keck School of Medicine, University of Southern California, 1355 San Pablo Street, DOH 314, Los Angeles, CA 90033 (United States)

    2010-05-14

    Timing of cell fate commitment determines distinct retinal cell types, which is believed to be controlled by a tightly coordinated regulatory program of proliferation, cell cycle exit and differentiation. Although homeobox protein Msx2 could induce apoptosis of optic vesicle, it is unclear whether Msx2 regulates differentiation and cell fate commitment of retinal progenitor cells (RPCs) to retinal ganglion cells (RGCs). In this study, we show that overexpression of Msx2 transiently suppressed the expression of Cyclin D1 and blocked cell proliferation. Meanwhile, overexpression of Msx2 delayed the expression of RGC-specific differentiation markers (Math5 and Brn3b), which showed that Msx2 could affect the timing of RGCs fate commitment and differentiation by delaying the timing of cell cycle exit of retinal progenitors. These results indicate Msx2 possesses dual regulatory functions in controlling cell cycle progression of retinal RPCs and timing of RGCs differentiation.

  8. Retinal Ganglion Cell Loss in X-linked Adrenoleukodystrophy with anABCD1Mutation (Gly266Arg).

    Science.gov (United States)

    Ohkuma, Yasuhiro; Hayashi, Takaaki; Yoshimine, Syouyou; Tsuneoka, Hiroshi; Terao, Yoko; Akiyama, Masaharu; Ida, Hiroyuki; Ohashi, Toya; Okumura, Akihisa; Ebihara, Nobuyuki; Murakami, Akira; Shimozawa, Nobuyuki

    2014-01-01

    The authors here report a single case of a 10-year-old male patient who presented with severe vision loss associated with progressive demyelination. The patient was diagnosed with X-linked childhood cerebral adrenoleukodystrophy (ALD). Genetic analysis demonstrated a missense mutation (Gly266Arg) in exon 1 of the ABCD1 gene. His corrected visual acuity confirmed the absolute lack of light perception in both eyes. Funduscopy revealed severe pallor of the optic disc in both eyes. Spectral-domain optical coherence tomography showed thinning of the retinal ganglion cell and inner plexiform layers (GCL and IPL). Thinning of the GCL and IPL may be due to transneuronal retrograde degeneration of ganglion cells secondary to optic tract demyelination.

  9. Electrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons.

    Science.gov (United States)

    Maturana, Matias I; Apollo, Nicholas V; Garrett, David J; Kameneva, Tatiana; Cloherty, Shaun L; Grayden, David B; Burkitt, Anthony N; Ibbotson, Michael R; Meffin, Hamish

    2018-02-01

    Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell's spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear.

  10. Correspondence between visual and electrical input filters of ON and OFF mouse retinal ganglion cells

    Science.gov (United States)

    Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

    2017-08-01

    Objective. Over the past two decades retinal prostheses have made major strides in restoring functional vision to patients blinded by diseases such as retinitis pigmentosa. Presently, implants use single pulses to activate the retina. Though this stimulation paradigm has proved beneficial to patients, an unresolved problem is the inability to selectively stimulate the on and off visual pathways. To this end our goal was to test, using white noise, voltage-controlled, cathodic, monophasic pulse stimulation, whether different retinal ganglion cell (RGC) types in the wild type retina have different electrical input filters. This is an important precursor to addressing pathway-selective stimulation. Approach. Using full-field visual flash and electrical and visual Gaussian noise stimulation, combined with the technique of spike-triggered averaging (STA), we calculate the electrical and visual input filters for different types of RGCs (classified as on, off or on-off based on their response to the flash stimuli). Main results. Examining the STAs, we found that the spiking activity of on cells during electrical stimulation correlates with a decrease in the voltage magnitude preceding a spike, while the spiking activity of off cells correlates with an increase in the voltage preceding a spike. No electrical preference was found for on-off cells. Comparing STAs of wild type and rd10 mice revealed narrower electrical STA deflections with shorter latencies in rd10. Significance. This study is the first comparison of visual cell types and their corresponding temporal electrical input filters in the retina. The altered input filters in degenerated rd10 retinas are consistent with photoreceptor stimulation underlying visual type-specific electrical STA shapes in wild type retina. It is therefore conceivable that existing implants could target partially degenerated photoreceptors that have only lost their outer segments, but not somas, to selectively activate the on and off

  11. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, S.S.; Lyerly, D.P. (Environmental Protection Agency, Research Triangle Park, NC (USA))

    1989-12-01

    Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with (35S)methionine and (3H)fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm-treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13-day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure.

  12. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells

    International Nuclear Information System (INIS)

    Padilla, S.S.; Lyerly, D.P.

    1989-01-01

    Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with [35S]methionine and [3H]fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm-treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13-day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure

  13. Co-expression of two subtypes of melatonin receptor on rat M1-type intrinsically photosensitive retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Wen-Long Sheng

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGCs are involved in circadian and other non-image forming visual responses. An open question is whether the activity of these neurons may also be under the regulation mediated by the neurohormone melatonin. In the present work, by double-staining immunohistochemical technique, we studied the expression of MT1 and MT2, two known subtypes of mammalian melatonin receptors, in rat ipRGCs. A single subset of retinal ganglion cells labeled by the specific antibody against melanopsin exhibited the morphology typical of M1-type ipRGCs. Immunoreactivity for both MT1 and MT2 receptors was clearly seen in the cytoplasm of all labeled ipRGCs, indicating that these two receptors were co-expressed in each of these neurons. Furthermore, labeling for both the receptors were found in neonatal M1 cells as early as the day of birth. It is therefore highly plausible that retinal melatonin may directly modulate the activity of ipRGCs, thus regulating non-image forming visual functions.

  14. Retinal vessel diameters decrease with macular ganglion cell layer thickness in autosomal dominant optic atrophy and in healthy subjects

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Grønskov, Karen; Larsen, Michael

    2014-01-01

    diameters (central retinal artery equivalent, CRAE, and central retinal vein equivalent, CRVE). Statistical analysis was corrected for age, gender, spherical equivalent refraction, axial length and mean arterial blood pressure (MABP) in a mixed model analysis. RESULTS: Retinal arteries and veins were...... ganglion cell-inner plexiform layer (GC-IPL) thickness (p = 0.0017 and p = 0.0057, respectively). CONCLUSION: Narrow retinal arteries and veins were associated not only with the severity of ADOA but with ganglion cell volume in patients with ADOA and in healthy subjects. This suggests that narrow vessels...

  15. Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity

    Science.gov (United States)

    Morin, Lawrence P.; Blanchard, Jane H.; Provencio, Ignacio

    2003-01-01

    The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. Copyright 2003 Wiley-Liss, Inc.

  16. Neuroprotective Effect of Lutein on NMDA-Induced Retinal Ganglion Cell Injury in Rat Retina.

    Science.gov (United States)

    Zhang, Chanjuan; Wang, Zhen; Zhao, Jiayi; Li, Qin; Huang, Cuiqin; Zhu, Lihong; Lu, Daxiang

    2016-05-01

    Lutein injection is a possible therapeutic approach for retinal diseases, but the molecular mechanism of its neuroprotective effect remains to be elucidated. The aim of this study was to investigate its protective effects in retinal ganglion cells (RGCs) against N-methyl-D-aspartate (NMDA)-induced retinal damage in vivo. Retinal damage was induced by intravitreal NMDA injection in rats. Each animal was given five daily intraperitoneal injections of Lutein or vehicle along with intravitreal NMDA injections. Electroretinograms were recorded. The number of viable RGCs was quantified using the retinal whole-mount method by immunofluorescence. Proteins were measured by Western blot assays. Lutein reduced the retinal damage and improved the response to light, as shown by an animal behavior assay (the black-and-white box method) in rats. Furthermore, Lutein treatment prevented the NMDA-induced reduction in phNR wave amplitude. Lutein increased RGC number after NMDA-induced retina damage. Most importantly, Bax, cytochrome c, p-p38 MAPK, and p-c-Jun were all upregulated in rats injected with NMDA, but these expression patterns were reversed by continuous Lutein uptake. Bcl-2, p-GSK-3β, and p-Akt in the Lutein-treated eyes were increased compared with the NMDA group. Lutein has neuroprotective effects against retinal damage, its protective effects may be partly mediated by its anti-excitability neurotoxicity, through MAPKs and PI3K/Akt signaling, suggesting a potential approach for suppressing retinal neural damage.

  17. Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey

    DEFF Research Database (Denmark)

    Hannibal, J; Kankipati, L; Strang, C E

    2014-01-01

    Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are entrained to the environmental light/dark cycle via intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin and the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP......-expressing cells characterized as inner and outer stratifying melanopsin RGCs. Two macaque monkeys were anesthetized and received a unilateral intravitreal injection of CtB. Bilateral retinal projections containing colocalized CtB and PACAP immunostaining were identified in the SCN, the lateral geniculate complex...

  18. Retinal ganglion cell topography and spatial resolving power in the white rhinoceros (Ceratotherium simum).

    Science.gov (United States)

    Coimbra, João Paulo; Manger, Paul R

    2017-08-01

    This study sought to determine whether the retinal organization of the white rhinoceros (Ceratotherium simum), a large African herbivore with lips specialized for grazing in open savannahs, relates to its foraging ecology and habitat. Using stereology and retinal wholemounts, we estimated a total of 353,000 retinal ganglion cells. Their density distribution reveals an unusual topographic organization of a temporal (2,000 cells/mm 2 ) and a nasal (1,800 cells/mm 2 ) area embedded within a well-defined horizontal visual streak (800 cells/mm 2 ), which is remarkably similar to the retinal organization in the black rhinoceros. Alpha ganglion cells comprise 3.5% (12,300) of the total population of ganglion cells and show a similar distribution pattern with maximum densities also occurring in the temporal (44 cells/mm 2 ) and nasal (40 cells/mm 2 ) areas. We found higher proportions of alpha cells in the dorsal and ventral retinas. Given their role in the detection of brisk transient stimuli, these higher proportions may facilitate the detection of approaching objects from the front and behind while grazing with the head at 45 °. Using ganglion cell peak density and eye size (29 mm, axial length), we estimated upper limits of spatial resolving power of 7 cycles/deg (temporal area), 6.6 cycles/deg (nasal area), and 4.4 cycles/deg (horizontal streak). The resolution of the temporal area potentially assists with grazing, while the resolution of the streak may be used for panoramic surveillance of the horizon. The nasal area may assist with detection of approaching objects from behind, potentially representing an adaptation compensating for limited neck and head mobility. J. Comp. Neurol., 525:2484-2498, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Visual Field Defects and Retinal Ganglion Cell Losses in Human Glaucoma Patients

    Science.gov (United States)

    Harwerth, Ronald S.; Quigley, Harry A.

    2007-01-01

    Objective The depth of visual field defects are correlated with retinal ganglion cell densities in experimental glaucoma. This study was to determine whether a similar structure-function relationship holds for human glaucoma. Methods The study was based on retinal ganglion cell densities and visual thresholds of patients with documented glaucoma (Kerrigan-Baumrind, et al.) The data were analyzed by a model that predicted ganglion cell densities from standard clinical perimetry, which were then compared to histologic cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of ganglion cell densities associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs. measured cell densities had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs. measured values was 2.59 dB, the mean and SD of the distribution of residual errors of prediction was -0.26 ± 3.22 dB. Conclusions Visual field defects by standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis of interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease. PMID:16769839

  20. The effect of morphology upon electrophysiological responses of retinal ganglion cells: simulation results.

    Science.gov (United States)

    Maturana, Matias I; Kameneva, Tatiana; Burkitt, Anthony N; Meffin, Hamish; Grayden, David B

    2014-04-01

    Retinal ganglion cells (RGCs) display differences in their morphology and intrinsic electrophysiology. The goal of this study is to characterize the ionic currents that explain the behavior of ON and OFF RGCs and to explore if all morphological types of RGCs exhibit the phenomena described in electrophysiological data. We extend our previous single compartment cell models of ON and OFF RGCs to more biophysically realistic multicompartment cell models and investigate the effect of cell morphology on intrinsic electrophysiological properties. The membrane dynamics are described using the Hodgkin - Huxley type formalism. A subset of published patch-clamp data from isolated intact mouse retina is used to constrain the model and another subset is used to validate the model. Two hundred morphologically distinct ON and OFF RGCs are simulated with various densities of ionic currents in different morphological neuron compartments. Our model predicts that the differences between ON and OFF cells are explained by the presence of the low voltage activated calcium current in OFF cells and absence of such in ON cells. Our study shows through simulation that particular morphological types of RGCs are capable of exhibiting the full range of phenomena described in recent experiments. Comparisons of outputs from different cells indicate that the RGC morphologies that best describe recent experimental results are ones that have a larger ratio of soma to total surface area.

  1. Glia-Neuron Interactions in the Retina Can Be Studied in Cocultures of Muller Cells and Retinal Ganglion Cells

    DEFF Research Database (Denmark)

    Skytt, D. M.; Toft-Kehler, A. K.; Braendstrup, C. T.

    2016-01-01

    Glia-neuron partnership is important for inner retinal homeostasis and any disturbances may result in retinal ganglion cell (RGC) death. Müller cells support RGCs with essential functions such as removing excess glutamate and providing energy sources. The aim was to explore the impact of Müller c...

  2. Role of retinal glial cell glutamate transporters in retinal ganglion cell survival following stimulation of NMDA receptor.

    Science.gov (United States)

    Furuya, Toshie; Pan, Zhiying; Kashiwagi, Kenji

    2012-03-01

    To investigate the role of glutamate transporters (GLTs)in retinal glial cells that were treated with N-methyl-D-aspartate (NMDA), in retinal ganglion cell (RGC) survival. Primary cultures of retinal glial cells or RGCs from 3-day-old Sprague-Dawley rats were employed in the present study. Retinal glial cells were treated with NMDA and changes in GLT mRNA and protein expression were analyzed. The effects of pretreating retinal glial cells with the GLAST-specific inhibitor, rottlerin (ROT), and the GLT-1-specific inhibitor, dihydrokainic acid (DHK), on RGC survival were investigated under exposure to NMDA. The amount of glutamate in the culture medium of retinal glial cells was measured by high-performance liquid chromatography. NMDA treatment increased GLAST and GLT-1 expression. GLAST and GLT-1 mRNA expression increased by 2.94-fold and 3.36-fold at 12 h after treatment with the highest concentration of NMDA (33 mM), and by 1.41-fold and 1.39-fold at 24 h, respectively. GLT-1 and GLAST protein expression also increased. MK801, an NMDA-receptor antagonist, inhibited the NMDA-induced upregulation of GLT mRNA expression. Co-culture with retinal glial cells increased the survival rate of RGCs. ROT decreased the survival rate of RGCs, whereas DHK significantly increased the survival rate of RGCs treated with 33 mM NMDA. NMDA treatment reduced the total amount of glutamate in the culture medium, particularly when 33 mM NMDA was added to the medium. ROT pretreatment increased the amount of glutamate in the culture medium, whereas DHK pretreatment decreased it. GLAST and GLT-1 may have different roles in the survival of RGCs mediated by retinal glial cells. These results suggest that the NMDA-associated induction of GLTs plays an important role in RGC survival.

  3. A Novel Retinal Ganglion Cell Promoter for Utility in AAV Vectors

    Directory of Open Access Journals (Sweden)

    Killian S. Hanlon

    2017-09-01

    Full Text Available Significant advances in gene therapy have enabled exploration of therapies for inherited retinal disorders, many of which are in preclinical development or clinical evaluation. Gene therapy for retinal conditions has led the way in this growing field. The loss of retinal ganglion cells (RGCs is a hallmark of a number of retinal disorders. As the field matures innovations that aid in refining therapies and optimizing efficacy are in demand. Gene therapies under development for RGC-related disorders, when delivered with recombinant adeno associated vectors (AAV, have typically been expressed from ubiquitous promoter sequences. Here we describe how a novel promoter from the murine Nefh gene was selected to drive transgene expression in RGCs. The Nefh promoter, in an AAV2/2 vector, was shown to drive preferential EGFP expression in murine RGCs in vivo following intravitreal injection. In contrast, EGFP expression from a CMV promoter was observed not only in RGCs, but throughout the inner nuclear layer and in amacrine cells located within the ganglion cell layer (GCL. Of note, the Nefh promoter sequence is sufficiently compact to be readily accommodated in AAV vectors, where transgene size represents a significant constraint. Moreover, this promoter should in principle provide a more targeted and potentially safer alternative for RGC-directed gene therapies.

  4. Spatially and Temporally Regulated NRF2 Gene Therapy Using Mcp-1 Promoter in Retinal Ganglion Cell Injury

    Directory of Open Access Journals (Sweden)

    Kosuke Fujita

    2017-06-01

    Full Text Available Retinal ganglion cell degeneration triggered by axonal injury is believed to underlie many ocular diseases, including glaucoma and optic neuritis. In these diseases, retinal ganglion cells are affected unevenly, both spatially and temporally, such that healthy and unhealthy cells coexist in different patterns at different time points. Herein, we describe a temporally and spatially regulated adeno-associated virus gene therapy aiming to reduce undesired off-target effects on healthy retinal neurons. The Mcp-1 promoter previously shown to be activated in stressed retinal ganglion cells following murine optic nerve injury was combined with the neuroprotective intracellular transcription factor Nrf2. In this model, Mcp-1 promoter-driven NRF2 expression targeting only stressed retinal ganglion cells showed efficacy equivalent to non-selective cytomegalovirus promoter-driven therapy for preventing cell death. However, cytomegalovirus promoter-mediated NRF2 transcription induced cellular stress responses and death of Brn3A-positive uninjured retinal ganglion cells. Such undesired effects were reduced substantially by adopting the Mcp-1 promoter. Combining a stress-responsive promoter and intracellular therapeutic gene is a versatile approach for specifically targeting cells at risk of degeneration. This strategy may be applicable to numerous chronic ocular and non-ocular conditions.

  5. Seasonally Changing Cryptochrome 1b Expression in the Retinal Ganglion Cells of a Migrating Passerine Bird.

    Directory of Open Access Journals (Sweden)

    Christine Nießner

    Full Text Available Cryptochromes, blue-light absorbing proteins involved in the circadian clock, have been proposed to be the receptor molecules of the avian magnetic compass. In birds, several cryptochromes occur: Cryptochrome 2, Cryptochrome 4 and two splice products of Cryptochrome 1, Cry1a and Cry1b. With an antibody not distinguishing between the two splice products, Cryptochrome 1 had been detected in the retinal ganglion cells of garden warblers during migration. A recent study located Cry1a in the outer segments of UV/V-cones in the retina of domestic chickens and European robins, another migratory species. Here we report the presence of cryptochrome 1b (eCry1b in retinal ganglion cells and displaced ganglion cells of European Robins, Erithacus rubecula. Immuno-histochemistry at the light microscopic and electron microscopic level showed eCry1b in the cell plasma, free in the cytosol as well as bound to membranes. This is supported by immuno-blotting. However, this applies only to robins in the migratory state. After the end of the migratory phase, the amount of eCry1b was markedly reduced and hardly detectable. In robins, the amount of eCry1b in the retinal ganglion cells varies with season: it appears to be strongly expressed only during the migratory period when the birds show nocturnal migratory restlessness. Since the avian magnetic compass does not seem to be restricted to the migratory phase, this seasonal variation makes a role of eCry1b in magnetoreception rather unlikely. Rather, it could be involved in physiological processes controlling migratory restlessness and thus enabling birds to perform their nocturnal flights.

  6. Scene from above: retinal ganglion cell topography and spatial resolving power in the giraffe (Giraffa camelopardalis).

    Science.gov (United States)

    Coimbra, João Paulo; Hart, Nathan S; Collin, Shaun P; Manger, Paul R

    2013-06-15

    The giraffe (Giraffa camelopardalis) is a browser that uses its extensible tongue to selectively collect leaves during foraging. As the tallest extant terrestrial mammal, its elevated head height provides panoramic surveillance of the environment. These aspects of the giraffe's ecology and phenotype suggest that vision is of prime importance. Using Nissl-stained retinal wholemounts and stereological methods, we quantitatively assessed the retinal specializations in the ganglion cell layer of the giraffe. The mean total number of retinal ganglion cells was 1,393,779 and their topographic distribution revealed the presence of a horizontal visual streak and a temporal area. With a mean peak of 14,271 cells/mm(2), upper limits of spatial resolving power in the temporal area ranged from 25 to 27 cycles/degree. We also observed a dorsotemporal extension (anakatabatic area) that tapers toward the nasal retina giving rise to a complete dorsal arch. Using neurofilament-200 immunohistochemistry, we also detected a dorsal arch formed by alpha ganglion cells with density peaks in the temporal (14-15 cells/mm(2)) and dorsonasal (10 cells/mm(2)) regions. As with other artiodactyls, the giraffe shares the presence of a horizontal streak and a temporal area which, respectively, improve resolution along the horizon and in the frontal visual field. The dorsal arch is related to the giraffe's head height and affords enhanced resolution in the inferior visual field. The alpha ganglion cell distribution pattern is unique to the giraffe and enhances acquisition of motion information for the control of tongue movement during foraging and the detection of predators. Copyright © 2012 Wiley Periodicals, Inc.

  7. Retinal ganglion cell analysis in multiple sclerosis and optic neuritis

    DEFF Research Database (Denmark)

    Britze, Josefine; Pihl-Jensen, Gorm; Frederiksen, Jette Lautrup

    2017-01-01

    in MS patients both with and without previous ON compared to healthy controls. GCL thinning was associated with visual function in most studies (n = 10) and expanded disability status scale (EDSS) scores (n = 6). In acute ON, thinning of the GCL is measurable prior to RNFL thinning, and GCL thickness......, studies showed significant thinning of the GCL within the first 5 weeks (n = 5), earlier than retinal nerve fibre layer (RNFL) thinning. GCL thinning at 1-2 months after acute ON predicted visual function at 6 months (n = 3). The meta-analysis showed that the thickness of the GCL was significantly reduced...... after 1-2 months may predict visual function after 6 months. Furthermore, GCL thinning occurs in MS both with and without prior ON, and may be associated with visual function and EDSS score. This suggests that the GCL is a promising biomarker, which may be used to examine in vivo neurodegeneration...

  8. Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice

    Directory of Open Access Journals (Sweden)

    Schlamp Cassandra L

    2007-03-01

    Full Text Available Abstract Background Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal ganglion cells. Since ganglion cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect ganglion cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to ganglion cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured ganglion cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for ganglion cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the cell death phenotype. Results Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. Conclusion Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving

  9. The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation.

    Science.gov (United States)

    Xie, Laiqing; Cheng, Long; Xu, Guoxu; Zhang, Ji; Ji, Xiaoyan; Song, E

    2017-06-10

    Excessive Ultra violet (UV) radiation induces injuries to retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates UV-induced cell death. In this study, we show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted shRNAs. Compound 19 almost blocked UV-induced p53-Cyp-D mitochondrial association, mPTP opening and subsequent cytochrome C release. Further studies showed that compound 19 inhibited UV-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage. Together, compound 19 protects RPEs and RGCs from UV radiation, possibly via silencing Cyp-D-regulated intrinsic mitochondrial death pathway. Compound 19 could a lead compound for treating UV-associated retinal degeneration diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Cellular Origin of Spontaneous Ganglion Cell Spike Activity in Animal Models of Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    David J. Margolis

    2011-01-01

    Full Text Available Here we review evidence that loss of photoreceptors due to degenerative retinal disease causes an increase in the rate of spontaneous ganglion spike discharge. Information about persistent spike activity is important since it is expected to add noise to the communication between the eye and the brain and thus impact the design and effective use of retinal prosthetics for restoring visual function in patients blinded by disease. Patch-clamp recordings from identified types of ON and OFF retinal ganglion cells in the adult (36–210 d old rd1 mouse show that the ongoing oscillatory spike activity in both cell types is driven by strong rhythmic synaptic input from presynaptic neurons that is blocked by CNQX. The recurrent synaptic activity may arise in a negative feedback loop between a bipolar cell and an amacrine cell that exhibits resonant behavior and oscillations in membrane potential when the normal balance between excitation and inhibition is disrupted by the absence of photoreceptor input.

  11. Calpain Inhibition Attenuates Apoptosis of Retinal Ganglion Cells in Acute Optic Neuritis

    Science.gov (United States)

    Smith, Amena W.; Das, Arabinda; Guyton, M. Kelly; Ray, Swapan K.; Rohrer, Baerbel

    2011-01-01

    Purpose. Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with the pathogenesis of multiple sclerosis (MS) and is initiated by the attack of autoreactive T cells against self-myelin antigens, resulting in demyelination, degeneration of retinal ganglion cells (RGCs), and cumulative visual impairment. Methods. Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats on day 0, and animals received daily intraperitoneal injections of calpain inhibitor (calpeptin) or vehicle from day 1 until killed. Retinal cell death was analyzed by DNA fragmentation, and surviving ganglion cells were quantified after double labeling of retinal tissue with TUNEL and Brn3a. The expression of apoptotic and inflammatory proteins was determined by Western blotting. Results. It was demonstrated that calpain inhibition downregulates expression of proapoptotic proteins and the proinflammatory molecule nuclear factor-kappa B (NF-κB) in the retina of Lewis rats with acute EAE. Immunofluorescent labeling revealed that apoptotic cells in the RGC layer of vehicle-treated EAE animals were Brn3a positive, and a moderate dose of calpeptin dramatically reduced the frequency of apoptotic RGCs. Conclusions. These results suggest that calpain inhibition might be a useful supplement to immunomodulatory therapies such as corticosteroids in ON, due to its neuroprotective effect on RGCs. PMID:21613375

  12. Topographic prominence discriminator for the detection of short-latency spikes of retinal ganglion cells

    Science.gov (United States)

    Choi, Myoung-Hwan; Ahn, Jungryul; Park, Dae Jin; Lee, Sang Min; Kim, Kwangsoo; Cho, Dong-il Dan; Senok, Solomon S.; Koo, Kyo-in; Goo, Yong Sook

    2017-02-01

    Objective. Direct stimulation of retinal ganglion cells in degenerate retinas by implanting epi-retinal prostheses is a recognized strategy for restoration of visual perception in patients with retinitis pigmentosa or age-related macular degeneration. Elucidating the best stimulus-response paradigms in the laboratory using multielectrode arrays (MEA) is complicated by the fact that the short-latency spikes (within 10 ms) elicited by direct retinal ganglion cell (RGC) stimulation are obscured by the stimulus artifact which is generated by the electrical stimulator. Approach. We developed an artifact subtraction algorithm based on topographic prominence discrimination, wherein the duration of prominences within the stimulus artifact is used as a strategy for identifying the artifact for subtraction and clarifying the obfuscated spikes which are then quantified using standard thresholding. Main results. We found that the prominence discrimination based filters perform creditably in simulation conditions by successfully isolating randomly inserted spikes in the presence of simple and even complex residual artifacts. We also show that the algorithm successfully isolated short-latency spikes in an MEA-based recording from degenerate mouse retinas, where the amplitude and frequency characteristics of the stimulus artifact vary according to the distance of the recording electrode from the stimulating electrode. By ROC analysis of false positive and false negative first spike detection rates in a dataset of one hundred and eight RGCs from four retinal patches, we found that the performance of our algorithm is comparable to that of a generally-used artifact subtraction filter algorithm which uses a strategy of local polynomial approximation (SALPA). Significance. We conclude that the application of topographic prominence discrimination is a valid and useful method for subtraction of stimulation artifacts with variable amplitudes and shapes. We propose that our algorithm

  13. Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma.

    Science.gov (United States)

    Song, Wei-tao; Zhang, Xue-yong; Xia, Xiao-bo

    2015-05-01

    Glaucoma is one of the leading eye diseases resulting in blindness due to the death of retinal ganglion cells. This study aimed to develop novel protocol to promote the differentiation of retinal Müller cells into ganglion cells in vivo in a rat model of glaucoma. The stem cells dedifferentiated from rat retinal Müller cells were randomized to receive transfection with empty lentivirus PGC-FU-GFP or lentivirus PGC-FU-Atoh7-GFP, or no transfection. The stem cells were induced further to differentiate. Ocular hypertension was induced using laser photocoagulation. The eyes were injected with Atoh7 expression vector lentivirus PGC-FU-Atoh7-GFP. Eyeball frozen sections, immunohistochemistry, RT-PCR, Western bolt, and apoptosis assay were performed. We found that the proportion of ganglion cells differentiated from Atoh7-tranfected stem cells was significantly higher than that of the other two groups. The mean intraocular pressure of glaucomatous eyes was elevated significantly compared with those of contralateral eyes. Some retinal Müller cells in the inner nuclear layer entered the mitotic cell cycle in rat chronic ocular hypertension glaucoma model. Atoh7 contributes to the differentiation of retinal Müller cells into retinal ganglion cells in rat model of glaucoma. In conclusion, Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma, thus opening up a new avenue for gene therapy and optic nerve regeneration in glaucoma. © 2015 by the Society for Experimental Biology and Medicine.

  14. The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β and TNF-α

    International Nuclear Information System (INIS)

    Salles von-Held-Ventura, Juliana; Mázala-de-Oliveira, Thalita; Cândida da Rocha Oliveira, Amanda; Granja, Marcelo Gomes; Gonçalves-de-Albuquerque, Cassiano Felippe; Castro-Faria-Neto, Hugo Caire; Giestal-de-Araujo, Elizabeth

    2016-01-01

    Ouabain is a steroid hormone that binds to the enzyme Na + , K + – ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1β and TNF-α are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1β and TNF-α also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1β and TNF-α could be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1β or anti-TNF-α antibodies. In agreement, IL-1β or TNF-α increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-α and IL-1β from retinal cell cultures. Interestingly, TNF-α and IL-1β regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF-α and IL-1β signaling pathways leading to an increase in retinal ganglion cell survival. - Highlights: • Pro-inflammatory cytokines regulates the ouabain effect on RGC survival. • Ouabain treatment modulates the intracellular levels of TNF-α and IL-1β. • Ouabain induces the release of TNF-α and IL-1β in retinal cell cultures.

  15. The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β and TNF-α

    Energy Technology Data Exchange (ETDEWEB)

    Salles von-Held-Ventura, Juliana; Mázala-de-Oliveira, Thalita; Cândida da Rocha Oliveira, Amanda; Granja, Marcelo Gomes [Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ (Brazil); Gonçalves-de-Albuquerque, Cassiano Felippe; Castro-Faria-Neto, Hugo Caire [Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Departamento de Fisiologia e Farmacodinâmica, Av., no 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ (Brazil); Giestal-de-Araujo, Elizabeth, E-mail: egiestal@vm.uff.br [Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2016-09-09

    Ouabain is a steroid hormone that binds to the enzyme Na{sup +}, K{sup +} – ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1β and TNF-α are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1β and TNF-α also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1β and TNF-α could be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1β or anti-TNF-α antibodies. In agreement, IL-1β or TNF-α increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-α and IL-1β from retinal cell cultures. Interestingly, TNF-α and IL-1β regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF-α and IL-1β signaling pathways leading to an increase in retinal ganglion cell survival. - Highlights: • Pro-inflammatory cytokines regulates the ouabain effect on RGC survival. • Ouabain treatment modulates the intracellular levels of TNF-α and IL-1β. • Ouabain induces the release of TNF-α and IL-1β in retinal cell cultures.

  16. Retinal ganglion cells electrophysiology: the effect of cell morphology on impulse waveform.

    Science.gov (United States)

    Maturana, Matias I; Wong, Raymond; Cloherty, Shaun L; Ibbotson, Michael R; Hadjinicolaou, Alex E; Grayden, David B; Burkitt, Anthony N; Meffin, Hamish; O'Brien, Brendan J; Kameneva, Tatiana

    2013-01-01

    There are 16 morphologically defined classes of rats retinal ganglion cells (RGCs). Using computer simulation of a realistic anatomically correct A1 mouse RGC, we investigate the effect of the cell's morphology on its impulse waveform, using the first-, and second-order time derivatives as well as the phase plot features. Using whole cell patch clamp recordings, we recorded the impulse waveform for each of the rat RGCs types. While we found some clear differences in many features of the impulse waveforms for A2 and B2 cells compared to other cell classes, many cell types did not show clear differences.

  17. Investigation of retinal ganglion cells and axons of normal rats using fluorogold retrograde labeling

    International Nuclear Information System (INIS)

    Yin Xiaolei; Ye Jian; Chen Chunlin

    2006-01-01

    To investigate the retinal ganglion cells (RGCs) by means of fluorogold retrograde labeling, RGCs were labeled by injecting the fluorogold bilaterally into the superficial superior colliculus and lateral genicutate nucleus in six adult SD rats. One and two weeks (3 rats in each group) after injecting the fluorogold, RGCs FG-labeled were observed and the number of them were counted. The results showed that after a week mean density of fluorogold-labeled RGCs was 2210 ± 128/mm 2 , and it was 2164 ± 117/mm 2 after two weeks. Our conclusion is fluorogold retrograde labeling could be very useful in the research of RGCs. (authors)

  18. A Pixel-Encoder Retinal Ganglion Cell with Spatially Offset Excitatory and Inhibitory Receptive Fields

    OpenAIRE

    Keith P. Johnson; Lei Zhao; Daniel Kerschensteiner

    2018-01-01

    The spike trains of retinal ganglion cells (RGCs) are the only source of visual information to the brain. Here, we genetically identify an RGC type in mice that functions as a pixel encoder and increases firing to light increments (PixON-RGC). PixON-RGCs have medium-sized dendritic arbors and non-canonical center-surround receptive fields. From their receptive field center, PixON-RGCs receive only excitatory input, which encodes contrast and spatial information linearly. From their receptive ...

  19. Protection of pattern electroretinogram and retinal ganglion cells by oncostatin M after optic nerve injury.

    Directory of Open Access Journals (Sweden)

    Xin Xia

    Full Text Available Injury to retinal ganglion cell (RGC axons leads to selective loss of RGCs and vision. Previous studies have shown that exogenous neurotrophic factors promote RGC survival. We investigated the neuroprotective effects of oncostatin M (OSM, a member of the IL-6 family of cytokines, on pattern electroretinogram (PERG and RGC survival after optic nerve crush (ON-crush in the mouse. BALB/C mice received ON-crush in the left eyes for either 4-second or 1-second duration (4-s or 1-s. Fluoro-gold retrograde labeling was used to identify RGCs. RGC function was assessed by PERG measurement. OSM or CNTF protein was injected intravitreally immediately after ON-crush. OSM responsive cells were identified by localization of increased STAT3 phosphorylation. Significant higher RGC survival (46% of untreated control was seen in OSM-treated eyes when assessed 2 weeks after 4-s ON-crush as compared to that (14% of untreated control of the PBS-treated eyes (P<0.001. In addition, PERG amplitude was significantly higher in eyes treated with OSM or CNTF 1 week after 1-s ON-crush (36% of baseline as compared with the amplitude of PBS-treated eyes (19% of the baseline, P = 0.003. An increase in STAT3 phosphorylation was localized in Müller layer after OSM treatment, suggesting that Müller cells mediate the effect of OSM. Our results demonstrate that one single injection of either OSM or CNTF after ON-crush improves RGC survival together with their electrophysiological activity. These data provide proof-of-concept for using neurotrophic factors OSM and CNTF for RGC degenerative diseases, including glaucoma and acute optic nerve trauma.

  20. Multicompartment retinal ganglion cells response to high frequency bi-phasic pulse train stimulation: Simulation results.

    Science.gov (United States)

    Maturana, Matias I; Grayden, David B; Burkitt, Anthony N; Meffin, Hamish; Kameneva, Tatiana

    2013-01-01

    Retinal ganglion cells (RGCs) are the sole output neurons of the retina that carry information about a visual scene to the brain. By stimulating RGCs with electrical stimulation, it is possible to elicit a sensation of light for people with macular degeneration or retinitis pigmentosa. To investigate the responses of RGCs to high frequency bi-phasic pulse train stimulation, we use previously constrained models of multi-compartment OFF RGCs. The morphologies of mouse RGCs are taken from the Chalupa set of the NeuroMorpho database. The cell models are divided into compartments representing the dendrites, soma and axon that vary between the cells. A total of 132 cells are simulated in the NEURON environment. Results show that the cell morphology plays an important role in the response characteristics of the cell to high frequency bi-phasic pulse train stimulation.

  1. Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration

    Directory of Open Access Journals (Sweden)

    Valeria Colafrancesco

    2011-01-01

    Full Text Available The aim of this study was to investigate the effect of nerve growth factor (NGF administration on retinal ganglion cells (RGCs in experimentally induced glaucoma (GL and diabetic retinopathy (DR. GL was induced in adult rats by injection of hypertonic saline into the episcleral vein of the eye and diabetes (DT was induced by administration of streptozoticin. Control and experimental rats were treated daily with either ocular application of NGF or vehicle solution. We found that both animal models present a progressive degeneration of RGCs and changing NGF and VEGF levels in the retina and optic nerve. We then proved that NGF eye drop administration exerts a protective effect on these models of retinal degeneration. In brief, our findings indicate that NGF can play a protective role against RGC degeneration occurring in GL and DR and suggest that ocular NGF administration might be an effective pharmacological approach.

  2. Melanopsin retinal ganglion cells are not labeled in Thy-1YFP-16 transgenic mice.

    Science.gov (United States)

    Grillo, Stephanie L; Stella, Salvatore L

    2018-01-17

    Retinal ganglion cells (RGCs) that express the photopigment melanopsin (mRGCs) are photosensitive and initiate the non-image-forming pathway, where the majority of their axons terminate in the suprachiasmatic nucleus (SCN). RGCs only make up approximately half of the cells in the ganglion cell layer of the retina; therefore, it is important to be able to distinguish them from other cell types. The transgenic Thy-1 YFP mouse line 16 (Thy-1 YFP-16) expresses yellow-fluorescent protein (YFP) in projection neurons, including RGCs. Our objective was to determine whether mRGCs are labeled with YFP in Thy-1 YFP-16 transgenic mice. Paraformaldehyde-fixed retinal wholemounts and frozen vertical sections were prepared from Thy-1 YFP-16 mice and fluorescently labeled with rabbit anti-melanopsin and guinea-pig anti-RNA binding protein with multiple splicing to identify mRGCs and total RGCs, respectively. Thy-1 YFP-16 mouse brains were sectioned coronally and imaged to view RGC axonal projections to the SCN. Confocal images of retinal preparations show that the majority (∼89%) of mRGCs are not YFP-positive in Thy-1 YFP-16 mice, where ∼11% expressed a weak fluorescent signal. In addition, there are almost no YFP-positive axons present in the SCN of coronal brain sections. We conclude that the majority of mRGC somas and axons are not labeled with YFP in the transgenic Thy-1 YFP-16 mouse line; therefore, this mouse model may not suitable for research involving mRGC visual pathways.

  3. Characterization of Ca2+ Signalling in Postnatal Mouse Retinal Ganglion Cells: Involvement of OPA1 in Ca2+ Clearance

    Czech Academy of Sciences Publication Activity Database

    Dayanithi, Govindan; Chen-Kuo-Chang, M.; Viero, C.; Hamel, C.; Muller, A.; Lenaers, G.

    2010-01-01

    Roč. 31, č. 2 (2010), s. 53-65 ISSN 1381-6810 Institutional research plan: CEZ:AV0Z50390703 Keywords : retinal ganglion cells * Ca2+ homeostasis * Ca2+ clearance Subject RIV: FH - Neurology Impact factor: 1.333, year: 2010

  4. The ciliary margin zone of the mammalian retina generates retinal ganglion cells

    Science.gov (United States)

    Marcucci, Florencia; Murcia-Belmonte, Veronica; Coca, Yaiza; Ferreiro-Galve, Susana; Wang, Qing; Kuwajima, Takaaki; Khalid, Sania; Ross, M. Elizabeth; Herrera, Eloisa; Mason, Carol

    2016-01-01

    Summary The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live-imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. As Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2−/− mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity. PMID:28009286

  5. The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells.

    Science.gov (United States)

    Marcucci, Florencia; Murcia-Belmonte, Veronica; Wang, Qing; Coca, Yaiza; Ferreiro-Galve, Susana; Kuwajima, Takaaki; Khalid, Sania; Ross, M Elizabeth; Mason, Carol; Herrera, Eloisa

    2016-12-20

    The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. Because Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2 -/- mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2 + cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Characterization of spontaneous excitatory synaptic currents in salamander retinal ganglion cells.

    Science.gov (United States)

    Taylor, W R; Chen, E; Copenhagen, D R

    1995-01-01

    1. Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded under voltage-clamp conditions. Consistent with activation of non-NMDA-type glutamate receptors, the sEPSCs reversed at potentials above 0 mV, were blocked by 1 microM CNQX and prolonged by 2 mM aniracetam. 2. The peak conductance of the averaged sEPSCs (n = 70-400) was 130 +/- 60 pS (mean +/- S.D.; 17 cells, ranging from 70 to 290 pS). Amplitude distributions were skewed towards larger amplitudes. 3. The decay of individual and mean sEPSCs was exponential with a mean time constant (tau d) of 3.75 +/- 0.84 ms (n = 13), which was voltage independent. The 10-90% rise time of the sEPSCs was 1.30 +/- 0.44 ms (n = 13). There was no correlation between sEPSC rise time and tau d suggesting that dendritic filtering alone did not shape the time course of sEPSCs. 4. Light-evoked EPSCs in these retinal ganglion cells are mediated by concomitant activation of NMDA and non-NMDA receptors; however, no NMDA component was discerned in the sEPSCs, even when recording at -96 mV in Mg(2+)-free solutions. The decay time course was not altered by 20 microM AP7, an NMDA antagonist, nor was an NMDA component unmasked by adding glycine or D-serine. These results suggest that NMDA and non-NMDA receptors are not coactivated by a single vesicle of transmitter during spontaneous release, and thus are probably not colocalized in the postsynaptic membrane at the sites of spontaneous release. 5. The sEPSCs were an order of magnitude faster than the non-NMDA receptor-mediated EPSCs evoked by light stimuli, and it is proposed that the EPSC time course is determined largely by the extended time course of release of synaptic vesicles from bipolar cells. The quantal content of a light-evoked non-NMDA receptor-mediated EPSC in an on-off cell is about 200 quanta. Images Figure 6 PMID:7562636

  7. Longitudinal in vivo imaging of retinal ganglion cells and retinal thickness changes following optic nerve injury in mice.

    Directory of Open Access Journals (Sweden)

    Balwantray C Chauhan

    Full Text Available Retinal ganglion cells (RGCs die in sight-threatening eye diseases. Imaging RGCs in humans is not currently possible and proof of principle in experimental models is fundamental for future development. Our objective was to quantify RGC density and retinal thickness following optic nerve transection in transgenic mice expressing cyan fluorescent protein (CFP under control of the Thy1 promoter, expressed by RGCs and other neurons.A modified confocal scanning laser ophthalmoscopy (CSLO/spectral-domain optical coherence tomography (SD-OCT camera was used to image and quantify CFP+ cells in mice from the B6.Cg-Tg(Thy1-CFP23Jrs/J line. SD-OCT circle (1 B-scan, raster (37 B-scans and radial (24 B-scans scans of the retina were also obtained. CSLO was performed at baseline (n = 11 and 3 (n = 11, 5 (n = 4, 7 (n = 10, 10 (n = 6, 14 (n = 7 and 21 (n = 5 days post-transection, while SD-OCT was performed at baseline and 7, 14 and 35 days (n = 9 post-transection. Longitudinal change in CFP+ cell density and retinal thickness were computed. Compared to baseline, the mean (SD percentage CFP+ cells remaining at 3, 5, 7, 10, 14 and 21 days post-transection was 86 (9%, 63 (11%, 45 (11%, 31 (9%, 20 (9% and 8 (4%, respectively. Compared to baseline, the mean (SD retinal thickness at 7 days post-transection was 97 (3%, 98 (2% and 97 (4% for the circle, raster and radial scans, respectively. The corresponding figures at 14 and 35 days post-transection were 96 (3%, 97 (2% and 95 (3%; and 93 (3%, 94 (3% and 92 (3%.Longitudinal imaging showed an exponential decline in CFP+ cell density and a small (≤8% reduction in SD-OCT measured retinal thickness post-transection. SD-OCT is a promising tool for detecting structural changes in experimental optic neuropathy. These results represent an important step towards translation for clinical use.

  8. Eliminating Glutamatergic Input onto Horizontal Cells Changes the Dynamic Range and Receptive Field Organization of Mouse Retinal Ganglion Cells.

    Science.gov (United States)

    Ströh, Sebastian; Puller, Christian; Swirski, Sebastian; Hölzel, Maj-Britt; van der Linde, Lea I S; Segelken, Jasmin; Schultz, Konrad; Block, Christoph; Monyer, Hannah; Willecke, Klaus; Weiler, Reto; Greschner, Martin; Janssen-Bienhold, Ulrike; Dedek, Karin

    2018-02-21

    In the mammalian retina, horizontal cells receive glutamatergic inputs from many rod and cone photoreceptors and return feedback signals to them, thereby changing photoreceptor glutamate release in a light-dependent manner. Horizontal cells also provide feedforward signals to bipolar cells. It is unclear, however, how horizontal cell signals also affect the temporal, spatial, and contrast tuning in retinal output neurons, the ganglion cells. To study this, we generated a genetically modified mouse line in which we eliminated the light dependency of feedback by deleting glutamate receptors from mouse horizontal cells. This genetic modification allowed us to investigate the impact of horizontal cells on ganglion cell signaling independent of the actual mode of feedback in the outer retina and without pharmacological manipulation of signal transmission. In control and genetically modified mice (both sexes), we recorded the light responses of transient OFF-α retinal ganglion cells in the intact retina. Excitatory postsynaptic currents (EPSCs) were reduced and the cells were tuned to lower temporal frequencies and higher contrasts, presumably because photoreceptor output was attenuated. Moreover, receptive fields of recorded cells showed a significantly altered surround structure. Our data thus suggest that horizontal cells are responsible for adjusting the dynamic range of retinal ganglion cells and, together with amacrine cells, contribute to the center/surround organization of ganglion cell receptive fields in the mouse. SIGNIFICANCE STATEMENT Horizontal cells represent a major neuronal class in the mammalian retina and provide lateral feedback and feedforward signals to photoreceptors and bipolar cells, respectively. The mode of signal transmission remains controversial and, moreover, the contribution of horizontal cells to visual processing is still elusive. To address the question of how horizontal cells affect retinal output signals, we recorded the light

  9. Modeling activity and target-dependent developmental cell death of mouse retinal ganglion cells ex vivo.

    Directory of Open Access Journals (Sweden)

    Sylvie Voyatzis

    Full Text Available Programmed cell death is widespread during the development of the central nervous system and serves multiple purposes including the establishment of neural connections. In the mouse retina a substantial reduction of retinal ganglion cells (RGCs occurs during the first postnatal week, coinciding with the formation of retinotopic maps in the superior colliculus (SC. We previously established a retino-collicular culture preparation which recapitulates the progressive topographic ordering of RGC projections during early post-natal life. Here, we questioned whether this model could also be suitable to examine the mechanisms underlying developmental cell death of RGCs. Brn3a was used as a marker of the RGCs. A developmental decline in the number of Brn3a-immunolabelled neurons was found in the retinal explant with a timing that paralleled that observed in vivo. In contrast, the density of photoreceptors or of starburst amacrine cells increased, mimicking the evolution of these cell populations in vivo. Blockade of neural activity with tetrodotoxin increased the number of surviving Brn3a-labelled neurons in the retinal explant, as did the increase in target availability when one retinal explant was confronted with 2 or 4 collicular slices. Thus, this ex vivo model reproduces the developmental reduction of RGCs and recapitulates its regulation by neural activity and target availability. It therefore offers a simple way to analyze developmental cell death in this classic system. Using this model, we show that ephrin-A signaling does not participate to the regulation of the Brn3a population size in the retina, indicating that eprhin-A-mediated elimination of exuberant projections does not involve developmental cell death.

  10. Research progress on protecting effect of taurine on retinal ganglion cells

    Directory of Open Access Journals (Sweden)

    Zong-Li Hu

    2014-03-01

    Full Text Available Taurine is a common amino acid in almost all kinds of tissues of animals. Several researches have pointed out that taurine is essential for protecting retinal ganglion cells(RGCs. The mechanisms are summarized as follows: 1Reducing the NMDA-induced RGC excitotoxicity 2Regulating the function of Müller cells 3Protecting function of mitochondria 4Stimulating regeneration of the optic nerve 5Promoting accommodative regulation 6Improving the microcirculation of retina. Glaucoma is one kind of ophthalmopathy leading to apoptosis of RGCs. Recently, taurine has been proved to be effective in protecting the RGC in several aspects, both in vitro and vivo experiments. This indicates a potential treatment of optic nerve in glaucoma or other ophthalmic diseases.

  11. Synchronized Firings in Retinal Ganglion Cells in Response to Natural Stimulation

    International Nuclear Information System (INIS)

    Zhang Ying-Ying; Xiao Lei; Liu Wen-Zhong; Gong Hai-Qing; Liang Pei-Ji

    2011-01-01

    The response of synchronously firing groups of population retinal ganglion cells (RGCs) to natural movies (NMs) and pseudo-random white-noise checker-board flickering (CB, as control) are investigated using an information-theoretic algorithm. The main results are: (1) the population RGCs tend to fire in synchrony far more frequently than expected by chance during both NM and CB stimulation; (2) more synchronous groups could be formed and each group contains more neurons under NM than CB stimulation; (3) the individual neurons also participate in more groups and have more distinct partners in NM than CB stimulation. All these results suggest that the synchronized firings in RGCs are more extensive and diverse, which may account for more effective information processing in representing the natural visual environment. (cross-disciplinary physics and related areas of science and technology)

  12. Bone marrow mesenchymal stem cells protect against retinal ganglion cell loss in aged rats with glaucoma

    Directory of Open Access Journals (Sweden)

    Hu Y

    2013-10-01

    Full Text Available Ying Hu,1,2 Hai Bo Tan,1 Xin Mei Wang,3 Hua Rong,1 Hong Ping Cui,1 Hao Cui2 Departments of Ophthalmology, 1Shanghai East Hospital of Tongji University, Shanghai, 2First Affiliated Hospital, 3Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China Abstract: Glaucoma is a common eye disease in the aged population and has severe consequences. The present study examined the therapeutic effects of bone marrow mesenchymal stem cell (BMSC transplantation in preventing loss of visual function in aged rats with glaucoma caused by laser-induced ocular hypertension. We found that BMSCs promoted survival of retinal ganglion cells in the transplanted eye as compared with the control eye. Further, in swimming tests guided by visual cues, the rats with a BMSC transplant performed significantly better. We believe that BMSC transplantation therapy is effective in treating aged rats with glaucoma. Keywords: glaucoma, stem cell, transplantation, cell therapy, aging

  13. Rescuing axons from degeneration does not affect retinal ganglion cell death

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    S. de Lima

    2016-01-01

    Full Text Available After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD, an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18 treated with an exogenous calpain inhibitor (20 mM administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05 and an increase in the number of preserved fibers (P<0.05 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.

  14. Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.

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    Alena Z Minton

    Full Text Available Glaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1 is a 21-amino acid vasoactive peptide that plays a key role in the pathogenesis of glaucoma; however, the receptors mediating these effects have not been defined. In the current study, endothelin B (ET(B receptor expression was assessed in vivo, in the Morrison's ocular hypertension model of glaucoma in rats. Elevation of IOP in Brown Norway rats produced increased expression of ET(B receptors in the retina, mainly in retinal ganglion cells (RGCs, nerve fiber layer (NFL, and also in the inner plexiform layer (IPL and inner nuclear layer (INL. To determine the role of ET(B receptors in neurodegeneration, Wistar-Kyoto wild type (WT and ET(B receptor-deficient (KO rats were subjected to retrograde labeling with Fluoro-Gold (FG, following which IOP was elevated in one eye while the contralateral eye served as control. IOP elevation for 4 weeks in WT rats caused an appreciable loss of RGCs, which was significantly attenuated in KO rats. In addition, degenerative changes in the optic nerve were greatly reduced in KO rats compared to those in WT rats. Taken together, elevated intraocular pressure mediated increase in ET(B receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma. These findings raise the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glaucoma.

  15. Autophagy in retinal ganglion cells in a rhesus monkey chronic hypertensive glaucoma model.

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    Shuifeng Deng

    Full Text Available Primary open angle glaucoma (POAG is a neurodegenerative disease characterized by physiological intraocular hypertension that causes damage to the retinal ganglion cells (RGCs. In the past, RGC damage in POAG was suggested to have been attributed to RGC apoptosis. However, in the present study, we applied a model closer to human POAG through the use of a chronic hypertensive glaucoma model in rhesus monkeys to investigate whether another mode of progressive cell death, autophagy, was activated in the glaucomatous retinas. First, in the glaucomatous retinas, the levels of LC3B-II, LC3B-II/LC3B-I and Beclin 1 increased as demonstrated by Western blot analyses, whereas early or initial autophagic vacuoles (AVi and late or degraded autophagic vacuoles (AVd accumulated in the ganglion cell layer (GCL and in the inner plexiform layer (IPL as determined by transmission electron microscopy (TEM analysis. Second, lysosome activity and autophagosome-lysosomal fusion increased in the RGCs of the glaucomatous retinas, as demonstrated by Western blotting against lysosome associated membrane protein-1 (LAMP1 and double labeling against LC3B and LAMP1. Third, apoptosis was activated in the glaucomatous eyes with increased levels of caspase-3 and cleaved caspase-3 and an increased number of TUNEL-positive RGCs. Our results suggested that autophagy was activated in RGCs in the chronic hypertensive glaucoma model of rhesus monkeys and that autophagy may have potential as a new target for intervention in glaucoma treatment.

  16. Can Variability of Pattern ERG Signal Help to Detect Retinal Ganglion Cells Dysfunction in Glaucomatous Eyes?

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    Alberto Mavilio

    2015-01-01

    Full Text Available Objective. To evaluate variability of steady-state pattern electroretinogram (SS-PERG signal in normal, suspected, and glaucomatous eyes. Methods. Twenty-one subjects with suspected glaucoma due to disc abnormalities (GS, 37 patients with early glaucoma (EG, and 24 normal control (NC were tested with spectral-domain optical coherence tomography (SD-OCT, standard automated perimetry (SAP, and SS-PERG. Mean deviation (MD, pattern standard deviation (PSD, retinal nerve fiber layer (RNFL, and ganglionar complex cells (GCC were evaluated. The SS-PERG was recorded five consecutive times and the amplitude and phase of second harmonic were measured. PERG amplitude and coefficient of variation of phase (CVphase were recorded, and correlation with structural and functional parameters of disease, by means of one-way ANOVA and Pearson’s correlation, was analysed. Results. PERG amplitude was reduced, as expression of retinal ganglion cells (RGCs dysfunction, in EG patients and GS subjects compared to NC patients (P<0.0001. CVphase was significantly increased in EG patients and GS subjects, compared to healthy (P<0.0001, and it was also correlated with PSD (P=0.0009, GCC (P=0.028, and RNFL (P=0.0078 only in EG patients. Conclusions. Increased intrasession variability of phase in suspected glaucomatous eyes may be a sign of RGCs dysfunction.

  17. Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway.

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    Wan, Peixing; Su, Wenru; Zhang, Yingying; Li, Zhidong; Deng, Caibin; Zhuo, Yehong

    2017-09-15

    Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly attenuated retinal damage and RGC death in mice with acute glaucoma, with a significant decrease in reactive oxygen species (ROS) and inflammatory cytokine production in the retina. Furthermore, TMZ treatment directly decreased ROS production and rebalanced the intracellular redox state, thus contributing to the survival of RGCs in vitro TMZ treatment also reduced the production of inflammatory cytokines in vitro Mechanistically, the TMZ-mediated inhibition of apoptosis and inflammatory cytokine production in RGCs occurred via the regulation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1/caspase-8 pathway. Moreover, the TMZ-mediated neuroprotection in acute glaucoma was abrogated when an HO-1 inhibitor, SnPP, was used. Our findings identify potential mechanisms of RGC apoptosis and propose a novel therapeutic agent, TMZ, which exerts a precise neuroprotective effect against acute glaucoma. © 2017 The Author(s).

  18. Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma

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    Pitha, Ian F.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary Ellen; Oglesby, Ericka N.; Berlinicke, Cynthia A.; Mitchell, Katherine L.; Kim, Jessica; Jefferys, Joan J.

    2015-01-01

    Purpose To determine if oral losartan treatment decreases the retinal ganglion cell (RGC) death caused by experimental intraocular pressure (IOP) elevation in mice. Methods We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry. Results Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13), while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p glaucoma eyes (p = 0.007). Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP. Conclusions The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at the optic nerve head. PMID:26505191

  19. Elevated intracranial pressure causes optic nerve and retinal ganglion cell degeneration in mice.

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    Nusbaum, Derek M; Wu, Samuel M; Frankfort, Benjamin J

    2015-07-01

    The purpose of this study was to develop a novel experimental system for the modulation and measurement of intracranial pressure (ICP), and to use this system to assess the impact of elevated ICP on the optic nerve and retinal ganglion cells (RGCs) in CD1 mice. This system involved surgical implantation of an infusion cannula and a radiowave based pressure monitoring probe through the skull and into the subarachnoid space. The infusion cannula was used to increase ICP, which was measured by the probe and transmitted to a nearby receiver. The system provided robust and consistent ICP waveforms, was well tolerated, and was stable over time. ICP was elevated to approximately 30 mmHg for one week, after which we assessed changes in optic nerve structure with transmission electron microscopy in cross section and RGC numbers with antibody staining in retinal flat mounts. ICP elevation resulted in optic nerve axonal loss and disorganization, as well as RGC soma loss. We conclude that the controlled manipulation of ICP in active, awake mice is possible, despite their small size. Furthermore, ICP elevation results in visual system phenotypes of optic nerve and RGC degeneration, suggesting that this model can be used to study the impact of ICP on the visual system. Potentially, this model can also be used to study the relationship between ICP and IOP, as well diseases impacted by ICP variation such as glaucoma, idiopathic intracranial hypertension, and the spaceflight-related visual impairment intracranial pressure syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Neuroprotective effects of bis(7-tacrine against glutamate-induced retinal ganglion cells damage

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    Xu Zhi

    2010-03-01

    Full Text Available Abstract Background Glutamate-mediated excitotoxicity, primarily through N-methyl-D-aspartate (NMDA receptors, may be an important cause of retinal ganglion cells (RGCs death in glaucoma and several other retinal diseases. Bis(7-tacrine is a noncompetitive NMDA receptors antagonist that can prevent glutamate-induced hippocampal neurons damage. We tested the effects of bis(7-tacrine against glutamate-induced rat RGCs damage in vitro and in vivo. Results In cultured neonatal rats RGCs, the MTT assay showed that glutamate induced a concentration- and time-dependent toxicity. Bis(7-tacrine and memantine prevented glutamate-induced cell death in a concentration-dependent manner with IC50 values of 0.028 μM and 0.834 μM, respectively. The anti-apoptosis effects of bis(7-tacrine were confirmed by annexin V-FITC/PI staining. In vivo, TUNEL analysis and retrograde labeling analysis found that pretreatment with bis(7-tacrine(0.2 mg/kg induced a significant neuroprotective effect against glutamate-induced RGCs damage. Conclusions Our results showed that bis(7-tacrine had neuroprotective effects against glutamate-induced RGCs damage in vitro and in vivo, possibly through the drug's anti-NMDA receptor effects. These findings make bis(7-tacrine potentially useful for treating a variety of ischemic or traumatic retinopathies inclusive of glaucoma.

  1. Optimal voltage stimulation parameters for network-mediated responses in wild type and rd10 mouse retinal ganglion cells

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    Jalligampala, Archana; Sekhar, Sudarshan; Zrenner, Eberhart; Rathbun, Daniel L.

    2017-04-01

    To further improve the quality of visual percepts elicited by microelectronic retinal prosthetics, substantial efforts have been made to understand how retinal neurons respond to electrical stimulation. It is generally assumed that a sufficiently strong stimulus will recruit most retinal neurons. However, recent evidence has shown that the responses of some retinal neurons decrease with excessively strong stimuli (a non-monotonic response function). Therefore, it is necessary to identify stimuli that can be used to activate the majority of retinal neurons even when such non-monotonic cells are part of the neuronal population. Taking these non-monotonic responses into consideration, we establish the optimal voltage stimulation parameters (amplitude, duration, and polarity) for epiretinal stimulation of network-mediated (indirect) ganglion cell responses. We recorded responses from 3958 mouse retinal ganglion cells (RGCs) in both healthy (wild type, WT) and a degenerating (rd10) mouse model of retinitis pigmentosa—using flat-mounted retina on a microelectrode array. Rectangular monophasic voltage-controlled pulses were presented with varying voltage, duration, and polarity. We found that in 4-5 weeks old rd10 mice the RGC thresholds were comparable to those of WT. There was a marked response variability among mouse RGCs. To account for this variability, we interpolated the percentage of RGCs activated at each point in the voltage-polarity-duration stimulus space, thus identifying the optimal voltage-controlled pulse (-2.4 V, 0.88 ms). The identified optimal voltage pulse can activate at least 65% of potentially responsive RGCs in both mouse strains. Furthermore, this pulse is well within the range of stimuli demonstrated to be safe and effective for retinal implant patients. Such optimized stimuli and the underlying method used to identify them support a high yield of responsive RGCs and will serve as an effective guideline for future in vitro investigations of

  2. Diversity of retinal ganglion cells identified by transient GFP transfection in organotypic tissue culture of adult marmoset monkey retina.

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    Satoru Moritoh

    Full Text Available The mammalian retina has more diversity of neurons than scientists had once believed in order to establish complicated vision processing. In the monkey retina, morphological diversity of retinal ganglion cells (RGCs besides dominant midget and parasol cells has been suggested. However, characteristic subtypes of RGCs in other species such as bistratified direction-selective ganglion cells (DSGC have not yet been identified. Increasing interest has been shown in the common marmoset (Callithrix jacchus monkey as a "super-model" of neuroscientific research. Here, we established organotypic tissue culture of the adult marmoset monkey retina with particle-mediated gene transfer of GFP to survey the morphological diversity of RGCs. We successfully incubated adult marmoset monkey retinas for 2 to 4 days ex vivo for transient expression of GFP. We morphologically examined 121 RGCs out of more than 3240 GFP-transfected cells in 5 retinas. Among them, we identified monostratified or broadly stratified ganglion cells (midget, parasol, sparse, recursive, thorny, and broad thorny ganglion cells, and bistratified ganglion cells (recursive, large, and small bistratified ganglion cells [blue-ON/yellow-OFF-like]. By this survey, we also found a candidate for bistratified DSGC whose dendrites were well cofasciculated with ChAT-positive starburst dendrites, costratified with ON and OFF ChAT bands, and had honeycomb-shaped dendritic arbors morphologically similar to those in rabbits. Our genetic engineering method provides a new approach to future investigation for morphological and functional diversity of RGCs in the monkey retina.

  3. A dedicated circuit links direction-selective retinal ganglion cells to the primary visual cortex

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    Cruz-Martín, Alberto; El-Danaf, Rana N.; Osakada, Fumitaka; Sriram, Balaji; Dhande, Onkar S.; Nguyen, Phong L.; Callaway, Edward M.; Ghosh, Anirvan; Huberman, Andrew D.

    2014-03-01

    How specific features in the environment are represented within the brain is an important unanswered question in neuroscience. A subset of retinal neurons, called direction-selective ganglion cells (DSGCs), are specialized for detecting motion along specific axes of the visual field. Despite extensive study of the retinal circuitry that endows DSGCs with their unique tuning properties, their downstream circuitry in the brain and thus their contribution to visual processing has remained unclear. In mice, several different types of DSGCs connect to the dorsal lateral geniculate nucleus (dLGN), the visual thalamic structure that harbours cortical relay neurons. Whether direction-selective information computed at the level of the retina is routed to cortical circuits and integrated with other visual channels, however, is unknown. Here we show that there is a di-synaptic circuit linking DSGCs with the superficial layers of the primary visual cortex (V1) by using viral trans-synaptic circuit mapping and functional imaging of visually driven calcium signals in thalamocortical axons. This circuit pools information from several types of DSGCs, converges in a specialized subdivision of the dLGN, and delivers direction-tuned and orientation-tuned signals to superficial V1. Notably, this circuit is anatomically segregated from the retino-geniculo-cortical pathway carrying non-direction-tuned visual information to deeper layers of V1, such as layer 4. Thus, the mouse harbours several functionally specialized, parallel retino-geniculo-cortical pathways, one of which originates with retinal DSGCs and delivers direction- and orientation-tuned information specifically to the superficial layers of the primary visual cortex. These data provide evidence that direction and orientation selectivity of some V1 neurons may be influenced by the activation of DSGCs.

  4. Differential responses to high-frequency electrical stimulation in ON and OFF retinal ganglion cells

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    Twyford, Perry; Cai, Changsi; Fried, Shelley

    2014-04-01

    Objective. The field of retinal prosthetics for artificial vision has advanced considerably in recent years, however clinical outcomes remain inconsistent. The performance of retinal prostheses is likely limited by the inability of electrical stimuli to preferentially activate different types of retinal ganglion cell (RGC). Approach. Here we examine the response of rabbit RGCs to high-frequency stimulation, using biphasic pulses applied at 2000 pulses per second. Responses were recorded using cell-attached patch clamp methods, and stimulation was applied epiretinally via a small cone electrode. Main results. When prolonged stimulus trains were applied to OFF-brisk transient (BT) RGCs, the cells exhibited a non-monotonic relationship between response strength and stimulus amplitude; this response pattern was different from those elicited previously by other electrical stimuli. When the amplitude of the stimulus was modulated transiently from a non-zero baseline amplitude, ON-BT and OFF-BT cells exhibited different activity patterns: ON cells showed an increase in activity while OFF cells exhibited a decrease in activity. Using a different envelope to modulate the amplitude of the stimulus, we observed the opposite effect: ON cells exhibited a decrease in activity while OFF cells show an increase in activity. Significance. As ON and OFF RGCs often exhibit opposing activity patterns in response to light stimulation, this work suggests that high-frequency electrical stimulation of RGCs may be able to elicit responses that are more physiological than traditional pulsatile stimuli. Additionally, the prospect of an electrical stimulus capable of cell-type specific selective activation has broad applications throughout the fields of neural stimulation and neuroprostheses.

  5. Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury.

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    Lin Cheng

    Full Text Available Epigenetic predisposition is thought to critically contribute to adult-onset disorders, such as retinal neurodegeneration. The histone methyltransferase, enhancer of zeste homolog 2 (Ezh2, is transiently expressed in the perinatal retina, particularly enriched in retinal ganglion cells (RGCs. We previously showed that embryonic deletion of Ezh2 from retinal progenitors led to progressive photoreceptor degeneration throughout life, demonstrating a role for embryonic predisposition of Ezh2-mediated repressive mark in maintaining the survival and function of photoreceptors in the adult. Enrichment of Ezh2 in RGCs leads to the question if Ezh2 also mediates gene expression and function in postnatal RGCs, and if its deficiency changes RGC susceptibility to cell death under injury or disease in the adult. To test this, we generated mice carrying targeted deletion of Ezh2 from RGC progenitors driven by Math5-Cre (mKO. mKO mice showed no detectable defect in RGC development, survival, or cell homeostasis as determined by physiological analysis, live imaging, histology, and immunohistochemistry. Moreover, RGCs of Ezh2 deficient mice revealed similar susceptibility against glaucomatous and acute optic nerve trauma-induced neurodegeneration compared to littermate floxed or wild-type control mice. In agreement with the above findings, analysis of RNA sequencing of RGCs purified from Ezh2 deficient mice revealed few gene changes that were related to RGC development, survival and function. These results, together with our previous report, support a cell lineage-specific mechanism of Ezh2-mediated gene repression, especially those critically involved in cellular function and homeostasis.

  6. Isolation and Molecular Profiling of Primary Mouse Retinal Ganglion Cells: Comparison of Phenotypes from Healthy and Glaucomatous Retinas

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    Chintalapudi, Sumana R.; Djenderedjian, Levon; Stiemke, Andrew B.; Steinle, Jena J.; Jablonski, Monica M.; Morales-Tirado, Vanessa M.

    2016-01-01

    Loss of functional retinal ganglion cells (RGC) is an element of retinal degeneration that is poorly understood. This is in part due to the lack of a reliable and validated protocol for the isolation of primary RGCs. Here we optimize a feasible, reproducible, standardized flow cytometry-based protocol for the isolation and enrichment of homogeneous RGC with the Thy1.2hiCD48negCD15negCD57neg surface phenotype. A three-step validation process was performed by: (1) genomic profiling of 25-genes ...

  7. Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type

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    Im, Maesoon; Fried, Shelley I.

    2016-04-01

    Objective. To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates. Approach. We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10-1000 ms). Each stimulus was a 4 ms long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode. Main results. ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported ‘reset’ behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4-7 Hz) that maximized the ratio of the responses arising in ON versus OFF cells. Significance. Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5-7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (> ˜7 Hz) due to the reset while responses of OFF cells are strong at low rates (cells more closely match physiological patterns (Im and Fried 2015

  8. Can Retinal Ganglion Cell Dipoles Seed Iso-Orientation Domains in the Visual Cortex?

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    Schottdorf, Manuel; Eglen, Stephen J.; Wolf, Fred; Keil, Wolfgang

    2014-01-01

    It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglion cells (RGCs). The typical spacing between adjacent cortical orientation columns preferring the same orientation then arises via Moiré-Interference between hexagonal ON/OFF RGC mosaics. While this Moiré-Interference critically depends on long-range hexagonal order within the RGC mosaics, a recent statistical analysis of RGC receptive field positions found no evidence for such long-range positional order. Hexagonal order may be only one of several ways to obtain spatially repetitive OPMs in the statistical connectivity model. Here, we investigate a more general requirement on the spatial structure of RGC mosaics that can seed the emergence of spatially repetitive cortical OPMs, namely that angular correlations between so-called RGC dipoles exhibit a spatial structure similar to that of OPM autocorrelation functions. Both in cat beta cell mosaics as well as primate parasol receptive field mosaics we find that RGC dipole angles are spatially uncorrelated. To help assess the level of these correlations, we introduce a novel point process that generates mosaics with realistic nearest neighbor statistics and a tunable degree of spatial correlations of dipole angles. Using this process, we show that given the size of available data sets, the presence of even weak angular correlations in the data is very unlikely. We conclude that the layout of ON/OFF ganglion cell mosaics lacks the spatial structure necessary to seed iso-orientation domains in the primary visual cortex. PMID:24475081

  9. Coding properties of three intrinsically distinct retinal ganglion cells under periodic stimuli: a computational study

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    Lei Wang

    2016-09-01

    Full Text Available As the sole output neurons in the retina, ganglion cells play significant roles in transforming visual information into spike trains, and then transmitting them to the higher visual centers. However, coding strategies that retinal ganglion cells (RGCs adopt to accomplish these processes are not completely clear yet. To clarify these issues, we investigate the coding properties of three types of RGCs (repetitive spiking, tonic firing, and phasic firing by two different measures (spike-rate and spike-latency. Model results show that for periodic stimuli, repetitive spiking RGC and tonic RGC exhibit similar spike-rate patterns. Their spike-rates decrease gradually with increased stimulus frequency, moreover, variation of stimulus amplitude would change the two RGCs’ spike-rate patterns. For phasic RGC, it activates strongly at medium levels of frequency when the stimulus amplitude is low. While if high stimulus amplitude is applied, phasic RGC switches to respond strongly at low frequencies. These results suggest that stimulus amplitude is a prominent factor in regulating RGCs in encoding periodic signals. Similar conclusions can be drawn when analyzes spike-latency patterns of the three RGCs. More importantly, the above phenomena can be accurately reproduced by Hodgkin’s three classes of neurons, indicating that RGCs can perform the typical three classes of firing dynamics, depending on the distinctions of ion channel densities. Consequently, model results from the three RGCs may be not specific, but can also applicable to neurons in other brain regions which exhibit part(s or all of the Hodgkin’s three excitabilities.

  10. Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

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    L.D. Loopuijt

    2007-10-01

    Full Text Available To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37 on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 µm ("thin" or "thick" dendrites, respectively. Three cells (4.5% were bistratified, having thick dendrites, and the others (95.5% were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40% and 2 groups with inner (50-100% stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

  11. Retinal Astrocytes and GABAergic Wide-Field Amacrine Cells Express PDGFRα: Connection to Retinal Ganglion Cell Neuroprotection by PDGF-AA.

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    Takahama, Shokichi; Adetunji, Modupe O; Zhao, Tantai; Chen, Shan; Li, Wei; Tomarev, Stanislav I

    2017-09-01

    Our previous experiments demonstrated that intravitreal injection of platelet-derived growth factor-AA (PDGF-AA) provides retinal ganglion cell (RGC) neuroprotection in a rodent model of glaucoma. Here we used PDGFRα-enhanced green fluorescent protein (EGFP) mice to identify retinal cells that may be essential for RGC protection by PDGF-AA. PDGFRα-EGFP mice expressing nuclear-targeted EGFP under the control of the PDGFRα promoter were used. Localization of PDGFRα in the neural retina was investigated by confocal imaging of EGFP fluorescence and immunofluorescent labeling with a panel of antibodies recognizing different retinal cell types. Primary cultures of mouse RGCs were produced by immunopanning. Neurobiotin injection of amacrine cells in a flat-mounted retina was used for the identification of EGFP-positive amacrine cells in the inner nuclear layer. In the mouse neural retina, PDGFRα was preferentially localized in the ganglion cell and inner nuclear layers. Immunostaining of the retina demonstrated that astrocytes in the ganglion cell layer and a subpopulation of amacrine cells in the inner nuclear layer express PDGFRα, whereas RGCs (in vivo or in vitro) did not. PDGFRα-positive amacrine cells are likely to be Type 45 gamma-aminobutyric acidergic (GABAergic) wide-field amacrine cells. These data indicate that the neuroprotective effect of PDGF-AA in a rodent model of glaucoma could be mediated by astrocytes and/or a subpopulation of amacrine cells. We suggest that after intravitreal injection of PDGF-AA, these cells secrete factors protecting RGCs.

  12. Inner nuclear layer thickening is inversley proportional to retinal ganglion cell loss in optic neuritis.

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    Megha Kaushik

    Full Text Available AIM: To examine the relationship between retinal ganglion cell loss and changes in the inner nuclear layer (INL in optic neuritis (ON. METHODS: 36 multiple sclerosis (MS patients with a history of ON and 36 age and sex-matched controls underwent Optical Coherence Tomography. The paramacular retinal nerve fiber layer (RNFL, combined ganglion cell and inner plexiform layers (GCL/IPL and inner nuclear layer (INL thickness were measured at 36 points around the fovea. To remove inter-subject variability, the difference in thickness of each layer between the ON and fellow eye of each patient was calculated. A topographic analysis was conducted. RESULTS: The INL of the ON patients was thicker than the controls (42.9µm versus 39.6µm, p=0.002. ON patients also had a thinner RNFL (27.8µm versus 32.2µm, p<0.001 and GCL/IPL (69.3µm versus 98.1µm, p<0.001. Among the controls, there was no correlation between RNFL and GCL/IPL as well as RNFL and INL, but a positive correlation was seen between GCL/IPL and INL (r=0.65, p<0.001. In the ON group, there was a positive correlation between RNFL and GCL/IPL (r=0.80, p<0.001 but a negative correlation between RNFL and INL (r=-0.61, p<0.001 as well as GCL/IPL and INL (r=-0.44, p=0.007. The negative correlation between GCL/IPL and INL strengthened in the ON group when inter-subject variability was removed (r=-0.75, p<0.001. Microcysts within the INL were present in 5 ON patients, mainly in the superior and infero-nasal paramacular regions. While patients with microcysts lay at the far end of the correlation curve between GCL/IPL and INL (i.e. larger INL and smaller GCL/IPL compared to other patients, their exclusion did not affect the correlation (r= -0.76, p<0.001. CONCLUSIONS: INL enlargement in MS-related ON is associated with the severity of GCL loss. This is a continuous relationship and patients with INL microcysts may represent the extreme end of the scale.

  13. Valproic acid prevents NMDA-induced retinal ganglion cell death via stimulation of neuronal TrkB receptor signaling.

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    Kimura, Atsuko; Namekata, Kazuhiko; Guo, Xiaoli; Noro, Takahiko; Harada, Chikako; Harada, Takayuki

    2015-03-01

    Valproic acid (VPA) is widely prescribed for treatment of epilepsy, mood disorders, migraines, and neuropathic pain. It exerts its therapeutic benefits through multiple mechanisms, including enhancement of GABAergic activity, activation of prosurvival protein kinases, and inhibition of histone deacetylase. Increasing evidence suggests that VPA possesses neuroprotective properties. We examined neuroprotective effects of VPA in an N-methyl-d-aspartate (NMDA) excitotoxicity model, which mimics some of the pathological features of glaucoma. In vivo retinal imaging using optical coherence tomography revealed that NMDA-induced retinal degeneration was suppressed in the VPA-treated retina, and histological analyses confirmed that VPA reduced retinal ganglion cell death. In vivo electrophysiological analyses demonstrated that visual impairment was prevented in the VPA-treated retina, clearly establishing both histological and functional effects of VPA. Brain-derived neurotrophic factor (BDNF) expression was up-regulated in Müller glial cells, and neuroprotective effects of VPA on retinal ganglion cells were significantly reduced in a conditional knockout mouse strain with deletion of tropomyosin receptor kinase B (TrkB), a receptor for BDNF from retinal ganglion cells. The results show that VPA stimulates BDNF up-regulation in Müller glial cells and provides direct evidence that neuronal TrkB is important in VPA-mediated neuroprotection. Also, VPA suppresses oxidative stress induced by NMDA in the retina. Our findings raise intriguing possibilities that the widely prescribed drug VPA may be useful for treatment of glaucoma. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma.

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    Harry A Quigley

    Full Text Available To determine if oral losartan treatment decreases the retinal ganglion cell (RGC death caused by experimental intraocular pressure (IOP elevation in mice.We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry.Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13, while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p < 0.0001. The lower RGC loss with losartan was significantly less than the loss with spironolactone or enalapril (regression model p = 0.001; drug treatment group term p = 0.01. Both losartan and enalapril significantly lowered blood pressure (p< 0.001, but losartan was protective, while enalapril led to worse than water-treated RGC loss. RGC loss after crush injury was unaffected by losartan treatment (difference from control p = 0.9. Survival of RGC in cell culture was not prolonged by sartan treatment. Axonal transport blockade after 3 day IOP elevations was less in losartan-treated than in control glaucoma eyes (p = 0.007. Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP.The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at

  15. The role of intrinsically photosensitive retinal ganglion cells in nonimage-forming responses to light

    Directory of Open Access Journals (Sweden)

    Warthen DM

    2012-09-01

    Full Text Available Daniel M Warthen,1,2 Ignacio Provencio11Department of Biology, University of Virginia, Charlottesville, VA, USA; 2Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USAAbstract: Light exerts many effects on behavior and physiology. These effects can be characterized as either image-forming or nonimage-forming (NIF visual processes. Image-forming vision refers to the process of detecting objects and organisms in the environment and distinguishing their physical characteristics, such as size, shape, and direction of motion. NIF vision, in contrast, refers to effects of light that are independent of fine spatiotemporal vision. NIF effects are many and varied, ranging from modulation of basal physiology, such as heart rate and body temperature, to changes in higher functions, such as mood and cognitive performance. In mammals, many NIF effects of light are dependent upon the inner retinal photopigment melanopsin and the cells in which melanopsin is expressed, the intrinsically photosensitive retinal ganglion cells (ipRGCs. The ipRGCs project broadly throughout the brain. Many of these projections terminate in areas known to mediate NIF effects, while others terminate in regions whose link to photoreception remains to be established. Additionally, the presence of ipRGC projections to areas of the brain with no known link to photoreception suggests the existence of additional ipRGC-mediated NIF effects. This review summarizes the known NIF effects of light and the role of melanopsin and ipRGCs in driving these effects, with an eye toward stimulating further investigation of the many and varied effects of light on physiology and behavior.Keywords: amygdala, bed nucleus of the stria terminalis, melanopsin, opsin, optic nerve, retina

  16. Comparative study of photoreceptor and retinal ganglion cell topography and spatial resolving power in Dipsadidae snakes.

    Science.gov (United States)

    Hauzman, Einat; Bonci, Daniela M O; Grotzner, Sonia R; Mela, Maritana; Liber, André M P; Martins, Sonia L; Ventura, Dora F

    2014-01-01

    The diurnal Dipsadidae snakes Philodryas olfersii and P. patagoniensis are closely related in their phylogeny but inhabit different ecological niches. P. olfersii is arboreal, whereas P. patagoniensis is preferentially terrestrial. The goal of the present study was to compare the density and topography of neurons, photoreceptors, and cells in the ganglion cell layer in the retinas of these two species using immunohistochemistry and Nissl staining procedures and estimate the spatial resolving power of their eyes based on the ganglion cell peak density. Four morphologically distinct types of cones were observed by scanning electron microscopy, 3 of which were labeled with anti-opsin antibodies: large single cones and double cones labeled by the antibody JH492 and small single cones labeled by the antibody JH455. The average densities of photoreceptors and neurons in the ganglion cell layer were similar in both species (∼10,000 and 7,000 cells·mm(-2), respectively). The estimated spatial resolving power was also similar, ranging from 2.4 to 2.7 cycles·degree(-1). However, the distribution of neurons had different specializations. In the arboreal P. olfersii, the isodensity maps had a horizontal visual streak, with a peak density in the central region and a lower density in the dorsal retina. This organization might be relevant for locomotion and hunting behavior in the arboreal layer. In the terrestrial P. patagoniensis, a concentric pattern of decreasing cell density emanated from an area centralis located in the naso-ventral retina. Lower densities were observed in the dorsal region. The ventrally high density improves the resolution in the superior visual field and may be an important adaptation for terrestrial snakes to perceive the approach of predators from above. © 2014 S. Karger AG, Basel.

  17. APP upregulation contributes to retinal ganglion cell degeneration via JNK3.

    Science.gov (United States)

    Liu, Chao; Zhang, Cheng-Wu; Zhou, Yi; Wong, Wan Qing; Lee, Liying Corinne; Ong, Wei Yi; Yoon, Sung Ok; Hong, Wanjin; Fu, Xin-Yuan; Soong, Tuck Wah; Koo, Edward H; Stanton, Lawrence W; Lim, Kah-Leong; Xiao, Zhi-Cheng; Dawe, Gavin S

    2018-03-01

    Axonal injury is a common feature of central nervous system insults. Upregulation of amyloid precursor protein (APP) is observed following central nervous system neurotrauma and is regarded as a marker of central nervous system axonal injury. However, the underlying mechanism by which APP mediates neuronal death remains to be elucidated. Here, we used mouse optic nerve axotomy (ONA) to model central nervous system axonal injury replicating aspects of retinal ganglion cell (RGC) death in optic neuropathies. APP and APP intracellular domain (AICD) were upregulated in retina after ONA and APP knockout reduced Tuj1 + RGC loss. Pathway analysis of microarray data combined with chromatin immunoprecipitation and a luciferase reporter assay demonstrated that AICD interacts with the JNK3 gene locus and regulates JNK3 expression. Moreover, JNK3 was found to be upregulated after ONA and to contribute to Tuj1 + RGC death. APP knockout reduced the ONA-induced enhanced expression of JNK3 and phosphorylated JNK (pJNK). Gamma-secretase inhibitors prevented production of AICD, reduced JNK3 and pJNK expression similarly, and protected Tuj1 + RGCs from ONA-induced cell death. Together these data indicate that ONA induces APP expression and that gamma-secretase cleavage of APP releases AICD, which upregulates JNK3 leading to RGC death. This pathway may be a novel target for neuronal protection in optic neuropathies and other forms of neurotrauma.

  18. Rasagiline-induced delay of retinal ganglion cell death in experimental glaucoma in rats.

    Science.gov (United States)

    Levkovitch-Verbin, Hani; Vander, Shelly; Melamed, Shlomo

    2011-01-01

    To evaluate the neuroprotective effect of rasagiline (N-propargyl-1 (R)-aminoindan), a selective monoamine oxidase inhibitor, on the survival of retinal ganglion cells (RGCs) in glaucomatous rat eyes. Rasagiline is an FDA approved anti-Parkinson disease drug with neuroprotective capabilities that were shown in many models of brain damage. The neuroprotective effect of daily intraperitoneal (IP) injections of rasagiline (0.5 mg/kg and 3 mg/kg) was evaluated and compared with saline injections using the translimbal photocoagulation model of experimental glaucoma in Wistar rats. Intraocular pressure (IOP) was measured before and immediately after the laser treatment, and then weekly. Seven weeks after the induction of glaucoma, the animals were killed, the eyes were enucleated and the retinas were prepared as whole mounts. Fluoro-gold had been injected into the superior colliculus 10 days before enucleation, and RGC survival was evaluated by counting the surviving labeled RGCs in a masked way. All rats (n=29) displayed significant IOP elevation and RGC damage. Seven weeks after the induction of glaucoma, the mean RGC survival was 43±8% in the rasagiline 3 mg/kg-treated group and 43±9% in the rasagiline 0.5 mg/kg-treated group compared with 23%±4% in the saline-treated (control) group (P=0.01 and P=0.02, respectively). Systemic treatment with rasagiline significantly enhances the survival of RGCs in experimental glaucoma.

  19. Isolation of Primary Murine Retinal Ganglion Cells (RGCs) by Flow Cytometry.

    Science.gov (United States)

    Chintalapudi, Sumana R; Patel, Need N; Goldsmith, Zachary K; Djenderedjian, Levon; Wang, Xiang Di; Marion, Tony N; Jablonski, Monica M; Morales-Tirado, Vanessa M

    2017-07-05

    Neurodegenerative diseases often have a devastating impact on those affected. Retinal ganglion cell (RGC) loss is implicated in an array of diseases, including diabetic retinopathy and glaucoma, in addition to normal aging. Despite their importance, RGCs have been extremely difficult to study until now due in part to the fact that they comprise only a small percentage of the wide variety of cells in the retina. In addition, current isolation methods use intracellular markers to identify RGCs, which produce non-viable cells. These techniques also involve lengthy isolation protocols, so there is a lack of practical, standardized, and dependable methods to obtain and isolate RGCs. This work describes an efficient, comprehensive, and reliable method to isolate primary RGCs from mice retinae using a protocol based on both positive and negative selection criteria. The presented methods allow for the future study of RGCs, with the goal of better understanding the major decline in visual acuity that results from the loss of functional RGCs in neurodegenerative diseases.

  20. Electrical activity of ON and OFF retinal ganglion cells: a modelling study

    Science.gov (United States)

    Guo, Tianruo; Tsai, David; Morley, John W.; Suaning, Gregg J.; Kameneva, Tatiana; Lovell, Nigel H.; Dokos, Socrates

    2016-04-01

    Objective. Retinal ganglion cells (RGCs) demonstrate a large range of variation in their ionic channel properties and morphologies. Cell-specific properties are responsible for the unique way RGCs process synaptic inputs, as well as artificial electrical signals such as that from a visual prosthesis. A cell-specific computational modelling approach allows us to examine the functional significance of regional membrane channel expression and cell morphology. Approach. In this study, an existing RGC ionic model was extended by including a hyperpolarization activated non-selective cationic current as well as a T-type calcium current identified in recent experimental findings. Biophysically-defined model parameters were simultaneously optimized against multiple experimental recordings from ON and OFF RGCs. Main results. With well-defined cell-specific model parameters and the incorporation of detailed cell morphologies, these models were able to closely reconstruct and predict ON and OFF RGC response properties recorded experimentally. Significance. The resulting models were used to study the contribution of different ion channel properties and spatial structure of neurons to RGC activation. The techniques of this study are generally applicable to other excitable cell models, increasing the utility of theoretical models in accurately predicting the response of real biological neurons.

  1. Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

    Science.gov (United States)

    Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

    2017-02-01

    In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. A Pixel-Encoder Retinal Ganglion Cell with Spatially Offset Excitatory and Inhibitory Receptive Fields

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    Keith P. Johnson

    2018-02-01

    Full Text Available The spike trains of retinal ganglion cells (RGCs are the only source of visual information to the brain. Here, we genetically identify an RGC type in mice that functions as a pixel encoder and increases firing to light increments (PixON-RGC. PixON-RGCs have medium-sized dendritic arbors and non-canonical center-surround receptive fields. From their receptive field center, PixON-RGCs receive only excitatory input, which encodes contrast and spatial information linearly. From their receptive field surround, PixON-RGCs receive only inhibitory input, which is temporally matched to the excitatory center input. As a result, the firing rate of PixON-RGCs linearly encodes local image contrast. Spatially offset (i.e., truly lateral inhibition of PixON-RGCs arises from spiking GABAergic amacrine cells. The receptive field organization of PixON-RGCs is independent of stimulus wavelength (i.e., achromatic. PixON-RGCs project predominantly to the dorsal lateral geniculate nucleus (dLGN of the thalamus and likely contribute to visual perception.

  3. Effects of L-carnitine on high glucose-induced oxidative stress in retinal ganglion cells.

    Science.gov (United States)

    Cao, Yu; Li, Xin; Shi, Ping; Wang, Le-xin; Sui, Zhong-guo

    2014-01-01

    Oxidative stress plays a role in diabetic retinopathy. L-Carnitine is an endogenous mitochondrial membrane compound. To elucidate the protective effects of L-carnitine on high glucose-induced oxidative stress in retinal ganglion cells (RGCs). Hoechst 33258 staining was used to estimate cell loss. Mitochondrial function was predicted by mitochondrial membrane potential (ΔΨm) measurement. The expression of apoptosis-related protein was measured by Western blotting. Assays for reactive oxygen species (ROS) accumulation, lipid peroxidation, total antioxidative capacity (T-AOC) and antioxidant defense enzymes were completed to explain the antioxidative capacity of L-carnitine. L-Carnitine (12 h) inhibited high glucose-mediated cell loss and restored mitochondrial function including a reversion of ΔΨm loss and cytochrome c release. Cell apoptosis triggered by high glucose was also inhibited by L-carnitine, characterized by the downregulation of caspase-9, caspase-3 and Bax/Bcl-2. Furthermore, L-carnitine inhibited high glucose-induced ROS production and lipid peroxidation and promoted endogenous antioxidant defense components including superoxide dismutase, glutathione peroxidase, catalase and T-AOC in a concentration-dependent manner. L-Carnitine may protect RGCs from high glucose-induced injury through the inhibition of oxidative damage, mitochondrial dysfunction and, ultimately, cell apoptosis. © 2014 S. Karger AG, Basel.

  4. Loss of Melanopsin-Expressing Retinal Ganglion Cells in Severely Staged Glaucoma Patients

    DEFF Research Database (Denmark)

    Obara, Elisabeth Anne; Hannibal, Jens; Heegaard, Steffen

    2016-01-01

    Purpose: Multiple studies have shown overwhelming evidence supporting the impairment of melanopsin function due to glaucoma. However, few studies have been carried out in humans analyzing the histology of melanopsin-expressing retinal ganglion cells (mRGCs) in retinas with glaucoma. The aim...... of this study was to analyze the pattern of expression of mRGCs relative to RGCs in the normal retina and retinas harboring varying stages of glaucoma. Methods: Paraffin-embedded human donor eyes with glaucoma (n = 11) and age-matched controls (n = 10) were obtained from Department of Pathology at Rigshospital...... difference was observed in mRGC expression in the normal retinas and mild-staged retinas with glaucoma; the densities of mRGCs were 3.08 ± 0.47 and 3.00 ± 0.13 cell counts/mm2, respectively. However, the severely staged retinas with glaucoma showed a significant loss in mRGCs density, 1.09 ± 0.35 cell counts...

  5. Imipramine protects retinal ganglion cells from oxidative stress through the tyrosine kinase receptor B signaling pathway

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    Ming-lei Han

    2016-01-01

    Full Text Available Retinal ganglion cell (RGC degeneration is irreversible in glaucoma and tyrosine kinase receptor B (TrkB-associated signaling pathways have been implicated in the process. In this study, we attempted to examine whether imipramine, a tricyclic antidepressant, may protect hydrogen peroxide (H 2 O 2 -induced RGC degeneration through the activation of the TrkB pathway in RGC-5 cell lines. RGC-5 cell lines were pre-treated with imipramine 30 minutes before exposure to H 2 O 2 . Western blot assay showed that in H 2 O 2 -damaged RGC-5 cells, imipramine activated TrkB pathways through extracellular signal-regulated protein kinase/TrkB phosphorylation. TUNEL staining assay also demonstrated that imipramine ameliorated H 2 O 2 -induced apoptosis in RGC-5 cells. Finally, TrkB-IgG intervention was able to reverse the protective effect of imipramine on H 2 O 2 -induced RGC-5 apoptosis. Imipramine therefore protects RGCs from oxidative stress-induced apoptosis through the TrkB signaling pathway.

  6. Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others.

    Science.gov (United States)

    Norsworthy, Michael W; Bei, Fengfeng; Kawaguchi, Riki; Wang, Qing; Tran, Nicholas M; Li, Yi; Brommer, Benedikt; Zhang, Yiming; Wang, Chen; Sanes, Joshua R; Coppola, Giovanni; He, Zhigang

    2017-06-21

    At least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration. Transcriptome profiling indicated that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, α-RGCs, which preferentially regenerate following treatments such as Pten deletion, were killed by Sox11 overexpression. Thus, Sox11 promotes regeneration of non-α-RGCs, which are refractory to Pten deletion-induced regeneration. We conclude that Sox11 can reprogram adult RGCs to a growth-competent state, suggesting that different growth-promoting interventions promote regeneration in distinct neuronal types. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Segregation of ipsilateral retinal ganglion cell axons at the optic chiasm requires the Shh receptor Boc.

    Science.gov (United States)

    Fabre, Pierre J; Shimogori, Tomomi; Charron, Frédéric

    2010-01-06

    The pattern of contralaterally and ipsilaterally projecting retinal ganglion cell (RGC) axons at the optic chiasm is essential for the establishment of binocular vision. Contralateral axons cross the chiasm midline as they progress from the optic nerve to the optic tract. In contrast, ipsilateral axons deviate from the chiasm and continue in the ipsilateral optic tract, avoiding the chiasm midline. The molecular mechanism underlying this phenomenon is not completely understood. Here we show that the Sonic Hedgehog (Shh) receptor Boc is enriched in ipsilateral RGCs of the developing retina. Together with the presence of Shh at the midline, this complementary expression pattern led us to hypothesize that Shh might repel ipsilateral RGC axons at the chiasm. Consistent with this hypothesis, we found that only Boc-positive RGC axons retract in vitro in response to Shh and that this response is lost in Boc mutant RGCs. In vivo, we show that Boc is required for the normal segregation of ipsilateral axons at the optic chiasm and, conversely, that Boc expression in contralateral RGCs prevents their axons from crossing the optic chiasm. Together, these results suggest that Shh repels ipsilateral RGC axons at the optic chiasm via its receptor Boc. This work identifies a novel molecular pathway required for the segregation of axons at the optic chiasm.

  8. Ganglion cell-inner plexiform layer and retinal nerve fibre layer changes within the macula in retinitis pigmentosa: a spectral domain optical coherence tomography study.

    Science.gov (United States)

    Yoon, Chang Ki; Yu, Hyeong Gon

    2018-03-01

    To investigate how macular ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thicknesses within the macula change with retinitis pigmentosa (RP) severity. Spectral domain optical coherence tomography (SD-OCT) was used to examine 177 patients with RP and 177 normal controls. An optical coherence tomography (OCT) line scan was used to grade RP severity. Retinitis pigmentosa (RP) was categorized as more advanced if there was no identifiable inner segment ellipsoid (ISe) band (NISE) and as less advanced if an ISe band could be identified and peripheral loss of ISe was apparent (IISE). Ganglion cell-inner plexiform layer (GCIPL) and RNFL thicknesses were manually measured on OCT images and analysed. Pearson's correlation analyses were used to examine correlations between GCIPL thickness, RNFL thickness, visual acuity (VA) and visual field extent in patients and controls. Ganglion cell-inner plexiform layer (GCIPL) was significantly thicker in IISE than in control eyes (p fibre layer (RNFL) was significantly thicker in eyes with IISE and NISE than in control eyes in both horizontal and vertical meridians (all p < 0.001). Ganglion cell-inner plexiform layer (GCIPL) thickness showed a weak positive correlation with vision, and RNFL thickness showed a weak negative correlation with vision and visual field extent. Based on these results, the inner retina, including the GCIPL and RNFL, maintains its gross integrity longer than the photoreceptor layer in RP. Additionally, thickening of the inner retina may have some functional implications in patients with RP. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Interleukin-6 Deficiency Attenuates Retinal Ganglion Cell Axonopathy and Glaucoma-Related Vision Loss

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    Franklin D. Echevarria

    2017-05-01

    Full Text Available The pleotropic cytokine interleukin-6 (IL-6 is implicated in retinal ganglion cell (RGC survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT and IL-6 knock-out mice (B6;129S2-IL6tm1kopf/J; IL-6-/- after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model. IOP increased by 20% following microbead injection in both genotypes (p < 0.05. However, deficits in wound healing at the site of corneal injection were noted. In WT mice, elevated IOP produced degenerating axon profiles and decreased axon density in the optic nerve by 15% (p < 0.01. In IL-6-/- mice, axon density in the optic nerve did not differ between microbead- and saline-injected mice (p > 0.05 and degenerating axon profiles were minimal. Preservation of RGC axons was reflected in visual function, where visual acuity decreased significantly in a time-dependent manner with microbead-induced IOP elevation in WT (p < 0.001, but not IL-6-/- mice (p > 0.05. Despite this preservation of RGC axons and visual acuity, both microbead-injected WT and IL-6-/- mice exhibited a 50% decrease in anterograde CTB transport to the superior colliculus, as compared to saline-injected controls (p < 0.01. Assessment of glial reactivity revealed no genotype- or IOP-dependent changes in retinal astrocytes. IOP elevation decreased microglia density and percent retinal area covered in WT mice (p < 0.05, while IL-6-/- mice exhibited only a decrease in density (p < 0.05. Together, our findings indicate that two defining features of RGC axonopathy—axon transport deficits and structural degeneration of

  10. Asymmetric inheritance of the apical domain and self-renewal of retinal ganglion cell progenitors depend on Anillin function.

    Science.gov (United States)

    Paolini, Alessio; Duchemin, Anne-Laure; Albadri, Shahad; Patzel, Eva; Bornhorst, Dorothee; González Avalos, Paula; Lemke, Steffen; Machate, Anja; Brand, Michael; Sel, Saadettin; Di Donato, Vincenzo; Del Bene, Filippo; Zolessi, Flavio R; Ramialison, Mirana; Poggi, Lucia

    2015-03-01

    Divisions that generate one neuronal lineage-committed and one self-renewing cell maintain the balance of proliferation and differentiation for the generation of neuronal diversity. The asymmetric inheritance of apical domains and components of the cell division machinery has been implicated in this process, and might involve interactions with cell fate determinants in regulatory feedback loops of an as yet unknown nature. Here, we report the dynamics of Anillin - an essential F-actin regulator and furrow component - and its contribution to progenitor cell divisions in the developing zebrafish retina. We find that asymmetrically dividing retinal ganglion cell progenitors position the Anillin-rich midbody at the apical domain of the differentiating daughter. anillin hypomorphic conditions disrupt asymmetric apical domain inheritance and affect daughter cell fate. Consequently, the retinal cell type composition is profoundly affected, such that the ganglion cell layer is dramatically expanded. This study provides the first in vivo evidence for the requirement of Anillin during asymmetric neurogenic divisions. It also provides insights into a reciprocal regulation between Anillin and the ganglion cell fate determinant Ath5, suggesting a mechanism whereby the balance of proliferation and differentiation is accomplished during progenitor cell divisions in vivo. © 2015. Published by The Company of Biologists Ltd.

  11. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

    Science.gov (United States)

    Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

    2016-05-01

    CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

  12. Orexin-A potentiates L-type calcium/barium currents in rat retinal ganglion cells.

    Science.gov (United States)

    Liu, F; Weng, S-J; Yang, X-L; Zhong, Y-M

    2015-10-01

    Two neuropeptides, orexin-A and orexin-B (also called hypocretin-1 and -2), have been implicated in sleep/wake regulation, feeding behaviors via the activation of two subtypes of G-protein-coupled receptors: orexin 1 and orexin 2 receptors (OX1R and OX2R). While the expression of orexins and orexin receptors is immunohistochemically revealed in retinal neurons, the function of these peptides in the retina is largely unknown. Using whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that orexin-A increased L-type-like barium currents (IBa,L) in ganglion cells (GCs), and the effect was blocked by the selective OX1R antagonist SB334867, but not by the OX2R antagonist TCS OX2 29. The orexin-A effect was abolished by intracellular dialysis of GDP-β-S/GPAnt-2A, a Gq protein inhibitor, suggesting the mediation of Gq. Additionally, during internal dialysis of the phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor U73122, orexin-A did not change the IBa,L of GCs, whereas the orexin-A effect persisted in the presence of the phosphatidylcholine (PC)-PLC inhibitor D609. The orexin-A-induced potentiation was not seen with internal infusion of Ca(2+)-free solution or when inositol 1,4,5-trisphosphate (IP3)-sensitive Ca(2+) release from intracellular stores was blocked by heparin/xestospongins-C. Moreover, the orexin-A effect was mimicked by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, but was eliminated when PKC was inhibited by bisindolylmaleimide IV (Bis-IV)/Gö6976. Neither adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) nor guanosine 3',5'-cyclic monophosphate (cGMP)-protein kinase G (PKG) signaling pathway was likely involved, as orexin-A persisted to potentiate the IBa,L of GCs no matter these two pathways were activated or inhibited. These results suggest that, by activating OX1R, orexin-A potentiates the IBa,L of rat GCs through a distinct Gq/PI-PLC/IP3/Ca(2+)/PKC signaling pathway. Copyright

  13. Hydrostatic pressure does not cause detectable changes in survival of human retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Andrew Osborne

    Full Text Available PURPOSE: Elevated intraocular pressure (IOP is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP. The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC survival in the human retina was investigated. METHODS: A chamber was designed to expose cells to increased HP (constant and fluctuating. Accurate pressure control (10-100 mmHg was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs from donor eyes (<24 h post mortem were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD. Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1 and RGC number by immunohistochemistry (NeuN. Activated p38 and JNK were detected by Western blot. RESULTS: Exposure of HORCs to constant (60 mmHg or fluctuating (10-100 mmHg; 1 cycle/min pressure for 24 or 48 h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1 or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24 h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100 mmHg; 1 cycle/min for 15, 30, 60 and 90 min durations, whereas OGD (3 h increased activation of p38 and JNK, remaining elevated for 90 min post-OGD. CONCLUSIONS: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina.

  14. Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica.

    Science.gov (United States)

    Hu, Sai-Jing; Lu, Pei-Rong

    2018-01-01

    To determine the thickness of the retinal ganglion cell-inner plexiform layer (GCIPL) and the retinal nerve fiber layer (RNFL) in patients with neuromyelitis optica (NMO). We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis (ON), subjects were divided into either the NMO-ON group (30 eyes) or the NMO-ON contra group (10 eyes). A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using high-definition optical coherence tomography (OCT). In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 µm, the minimum GCIPL thickness was 66.02±10.02 µm, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 µm in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±17.09 µm, the minimum GCIPL thickness was 25.39±25.1 µm, and the RNFL thicknesses were 148.33±23.22, 126.36±23.45, 82.21±22.30 and 83.36±31.28 µm in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 µm, the minimum GCIPL thickness was 85.28±10.75 µm, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 µm in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group ( P deviation (MD) and corrected pattern standard deviation (PSD) in the NMO-ON group ( P <0.05). The thickness of the GCIPL and RNFL, as measured using OCT, may indicate optic nerve damage in patients with NMO.

  15. Retinal ganglion cell complex changes using spectral domain optical coherence tomography in diabetic patients without retinopathy

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    Ahmed I. Hegazy

    2017-03-01

    Full Text Available AIM: To assess the ganglion cell complex (GCC thickness in diabetic eyes without retinopathy. METHODS: Two groups included 45 diabetic eyes without retinopathy and 21 non diabetic eyes. All subjects underwent full medical and ophthalmological history, full ophthalmological examination, measuring GCC thickness and central foveal thickness (CFT using the RTVue® spectral domain-optical coherence tomography (SD-OCT, and HbA1C level. RESULTS: GCC focal loss volume (FLV% was significantly more in diabetic eyes (22.2% below normal than normal eyes (P=0.024. No statistically significant difference was found between the diabetic group and the control group regarding GCC global loss volume (GLV% (P=0.160. CFT was positively correlated to the average, superior and inferior GCC (P=0.001, 0.000 and 0.001 respectively and negatively correlated to GLV% and FLV% (P=0.002 and 0.031 respectively in diabetic eyes. C/D ratio in diabetic eyes was negatively correlated to average, superior and inferior GCC (P=0.015, 0.007 and 0.017 respectively. The FLV% was negatively correlated to the refraction and level of HbA1c (P=0.019 and 0.013 respectively and positively correlated to the best corrected visual acuity (BCVA in logMAR in diabetic group (P=0.004. CONCLUSION: Significant GCC thinning in diabetes predates retinal vasculopathy, which is mainly focal rather than diffuse. It has no preference to either the superior or inferior halves of the macula. Increase of myopic error is significantly accompanied with increased focal GCC loss. GCC loss is accompanied with increased C/D ratio in diabetic eyes.

  16. Retinal ganglion cell neuroprotection in a rat model of glaucoma following brimonidine, latanoprost or combined treatments.

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    Hernández, María; Urcola, J Haritz; Vecino, Elena

    2008-05-01

    The aim of the present study is to evaluate the neuroprotective effect of two antiglaucomatous substances, regardless of their hypotensive effect in the eye. Brimonidine, which does not reduce IOP when administered intraperitoneally, and latanoprost, which has a renowned hypotensive effect topically. We examined rat retinal ganglion cell (RGC) survival and size distribution in experimental glaucoma in response to different glaucomatous agents. IOP was elevated by episcleral vein cauterization (EVC) prior to the application of different treatments: (I) PBS application (control group), (II) intraperitoneal administration of brimonidine (a general hypotensive agent), (III) topical application of latanoprost (an ocular hypotensive agent), and (IV) latanoprost combined with brimonidine. After 12 weeks, RGCs were retrogradely labeled with fluorogold and RGC density was analyzed. EVC caused a significant increase (42%) in IOP in each group before drug treatment. After 12weeks of EVC, RGC survival in control vs. EVC rats was 78.9+/-3.2%. No IOP reduction was observed in brimonidine injected rats, but RGC survival at 12 weeks was total (103.7+/-2.7%). In latanoprost treated rats, IOP dropped by around 22% and 94.7+/-3.7% of the RGC population survived. Finally in the latanoprost+brimonidine combined group, IOP was significantly reduced by 25% and 94.4+/-2.2% of RGCs survived. Surprisingly, whereas EVC led to a 6% increase in RGC soma size, brimonidine treatment was associated with a 9% reduction in the soma size of RGCs at 12 weeks. We conclude that brimonidine exerts a neuroprotective effect via a mechanism which is independent of IOP reduction. These findings indicate that cell survival in glaucoma may be enhanced by neuroprotective strategies which are independent of IOP reduction. No synergistic neuroprotective effect was observed when both treatments were applied simultaneously.

  17. Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

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    Nicole Purrier

    Full Text Available Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods. Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

  18. Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage

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    Kumar Anil

    2010-10-01

    Full Text Available Abstract Background The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6 plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis. Results We have shown that RGCs exposed to hypoxia (1% or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM, revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6. Conclusion Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.

  19. Temporal response properties of retinal ganglion cells in rd1 mice evoked by amplitude-modulated electrical pulse trains.

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    Ryu, Sang Baek; Ye, Jang Hee; Goo, Yong Sook; Kim, Chi Hyun; Kim, Kyung Hwan

    2010-12-01

    The electrophysiological properties of degenerated retinas responding to amplitude-modulated electrical pulse trains were investigated to provide a guideline for the development of a stimulation strategy for retinal prostheses. The activities of retinal ganglion cells (RGCs) in response to amplitude-modulated pulse trains were recorded from an in vitro model of retinal prosthesis, which consisted of an rd1 mouse retinal patch attached to a planar multielectrode array. The ability of the population activities of RGCs to effectively represent, or encode, the information on the visual intensity time series, when the intensity of visual input is transformed to pulse amplitudes, was investigated. An optimal pulse amplitude range was selected so that RGC firing rates increased monotonically and linearly. An approximately 10-Hz rhythm was observed in the field potentials from degenerated retinas, which resulted in a rhythmic burst of spontaneous spikes. Multiple peaks were present in poststimulus time histograms, with interpeak intervals corresponding to the oscillation frequency of the field potentials. Phase resetting of the field potential oscillation by stimulation was consistently observed. Despite a prominent alteration of the properties of electrically evoked firing with respect to normal retinas, RGC response strengths could be modulated by pulse amplitude. Accordingly, the temporal information of stimulation could be faithfully represented in the RGC firing patterns by an amplitude-modulated pulse train. The results suggest that pulse amplitude modulation is a feasible means of implementing a stimulation strategy for retinal prostheses, despite the marked change in the physiological properties of RGCs in degenerated retinas.

  20. Baclofen Protects Primary Rat Retinal Ganglion Cells from Chemical Hypoxia-Induced Apoptosis through the Akt and PERK Pathways

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    Pingping Fu

    2016-11-01

    Full Text Available Retinal ganglion cells (RGCs consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABAB receptor agonist, of retinal ganglion cells against hypoxia-induced apoptosis. CoCl2 was applied to mimic hypoxia. Primary rat retinal ganglion cells (RGCs were subjected to CoCl2 with or without baclofen treatment, and RNA interference techniques were used to knock down the GABAB2 gene in the primary RGCs. The viability and apoptosis of RGCs were assessed using cell viability and TUNEL assays, Hoechst staining, and flow cytometry. The expression of cleaved caspase-3, bcl-2, bax, Akt, phospho-Akt, PERK, phospho-PERK, eIF2α, phospho-eIF2α, ATF-4, and CHOP were measured using western blotting. GABAB2 mRNA expression was determined using quantitative real-time polymerase chain reaction (qRT-PCR analysis. Our study revealed that CoCl2 significantly induced RGC apoptosis and that baclofen reversed these effects. CoCl2-induced reduction of Akt activity was also reversed by baclofen. Baclofen prevented the activation of the PERK pathway and the increase in CHOP expression induced by CoCl2. Knockdown of GABAB2 and the inactivation of the Akt pathway by inhibitors reduced the protective effect of baclofen on CoCl2-treated RGCs. Taken together, these results demonstrate that baclofen protects RGCs from CoCl2-induced apoptosis by increasing Akt activity and by suppressing the PERK pathway and CHOP activation.

  1. Neuroprotection of rat retinal ganglion cells mediated through alpha7 nicotinic acetylcholine receptors.

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    Iwamoto, K; Mata, D; Linn, D M; Linn, C L

    2013-05-01

    Glutamate-induced excitotoxicity is thought to play an important role in several neurodegenerative diseases in the central nervous system (CNS). In this study, neuroprotection against glutamate-induced excitotoxicity was analyzed using acetylcholine (ACh), nicotine and the α7 specific nicotinic acetylcholine receptor (α7 nAChR) agonist, N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), in cultured adult rat retinal neurons. Adult Long Evans rat retinas were dissociated and retinal ganglion cells (RGCs) were isolated from all other retinal tissue using a two-step panning technique. Once isolated, RGCs were cultured under various pharmacological conditions to demonstrate excitotoxicity and neuroprotection against excitotoxicity. After 3 days, RGCs were immunostained with antibodies against the glycoprotein, Thy 1.1, counted and cell survival was assessed relative to control untreated conditions. 500 μM glutamate induced excitotoxicity in large and small RGCs in an adult rat dissociated culture. After 3 days in culture with glutamate, the cell survival of large RGCs decreased by an average of 48.16% while the cell survival of small RGCs decreased by an average of 42.03%. Using specific glutamate receptor agonists and antagonists, we provide evidence that the excitotoxic response was mediated through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid (KA) and N-methyl-d-aspartate (NMDA) glutamate receptors through an apoptotic mechanism. However, the excitotoxic effect of glutamate on all RGCs was eliminated if cells were cultured for an hour with 10 μM ACh, 100 μM nicotine or 100 nM of the α7 nAChR agonist, PNU-282987, before the glutamate insult. Inhibition studies using 10nM methyllycaconitine (MLA) or α-bungarotoxin (α-Bgt) supported the hypothesis that neuroprotection against glutamate-induced excitotoxicity on rat RGCs was mediated through α7 nAChRs. In immunocytochemical studies, double

  2. Macular ganglion cell complex and retinal nerve fiber layer comparison in different stages of age-related macular degeneration.

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    Zucchiatti, Ilaria; Parodi, Maurizio Battaglia; Pierro, Luisa; Cicinelli, Maria Vittoria; Gagliardi, Marco; Castellino, Niccolò; Bandello, Francesco

    2015-09-01

    To employ optical coherence tomography (OCT) to analyze the morphologic changes in the inner retina in different categories of age-related macular degeneration (AMD). Observational cross-sectional study. Single-center study. Inclusion criteria were age over 50, diagnosis of Age-Related Eye Disease Study (AREDS) category 2 and 3, naïve neovascular AMD, and atrophic AMD. Healthy patients of similar age acted as a control group. Primary outcome measures were the changes in ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). Secondary outcomes included modifications of rim area and cup-to-disc ratio. One hundred and thirty eyes of 130 patients were recruited: 26 eyes for AREDS category 2, 26 for AREDS category 3, 26 for neovascular AMD, 26 with atrophic AMD, and 26 controls. Mean peripapillary RNFL thickness was significantly lower in neovascular AMD, compared to controls (P = .004); peripapillary RNFL did not significantly vary among AREDS category 2 and 3 and atrophic AMD groups, compared to controls. Mean GCC thickness was higher in the control group, becoming progressively thinner up to neovascular and atrophic AMD groups (P < .0001). Rim area was significantly thinner in the neovascular AMD group compared with controls (P = .047); cup-to-disc ratio was higher in the neovascular AMD group compared with the control group (P = .047). This study demonstrates that eyes with neovascular AMD display reduced RNFL and GCC thickness. RNFL is partially spared in atrophic advanced AMD. The identification of alteration in RNFL and GCC thickness may reveal useful for future therapeutic implications. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Retinal ganglion cells: mechanisms underlying depolarization block and differential responses to high frequency electrical stimulation of ON and OFF cells

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    Kameneva, T.; Maturana, M. I.; Hadjinicolaou, A. E.; Cloherty, S. L.; Ibbotson, M. R.; Grayden, D. B.; Burkitt, A. N.; Meffin, H.

    2016-02-01

    Objective. ON and OFF retinal ganglion cells (RGCs) are known to have non-monotonic responses to increasing amplitudes of high frequency (2 kHz) biphasic electrical stimulation. That is, an increase in stimulation amplitude causes an increase in the cell’s spike rate up to a peak value above which further increases in stimulation amplitude cause the cell to decrease its activity. The peak response for ON and OFF cells occurs at different stimulation amplitudes, which allows differential stimulation of these functional cell types. In this study, we investigate the mechanisms underlying the non-monotonic responses of ON and OFF brisk-transient RGCs and the mechanisms underlying their differential responses. Approach. Using in vitro patch-clamp recordings from rat RGCs, together with simulations of single and multiple compartment Hodgkin-Huxley models, we show that the non-monotonic response to increasing amplitudes of stimulation is due to depolarization block, a change in the membrane potential that prevents the cell from generating action potentials. Main results. We show that the onset for depolarization block depends on the amplitude and frequency of stimulation and reveal the biophysical mechanisms that lead to depolarization block during high frequency stimulation. Our results indicate that differences in transmembrane potassium conductance lead to shifts of the stimulus currents that generate peak spike rates, suggesting that the differential responses of ON and OFF cells may be due to differences in the expression of this current type. We also show that the length of the axon’s high sodium channel band (SOCB) affects non-monotonic responses and the stimulation amplitude that leads to the peak spike rate, suggesting that the length of the SOCB is shorter in ON cells. Significance. This may have important implications for stimulation strategies in visual prostheses.

  4. The intricacies of neurotrophic factor therapy for retinal ganglion cell rescue in glaucoma: a case for gene therapy

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    Marianna Foldvari

    2016-01-01

    Full Text Available Regeneration of damaged retinal ganglion cells (RGC and their axons is an important aspect of reversing vision loss in glaucoma patients. While current therapies can effectively lower intraocular pressure, they do not provide extrinsic support to RGCs to actively aid in their protection and regeneration. The unmet need could be addressed by neurotrophic factor gene therapy, where plasmid DNA, encoding neurotrophic factors, is delivered to retinal cells to maintain sufficient levels of neurotrophins in the retina. In this review, we aim to describe the intricacies in the design of the therapy including: the choice of neurotrophic factor, the site and route of administration and target cell populations for gene delivery. Furthermore, we also discuss the challenges currently being faced in RGC-related therapy development with special considerations to the existence of multiple RGC subtypes and the lack of efficient and representative in vitro models for rapid and reliable screening in the drug development process.

  5. Isolation and Molecular Profiling of Primary Mouse Retinal Ganglion Cells: Comparison of Phenotypes from Healthy and Glaucomatous Retinas.

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    Chintalapudi, Sumana R; Djenderedjian, Levon; Stiemke, Andrew B; Steinle, Jena J; Jablonski, Monica M; Morales-Tirado, Vanessa M

    2016-01-01

    Loss of functional retinal ganglion cells (RGC) is an element of retinal degeneration that is poorly understood. This is in part due to the lack of a reliable and validated protocol for the isolation of primary RGCs. Here we optimize a feasible, reproducible, standardized flow cytometry-based protocol for the isolation and enrichment of homogeneous RGC with the Thy1.2(hi)CD48(neg)CD15(neg)CD57(neg) surface phenotype. A three-step validation process was performed by: (1) genomic profiling of 25-genes associated with retinal cells; (2) intracellular labeling of homogeneous sorted cells for the intracellular RGC-markers SNCG, brain-specific homeobox/POU domain protein 3A (BRN3A), TUJ1, and RNA-binding protein with multiple splicing (RBPMS); and (3) by applying the methodology on RGC from a mouse model with elevated intraocular pressure (IOP) and optic nerve damage. Use of primary RGC cultures will allow for future careful assessment of important cell specific pathways in RGC to provide mechanistic insights into the declining of visual acuity in aged populations and those suffering from retinal neurodegenerative diseases.

  6. Isolation and Molecular Profiling of Primary Mouse Retinal Ganglion Cells: Comparison of Phenotypes from Healthy and Glaucomatous Retinas

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    Chintalapudi, Sumana R.; Djenderedjian, Levon; Stiemke, Andrew B.; Steinle, Jena J.; Jablonski, Monica M.; Morales-Tirado, Vanessa M.

    2016-01-01

    Loss of functional retinal ganglion cells (RGC) is an element of retinal degeneration that is poorly understood. This is in part due to the lack of a reliable and validated protocol for the isolation of primary RGCs. Here we optimize a feasible, reproducible, standardized flow cytometry-based protocol for the isolation and enrichment of homogeneous RGC with the Thy1.2hiCD48negCD15negCD57neg surface phenotype. A three-step validation process was performed by: (1) genomic profiling of 25-genes associated with retinal cells; (2) intracellular labeling of homogeneous sorted cells for the intracellular RGC-markers SNCG, brain-specific homeobox/POU domain protein 3A (BRN3A), TUJ1, and RNA-binding protein with multiple splicing (RBPMS); and (3) by applying the methodology on RGC from a mouse model with elevated intraocular pressure (IOP) and optic nerve damage. Use of primary RGC cultures will allow for future careful assessment of important cell specific pathways in RGC to provide mechanistic insights into the declining of visual acuity in aged populations and those suffering from retinal neurodegenerative diseases. PMID:27242509

  7. Selectivity of direct and network-mediated stimulation of the retinal ganglion cells with epi-, sub- and intraretinal electrodes

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    Boinagrov, David; Pangratz-Fuehrer, Susanne; Goetz, Georges; Palanker, Daniel

    2014-04-01

    Objective. Intra-retinal placement of stimulating electrodes can provide close and stable proximity to target neurons. We assessed improvement in stimulation thresholds and selectivity of the direct and network-mediated retinal stimulation with intraretinal electrodes, compared to epiretinal and subretinal placements. Approach. Stimulation thresholds of the retinal ganglion cells (RGCs) in wild-type rat retina were measured using the patch-clamp technique. Direct and network-mediated responses were discriminated using various synaptic blockers. Main results. Three types of RGC responses were identified: short latency (SL, τ 40 ms) originating in photoreceptors. Cathodic epiretinal stimulation exhibited the lowest threshold for direct RGC response and the highest direct selectivity (network/direct thresholds ratio), exceeding a factor of 3 with pulse durations below 0.5 ms. For network-mediated stimulation, the lowest threshold was obtained with anodic pulses in OPL position, and its network selectivity (direct/network thresholds ratio) increased with pulse duration, exceeding a factor of 4 at 10 ms. Latency of all three types of responses decreased with increasing strength of the stimulus. Significance. These results define the optimal range of pulse durations, pulse polarities and electrode placement for the retinal prostheses aiming at direct or network-mediated stimulation of RGCs.

  8. Delayed neurogenesis leads to altered specification of ventrotemporal retinal ganglion cells in albino mice

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    2014-01-01

    Background Proper binocular vision depends on the routing at the optic chiasm of the correct proportion of retinal ganglion cell (RGC) axons that project to the same (ipsilateral) and opposite (contralateral) side of the brain. The ipsilateral RGC projection is reduced in mammals with albinism, a congenital disorder characterized by deficient pigmentation in the skin, hair, and eyes. Compared to the pigmented embryonic mouse retina, the albino embryonic mouse retina has fewer RGCs that express the zinc-finger transcription factor, Zic2, which is transiently expressed by RGCs fated to project ipsilaterally. Here, using Zic2 as a marker of ipsilateral RGCs, Islet2 as a marker of contralateral RGCs, and birthdating, we investigate spatiotemporal dynamics of RGC production as they relate to the phenotype of diminished ipsilateral RGC number in the albino retina. Results At embryonic day (E)15.5, fewer Zic2-positive (Zic2+) RGCs are found in the albino ventrotemporal (VT) retina compared with the pigmented VT retina, as we previously reported. However, the reduction in Zic2+ RGCs in the albino is not accompanied by a compensatory increase in Zic2-negative (Zic2−) RGCs, resulting in fewer RGCs in the VT retina at this time point. At E17.5, however, the number of RGCs in the VT region is similar in pigmented and albino retinae, implicating a shift in the timing of RGC production in the albino. Short-term birthdating assays reveal a delay in RGC production in the albino VT retina between E13 and E15. Specifically, fewer Zic2+ RGCs are born at E13 and more Zic2− RGCs are born at E15. Consistent with an increase in the production of Zic2− RGCs born at later ages, more RGCs at E17.5 express the contralateral marker, Islet2, in the albino VT retina compared with the pigmented retina. Conclusions A delay in neurogenesis in the albino retina is linked to the alteration of RGC subtype specification and consequently leads to the reduced ipsilateral projection that

  9. Dre - Cre sequential recombination provides new tools for retinal ganglion cell labeling and manipulation in mice.

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    Szilard Sajgo

    Full Text Available BACKGROUND: Genetic targeting methods have greatly advanced our understanding of many of the 20 Retinal Ganglion Cell (RGC types conveying visual information from the eyes to the brain. However, the complexity and partial overlap of gene expression patterns in RGCs call for genetic intersectional or sparse labeling strategies. Loci carrying the Cre recombinase in conjunction with conditional knock-out, reporter or other genetic tools can be used for targeted cell type ablation and functional manipulation of specific cell populations. The three members of the Pou4f family of transcription factors, Brn3a, Brn3b and Brn3c, expressed early during RGC development and in combinatorial pattern amongst RGC types are excellent candidates for such gene manipulations. METHODS AND FINDINGS: We generated conditional Cre knock-in alleles at the Brn3a and Brn3b loci, Brn3a(CKOCre and Brn3b(CKOCre. When crossed to mice expressing the Dre recombinase, the endogenous Brn3 gene expressed by Brn3a(CKOCre or Brn3b(CKOCre is removed and replaced with a Cre recombinase, generating Brn3a(Cre and Brn3b(Cre knock-in alleles. Surprisingly both Brn3a(Cre and Brn3b(Cre knock-in alleles induce early ubiquitous recombination, consistent with germline expression. However in later stages of development, their expression is limited to the expected endogenous pattern of the Brn3a and Brn3b genes. We use the Brn3a(Cre and Brn3b(Cre alleles to target a Cre dependent Adeno Associated Virus (AAV reporter to RGCs and demonstrate its use in morphological characterization, early postnatal gene delivery and tracing the expression of Brn3 genes in RGCs. CONCLUSIONS: Dre recombinase effectively recombines the Brn3a(CKOCre and Brn3b(CKOCre alleles containing its roxP target sites. Sequential Dre to Cre recombination reveals Brn3a and Brn3b expression in early mouse development. The generated Brn3a(Cre and Brn3b(Cre alleles are useful tools that can target exogenously delivered Cre dependent

  10. Effect of SIRT1 regulating cholesterol synthesis in repairing retinal ganglion cells after optic nerve injury in rats

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    Yan Zhang

    2014-10-01

    Full Text Available AIM: To investigate the repair mechanism associated with cholesterol synthesis regulated by silent information regulator 1(SIRT1in rat model of optic nerve damage. METHODS: Preparation of optic nerve damage in 70 rats was randomly divided into normal group(10 rats, resveratrol treatment group(experimental group 30 ratsand PBS buffer control group(30 rats. The experimental group and control group was further divided into 3 subgroups(each group 10 rats, respectively. After 7, 14, 21d injected resveratrol or PBS, optic nerve injury were observed, then the rats were sacrificed. Retina was segregated; the surviving retinal ganglion cell(RGCswas counted. Dissection of optic nerve, cholesterol content of them were tested; RT-PCR was used to detect mRNA expression of SIRT1, SREBP2 and HMGCR; Western blot assay was used to test the protein expression levels of SIRT1, cholesterol regulatory element binding protein 2(SREBP2and HMGCR. RESULTS: The numbers of RGCs and cholesterol levels of rat model with optic nerve injury decreased significantly(PPPPCONCLUSION: Up-regulating the expression of SIRT1, SREBP2 and down-regulating HMGCR by resveratrol could repair the injury of optic nerve through promoting the synthesis of cholesterol in neurons and retinal ganglion cells in the repair process. SIRT1 may be as a promising new target for treatment on optic nerve damage.

  11. Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica

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    Sai-Jing Hu

    2018-01-01

    Full Text Available AIM: To determine the thickness of the retinal ganglion cell-inner plexiform layer (GCIPL and the retinal nerve fiber layer (RNFL in patients with neuromyelitis optica (NMO. METHODS: We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis (ON, subjects were divided into either the NMO-ON group (30 eyes or the NMO-ON contra group (10 eyes. A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using high-definition optical coherence tomography (OCT. RESULTS: In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 μm, the minimum GCIPL thickness was 66.02±10.02 μm, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 μm in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±17.09 μm, the minimum GCIPL thickness was 25.39±25.1 μm, and the RNFL thicknesses were 148.33±23.22, 126.36±23.45, 82.21±22.30 and 83.36±31.28 μm in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 μm, the minimum GCIPL thickness was 85.28±10.75 μm, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 μm in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group (P<0.05; additionally, the RNFL was thinner in the inferior quadrant in the NMO-ON group than in the control group (P<0.05. Significant correlations were observed between the GCIPL and RNFL thickness measurements as well as between thickness measurements and the two visual field parameters of mean deviation (MD and corrected pattern standard deviation (PSD in the NMO-ON group (P<0.05. CONCLUSION: The thickness of the GCIPL

  12. Differential calcium signaling mediated by voltage-gated calcium channels in rat retinal ganglion cells and their unmyelinated axons.

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    Allison Sargoy

    Full Text Available Aberrant calcium regulation has been implicated as a causative factor in the degeneration of retinal ganglion cells (RGCs in numerous injury models of optic neuropathy. Since calcium has dual roles in maintaining homeostasis and triggering apoptotic pathways in healthy and injured cells, respectively, investigation of voltage-gated Ca channel (VGCC regulation as a potential strategy to reduce the loss of RGCs is warranted. The accessibility and structure of the retina provide advantages for the investigation of the mechanisms of calcium signalling in both the somata of ganglion cells as well as their unmyelinated axons. The goal of the present study was to determine the distribution of VGCC subtypes in the cell bodies and axons of ganglion cells in the normal retina and to define their contribution to calcium signals in these cellular compartments. We report L-type Ca channel α1C and α1D subunit immunoreactivity in rat RGC somata and axons. The N-type Ca channel α1B subunit was in RGC somata and axons, while the P/Q-type Ca channel α1A subunit was only in the RGC somata. We patch clamped isolated ganglion cells and biophysically identified T-type Ca channels. Calcium imaging studies of RGCs in wholemounted retinas showed that selective Ca channel antagonists reduced depolarization-evoked calcium signals mediated by L-, N-, P/Q- and T-type Ca channels in the cell bodies but only by L-type Ca channels in the axons. This differential contribution of VGCC subtypes to calcium signals in RGC somata and their axons may provide insight into the development of target-specific strategies to spare the loss of RGCs and their axons following injury.

  13. Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina.

    Science.gov (United States)

    Galindo-Romero, Caridad; Harun-Or-Rashid, Mohammad; Jiménez-López, Manuel; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Hallböök, Finn

    2016-01-01

    We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5-10 μg NMDA caused 30-50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina.

  14. Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina

    Science.gov (United States)

    Galindo-Romero, Caridad; Harun-Or-Rashid, Mohammad; Jiménez-López, Manuel; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

    2016-01-01

    We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5–10 μg NMDA caused 30–50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina. PMID:27611432

  15. Activation and inhibition of retinal ganglion cells in response to epiretinal electrical stimulation: a computational modelling study

    Science.gov (United States)

    Abramian, Miganoosh; Lovell, Nigel H.; Morley, John W.; Suaning, Gregg J.; Dokos, Socrates

    2015-02-01

    Objective. Retinal prosthetic devices aim to restore sight in visually impaired people by means of electrical stimulation of surviving retinal ganglion cells (RGCs). This modelling study aims to demonstrate that RGC inhibition caused by high-intensity cathodic pulses greatly influences their responses to epiretinal electrical stimulation and to investigate the impact of this inhibition on spatial activation profiles as well as their implications for retinal prosthetic device design. Another aim is to take advantage of this inhibition to reduce axonal activation in the nerve fibre layer. Approach. A three-dimensional finite-element model of epiretinal electrical stimulation was utilized to obtain RGC activation and inhibition threshold profiles for a range of parameters. Main results. RGC activation and inhibition thresholds were highly dependent on cell and stimulus parameters. Activation thresholds were 1.5, 3.4 and 11.3 μA for monopolar electrodes with 5, 20 and 50 μm radii, respectively. Inhibition to activation threshold ratios were mostly within the range 2-10. Inhibition significantly altered spatial patterns of RGC activation. With concentric electrodes and appropriately high levels of stimulus amplitudes, activation of passing axons was greatly reduced. Significance. RGC inhibition significantly impacts their spatial activation profiles, and therefore it most likely influences patterns of perceived phosphenes induced by retinal prosthetic devices. Thus this inhibition should be taken into account in future studies concerning retinal prosthesis development. It might be possible to utilize this inhibitory effect to bypass activation of passing axons and selectively stimulate RGCs near their somas and dendrites to achieve more localized phosphenes.

  16. Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion.

    Science.gov (United States)

    Hadj-Saïd, Wahiba; Froger, Nicolas; Ivkovic, Ivana; Jiménez-López, Manuel; Dubus, Élisabeth; Dégardin-Chicaud, Julie; Simonutti, Manuel; Quénol, César; Neveux, Nathalie; Villegas-Pérez, María Paz; Agudo-Barriuso, Marta; Vidal-Sanz, Manuel; Sahel, Jose-Alain; Picaud, Serge; García-Ayuso, Diego

    2016-09-01

    Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S- and L- cones) in an animal model of induced taurine depletion. We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a+ RGCs, and L- and S-opsin+ cones was automatically quantified and their retinal distribution studied using isodensity maps. The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. S-opsin+cones were more affected (36%) than L-opsin+cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed. This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin+cones, L-opsin+cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.

  17. Negative impact of rAAV2 mediated expression of SOCS3 on the regeneration of adult retinal ganglion cell axons

    NARCIS (Netherlands)

    Hellstrom, M.; Muhling, J.; Ehlert, E.M.; Verhaagen, J.; Pollett, M.A.; Hu, Y.; Harvey, A.R.

    2011-01-01

    Intravitreal injections of recombinant ciliary neurotrophic factor (rCNTF) protect adult rat retinal ganglion cells (RGCs) after injury and stimulate regeneration, an effect enhanced by co-injection with a cAMP analogue (CPT-cAMP). This effect is partly mediated by PKA and associated signaling

  18. Lentiviral-mediated transfer of CNTF to schwann cells within reconstructed peripheral nerve grafts enhances adult retinal ganglion cell survival and axonal regeneration

    NARCIS (Netherlands)

    Hu, Ying; Leaver, Simone G; Plant, Giles W; Hendriks, William T J; Niclou, Simone P; Verhaagen, J.; Harvey, Alan R; Cui, Qi

    We recently described a method for reconstituting peripheral nerve (PN) sheaths using adult Schwann cells (SCs). Reconstructed PN tissue grafted onto the cut optic nerve supports the regeneration of injured adult rat retinal ganglion cell (RGC) axons. To determine whether genetic manipulation of

  19. Detection of macular ganglion cell loss in preperimetric glaucoma patients with localized retinal nerve fibre defects by spectral-domain optical coherence tomography.

    Science.gov (United States)

    Na, Jung Hwa; Lee, Kyoungsub; Lee, Jong Rak; Baek, Seunghee; Yoo, Sung Jun; Kook, Michael S

    2013-12-01

    To evaluate and compare the utility of ganglion cell complex with peripapillary retinal nerve fibre layer and optic nerve head measurements for detection of localized defects in patients with preperimetric glaucoma using spectral-domain optical coherence tomography. Prospective study. Preperimetric glaucoma patients. A total of 105 eyes with preperimetric glaucoma and 68 age- and refractive error-matched control eyes were enrolled. The ability to detect localized retinal nerve fibre layer defects by RTVue-100 spectral-domain optical coherence tomography (Optovue, Inc., Fremont, CA, USA) was assessed calculating the areas under receiver operating characteristic curves. The ability to detect localized retinal nerve fibre layer defects by spectral-domain optical coherence tomography. Global volume loss and superior ganglion cell complex thickness showed the largest area under receiver operating characteristic curve values (both areas under receiver operating characteristic curves 0.84, P fibre layer thickness afforded the best diagnostic capability (area under receiver operating characteristic curve 0.89, P optic nerve head parameters, the horizontal cup:disc ratio yielded the highest area under receiver operating characteristic curve (0.85, P fibre layer, and optic nerve head) (P > 0.02). Ganglion cell complex thickness was significantly reduced in eyes with preperimetric glaucoma. Ganglion cell complex imaging using spectral-domain optical coherence tomography may be a useful ancillary modality for detection of early macular changes in glaucomatous eyes with localized retinal nerve fibre layer defects. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

  20. Neuronal injury external to the retina rapidly activates retinal glia, followed by elevation of markers for cell cycle re-entry and death in retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Alba Galan

    Full Text Available Retinal ganglion cells (RGCs are neurons that relay visual signals from the retina to the brain. The RGC cell bodies reside in the retina and their fibers form the optic nerve. Full transection (axotomy of the optic nerve is an extra-retinal injury model of RGC degeneration. Optic nerve transection permits time-kinetic studies of neurodegenerative mechanisms in neurons and resident glia of the retina, the early events of which are reported here. One day after injury, and before atrophy of RGC cell bodies was apparent, glia had increased levels of phospho-Akt, phospho-S6, and phospho-ERK1/2; however, these signals were not detected in injured RGCs. Three days after injury there were increased levels of phospho-Rb and cyclin A proteins detected in RGCs, whereas these signals were not detected in glia. DNA hyperploidy was also detected in RGCs, indicative of cell cycle re-entry by these post-mitotic neurons. These events culminated in RGC death, which is delayed by pharmacological inhibition of the MAPK/ERK pathway. Our data show that a remote injury to RGC axons rapidly conveys a signal that activates retinal glia, followed by RGC cell cycle re-entry, DNA hyperploidy, and neuronal death that is delayed by preventing glial MAPK/ERK activation. These results demonstrate that complex and variable neuro-glia interactions regulate healthy and injured states in the adult mammalian retina.

  1. Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate.

    Science.gov (United States)

    Wu, Fuguo; Kaczynski, Tadeusz J; Sethuramanujam, Santhosh; Li, Renzhong; Jain, Varsha; Slaughter, Malcolm; Mu, Xiuqian

    2015-03-31

    As with other retinal cell types, retinal ganglion cells (RGCs) arise from multipotent retinal progenitor cells (RPCs), and their formation is regulated by a hierarchical gene-regulatory network (GRN). Within this GRN, three transcription factors--atonal homolog 7 (Atoh7), POU domain, class 4, transcription factor 2 (Pou4f2), and insulin gene enhancer protein 1 (Isl1)--occupy key node positions at two different stages of RGC development. Atoh7 is upstream and is required for RPCs to gain competence for an RGC fate, whereas Pou4f2 and Isl1 are downstream and regulate RGC differentiation. However, the genetic and molecular basis for the specification of the RGC fate, a key step in RGC development, remains unclear. Here we report that ectopic expression of Pou4f2 and Isl1 in the Atoh7-null retina using a binary knockin-transgenic system is sufficient for the specification of the RGC fate. The RGCs thus formed are largely normal in gene expression, survive to postnatal stages, and are physiologically functional. Our results indicate that Pou4f2 and Isl1 compose a minimally sufficient regulatory core for the RGC fate. We further conclude that during development a core group of limited transcription factors, including Pou4f2 and Isl1, function downstream of Atoh7 to determine the RGC fate and initiate RGC differentiation.

  2. Retinofugal Projections from Melanopsin-Expressing Retinal Ganglion Cells Revealed by Intraocular Injections of Cre-Dependent Virus.

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    Anton Delwig

    Full Text Available To understand visual functions mediated by intrinsically photosensitive melanopsin-expressing retinal ganglion cells (mRGCs, it is important to elucidate axonal projections from these cells into the brain. Initial studies reported that melanopsin is expressed only in retinal ganglion cells within the eye. However, recent studies in Opn4-Cre mice revealed Cre-mediated marker expression in multiple brain areas. These discoveries complicate the use of melanopsin-driven genetic labeling techniques to identify retinofugal projections specifically from mRGCs. To restrict labeling to mRGCs, we developed a recombinant adeno-associated virus (AAV carrying a Cre-dependent reporter (human placental alkaline phosphatase that was injected into the vitreous of Opn4-Cre mouse eyes. The labeling observed in the brain of these mice was necessarily restricted specifically to retinofugal projections from mRGCs in the injected eye. We found that mRGCs innervate multiple nuclei in the basal forebrain, hypothalamus, amygdala, thalamus and midbrain. Midline structures tended to be bilaterally innervated, whereas the lateral structures received mostly contralateral innervation. As validation of our approach, we found projection patterns largely corresponded with previously published results; however, we have also identified a few novel targets. Our discovery of projections to the central amygdala suggests a possible direct neural pathway for aversive responses to light in neonates. In addition, projections to the accessory optic system suggest that mRGCs play a direct role in visual tracking, responses that were previously attributed to other classes of retinal ganglion cells. Moreover, projections to the zona incerta raise the possibility that mRGCs could regulate visceral and sensory functions. However, additional studies are needed to investigate the actual photosensitivity of mRGCs that project to the different brain areas. Also, there is a concern of "overlabeling

  3. Strychnine blocks transient but not sustained inhibition in mudpuppy retinal ganglion cells.

    Science.gov (United States)

    Belgum, J H; Dvorak, D R; McReynolds, J S

    1984-01-01

    Transient and sustained inhibitory synaptic inputs to on-centre, off-centre, and on-off ganglion cells in the mudpuppy retina were studied using intracellular recording in the superfused eye-cup preparation. When chemical transmission was blocked with 4 mM-Co2+, application of either glycine or gamma-aminobutyric acid (GABA) caused a hyperpolarization and conductance increase in all ganglion cells. For both amino acids, the responses were dose dependent in the range 0.05-10 mM, with a half-maximal response at about 0.7 mM. Glycine and GABA sensitivities were very similar in all three types of ganglion cells. The response to applied glycine was selectively antagonized by 10(-5) M-strychnine and the response to applied GABA was selectively antagonized by 10(-5) M-picrotoxin. In all ganglion cells, 10(-5) M-strychnine eliminated the transient inhibitory events which occur at the onset and termination of a light stimulus. The block of transient inhibition was associated with a relative depolarization of membrane potential and decrease in conductance at these times. Strychnine had no effect on membrane potential or conductance in darkness or during sustained inhibitory responses to light. Picrotoxin (10(-5) M) did not block transient inhibitory events in any ganglion cells, but did affect other components of their responses. The results suggest that in all three classes of ganglion cells transient inhibition, but not sustained inhibition, may be mediated by glycine or a closely related substance. PMID:6481635

  4. Spatially restricted electrical activation of retinal ganglion cells in the rabbit retina by hexapolar electrode return configuration

    Science.gov (United States)

    Habib, Amgad G.; Cameron, Morven A.; Suaning, Gregg J.; Lovell, Nigel H.; Morley, John W.

    2013-06-01

    Objective. Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed ‘phosphenes’. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration. Approach. Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally. Main results. Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation. Significance. The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.

  5. Matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells

    DEFF Research Database (Denmark)

    Gaublomme, Djoere; Buyens, Tom; De Groef, Lies

    2014-01-01

    , we were able to show that broad-spectrum MMP inhibition reduces axon outgrowth of mouse retinal ganglion cells (RGCs), implicating MMPs as beneficial factors in axonal regeneration. Additional studies, using more specific MMP inhibitors and MMP-deficient mice, disclosed that both MMP-2 and MT1-MMP......, but not MMP-9, are involved in this process. Furthermore, administration of a novel antibody to MT1-MMP that selectively blocks pro-MMP-2 activation revealed a functional co-involvement of these proteinases in determining RGC axon outgrowth. Subsequent immunostainings showed expression of both MMP-2 and MT1......-MMP in RGC axons and glial cells. Finally, results from combined inhibition of MMP-2 and β1-integrin were suggestive for a functional interaction between these molecules. Overall, our data indicate MMP-2 and MT1-MMP as promising axonal outgrowth-promoting molecules. Axonal regeneration in the central...

  6. Patterns of Retinal Ganglion Cell Damage in Neurodegenerative Disorders: Parvocellular vs Magnocellular Degeneration in Optical Coherence Tomography Studies

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    Chiara La Morgia

    2017-12-01

    Full Text Available Many neurodegenerative disorders, such as Parkinson’s disease (PD and Alzheimer’s disease (AD, are characterized by loss of retinal ganglion cells (RGCs as part of the neurodegenerative process. Optical coherence tomography (OCT studies demonstrated variable degree of optic atrophy in these diseases. However, the pattern of degenerative changes affecting the optic nerve (ON can be different. In particular, neurodegeneration is more evident for magnocellular RGCs in AD and multiple system atrophy with a pattern resembling glaucoma. Conversely, in PD and Huntington’s disease, the parvocellular RGCs are more vulnerable. This latter pattern closely resembles that of mitochondrial optic neuropathies, possibly pointing to similar pathogenic mechanisms. In this review, the currently available evidences on OCT findings in these neurodegenerative disorders are summarized with particular emphasis on the different pattern of RGC loss. The ON degeneration could become a validated biomarker of the disease, which may turn useful to follow natural history and possibly assess therapeutic efficacy.

  7. The influence of venous blood flow on the retinal ganglion cell complex in patients with primary open angle glaucoma

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    N. I. Kurysheva

    2014-07-01

    Full Text Available Purpose: To study the influence of venous blood flow on the ganglion cell complex (GCC in patients with preperimetric and perimetric open angle glaucoma.Methods: 74 patients were included in the research. 59 eyes and 62 eyes were diagnosed with preperimetric and perimetric open angle glaucoma respectively. The mean age was 56.5±10.5 years. 22 (12 female and 10 male healthy individuals constituted the control group. The ganglion cell complex and retinal nerve fibre layer were evaluated with the help of optical coherence tomography (RTVue-100 OCT, Optovue, Inc., Fremont, CA. Ocular blood flow was measured by Color Doppler Imaging (multifunctional VOLUSON 730 ProSystem. The statistical analysis included correlation between GCC and RNFL thickness in both glaucoma groups.Results: The results showed a statistically significant reduction of venous blood flow velocity in both glaucoma groups compared to the control group. No difference in venous blood flow parameters between two glaucoma groups was found, except resistance index, which was higher in perimetric group in comparison to preperimetric group. A correlation was also obtained between venous blood flow parameters and GCC and RNFL thickness in both glaucoma groups.Conclusion: Early GCC damage in glaucoma might occur due to venous blood flow reduction. This fact may be of great value in understanding glaucoma pathogenesis and search for novel treatment options.

  8. Effect of Extracellular Zinc Chelator on Rat Retinal Ganglion Cell Number, and Taurine and Zinc Transporters in These Cells

    Directory of Open Access Journals (Sweden)

    Asarí Márquez García

    2017-05-01

    Full Text Available Zinc deficiency in humans causes decreased antioxidants in the retina and is related with abnormal darkness adaptation, cataracts, blindness, and macular degeneration. There is little information about the effects of zinc on the taurine system in mammalian retinal cells. Therefore, we studied the effect of zinc on the taurine transporter (TAUT and zinc transporters (ZnT-1 and 3 using the extracellular zinc chelator, diethylenetriaminepentaacetic acid (DTPA by fluorescence immunocytochemistry and immunohistochemistry in the ganglion cells (CG and cell layers of the retina of rats. Three days after administration of DTPA (10µM primary antibodies and secondary antibodies conjugated with rhodamine or fluorescein isothiocyanate (FITC were used as required. For immunocytochemical labeling approximately three hundred cells per condition were counted. For immunohistochemical labeling, the fluorescence intensity was measured as integrated optical density (DOI in four areas for each layer of tissue. DTPA produced a decrease of 32 % and 29 % in GC of the total cells labeled with antibody against glycoprotein Thy 1.1 and γ-synuclein, respectively. It also produced a significant decrease in TAUT localization in 27 and 28 % compared to controls. DTPA produced a decrease in the localization of ZnT-1 and ZnT-3 in the retina layers (ganglion cells, GCC and the outer and inner plexiform, CEP and CIP. The study of these molecules in the retina is relevant to understanding the interactions of taurine and zinc in this structure.

  9. Effect of myopia on ganglion cell complex and peripapillary retinal nerve fibre layer measurements: a Fourier-domain optical coherence tomography study of young Chinese persons.

    Science.gov (United States)

    Zhao, Zhennan; Jiang, Chunhui

    2013-08-01

    To investigate the change of the ganglion cell complex and peripapillary retinal nerve fibre layer under different refractive conditions, as measured by optical coherence tomography. Cross-sectional observational study. A total of 107 eyes from 107 subjects were studied. Ganglion cell complex and retinal nerve fibre layer were studied by a spectral-domain system. Their relationship against spherical equivalents and axial length was studied. The thickness of ganglion cell complex and retinal nerve fibre layer at different area and under different refractive conditions as measurements by optical coherence tomography. The average, superior and inferior macular ganglion cell complex thickness was significantly associated with both spherical equivalents (all P fibre layer thicknesses from the superior, inferior and temporal quadrants were associated with both spherical equivalents (all P fibre layer thickness was studied in sections, then some parts of the upper and lower temporal part showed no correlation with either spherical equivalents or axial length (all P fibre layer were correlated with refraction and axial length. Therefore, when using these for clinical purposes, attention must be paid to the refractive state of the patient. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

  10. Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF.

    Science.gov (United States)

    Wong, Wai-Kai; Cheung, Anny Wan-Suen; Yu, Sau-Wai; Sha, Ou; Cho, Eric Yu Pang

    2014-10-01

    Different trophic factors are known to promote retinal ganglion cell survival and regeneration, but each had their own limitations. We report that hepatocyte growth factor (HGF) confers distinct advantages in supporting ganglion cell survival and axonal regeneration, when compared to two well-established trophic factors ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Ganglion cells in adult hamster were injured by cutting the optic nerve. HGF, CNTF, or BDNF was injected at different dosages intravitreally after injury. Ganglion cell survival was quantified at 7, 14, or 28 days postinjury. Peripheral nerve (PN) grafting to the cut optic nerve of the growth factor-injected eye was performed either immediately after injury or delayed until 7 days post-injury. Expression of heat-shock protein 27 and changes in microglia numbers were quantified in different growth factor groups. The cellular distribution of c-Met in the retina was examined by anti-c-Met immunostaining. Hepatocyte Growth Factor (HGF) was equally potent as BDNF in promoting short-term survival (up to 14 days post-injury) and also supported survival at 28 days post-injury when ganglion cells treated by CNTF or BDNF failed to be sustained. When grafting was performed without delay, HGF stimulated twice the number of axons to regenerate compared with control but was less potent than CNTF. However, in PN grafting delayed for 7 days after optic nerve injury, HGF maintained a better propensity of ganglion cells to regenerate than CNTF. Unlike CNTF, HGF application did not increase HSP27 expression in ganglion cells. Microglia proliferation was prolonged in HGF-treated retinas compared with CNTF or BDNF. C-Met was localized to both ganglion cells and Muller cells, suggesting HGF could be neuroprotective via interacting with both neurons and glia. Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to

  11. miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells

    Science.gov (United States)

    Cheng, Li-Bo; Li, Ke-ran; Yi, Nan; Li, Xiu-miao; Wang, Feng; Xue, Bo; Pan, Ying-shun; Yao, Jin; Jiang, Qin; Wu, Zhi-feng

    2017-01-01

    Activation of NF-E2-related factor 2 (Nrf2) signaling could protect cells from ultra violet (UV) radiation. We aim to provoke Nrf2 activation via downregulating its inhibitor Keap1 by microRNA-141 (“miR-141”). In both human retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs), forced-expression of miR-141 downregulated Keap1, causing Nrf2 stabilization, accumulation and nuclear translocation, which led to transcription of multiple antioxidant-responsive element (ARE) genes (HO1, NOQ1 and GCLC). Further, UV-induced reactive oxygen species (ROS) production and cell death were significantly attenuated in miR-141-expressing RPEs and RGCs. On the other hand, depletion of miR-141 via expressing its inhibitor antagomiR-141 led to Keap1 upregulation and Nrf2 degradation, which aggravated UV-induced death of RPEs and RGCs. Significantly, Nrf2 shRNA knockdown almost abolished miR-141-mediated cytoprotection against UV in RPEs. These results demonstrate that miR-141 targets Keap1 to activate Nrf2 signaling, which protects RPEs and RGCs from UV radiation. PMID:28061435

  12. Light-induced fos expression in intrinsically photosensitive retinal ganglion cells in melanopsin knockout (opn4 mice.

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    Gary E Pickard

    Full Text Available Retinal ganglion cells that express the photopigment melanopsin are intrinsically photosensitive (ipRGCs and exhibit robust synaptically driven ON-responses to light, yet they will continue to depolarize in response to light when all synaptic input from rod and cone photoreceptors is removed. The light-evoked increase in firing of classical ganglion cells is determined by synaptic input from ON-bipolar cells in the proximal sublamina of the inner plexiform layer. OFF-bipolar cells synapse with ganglion cell dendrites in the distal sublamina of the inner plexiform layer. Of the several types of ipRGC that have been described, M1 ipRGCs send dendrites exclusively into the OFF region of the inner plexiform layer where they stratify near the border of the inner nuclear layer. We tested whether M1 ipRGCs with dendrites restricted to the OFF sublamina of the inner plexiform layer receive synaptic ON-bipolar input by examining light-induced gene expression in vivo using melanopsin knockout mice. Mice in which both copies of the melanopsin gene (opn4 have been replaced with the tau-lacZ gene (homozygous tau-lacZ(+/+ knockin mice are melanopsin knockouts (opn4(-/- but M1 ipRGCs are specifically identified by their expression of beta-galactosidase. Approximately 60% of M1 ipRGCs in Opn4(-/- mice exposed to 3 hrs of light expressed c-Fos; no beta-galactosidase-positive RGCs expressed c-Fos in the dark. Intraocular application of L-AP4, a compound which blocks transmission of visual signals between photoreceptors and ON-bipolar cells significantly reduced light-evoked c-Fos expression in M1 ipRGCs compared to saline injected eyes (66% saline vs 27% L-AP4. The results are the first description of a light-evoked response in an ipRGC lacking melanopsin and provide in vivo confirmation of previous in vitro observations illustrating an unusual circuit in the retina in which ganglion cells sending dendrites to the OFF sublamina of the inner plexiform layer

  13. CD146- and CD105-positive phenotypes of retinal ganglion cells. Are these in situ proofs of neuronal regeneration?

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    Vrapciu, A D; Rusu, M C; Voinea, L M; Corbu, C G

    2014-10-01

    The in vivo identity of stem cells is not yet clear. Numerous studies involve the perivascular niches as providers of stem cells during regenerative processes. CD146, in humans, as well as gicerin, at chicken, play roles in neuronal development and neurites extension. CD146 is a marker of stemness but also a pericytary marker. Stem cells in vascular niches can differentiate in neural cells. By applying CD146 and CD105 antibodies on human retinas from glaucomatous eyes, CD146-positive retinal ganglion cells (RGCs) were found, some being placed in perivascular positions; ongoing processes of neurites extension were related to these neurons. On other hand, RGCs were positively labeled by CD105 antibodies. These results support the hypothesis that in glaucoma eyes the CD146-positive RGCs result from regenerative processes driven by stem cells in the retinal perivascular niches. Further experiments are needed to evaluate whether CR146-positive neurons indicate also a physiological process of maintenance of retina. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses.

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    Megumi Hatori

    Full Text Available Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR, and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diphtheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals.

  15. Molecular mechanisms of retinal ganglion cell degeneration in glaucoma and future prospects for cell body and axonal protection

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    Yasunari eMunemasa

    2013-01-01

    Full Text Available Glaucoma, which affects more than 70 million people worldwide, is a heterogeneous group of disorders with a resultant common denominator; optic neuropathy, eventually leading to irreversible blindness. The clinical manifestations of primary open-angle glaucoma (POAG, the most common subtype of glaucoma, include excavation of the optic disc and progressive loss of visual field. Axonal degeneration of retinal ganglion cells (RGCs and apoptotic death of their cell bodies are observed in glaucoma, in which the reduction of intraocular pressure is known to slow progression of the disease. A pattern of localized retinal nerve fiber layer defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. The mechanisms of degeneration of neuronal cell bodies and their axons may differ. In this review, we addressed the molecular mechanisms of cell body death and axonal degeneration in glaucoma and proposed axonal protection in addition to cell body protection. The concept of axonal protection may become a new therapeutic strategy to prevent further axonal degeneration or revive dying axons in patients with preperimetric glaucoma. Further study will be needed to clarify whether the combination therapy of axonal protection and cell body protection will have greater protective effects in early or progressive glaucomatous optic neuropathy.

  16. Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response

    Science.gov (United States)

    Yeh, Connie Y.; Koehl, Kristin L.; Harman, Christine D.; Iwabe, Simone; Guzman, José M.; Petersen-Jones, Simon M.; Kardon, Randy H.; Komáromy, András M.

    2017-01-01

    Purpose The purpose of this study was to evaluate a chromatic pupillometry protocol for specific functional assessment of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in dogs. Methods Chromatic pupillometry was tested and compared in 37 dogs in different stages of primary loss of rod, cone, and combined rod/cone and optic nerve function, and in 5 wild-type (WT) dogs. Eyes were stimulated with 1-s flashes of dim (1 cd/m2) and bright (400 cd/m2) blue light (for scotopic conditions) or bright red (400 cd/m2) light with 25-cd/m2 blue background (for photopic conditions). Canine retinal melanopsin/Opn4 was cloned, and its expression was evaluated using real-time quantitative reverse transcription-PCR and immunohistochemistry. Results Mean ± SD percentage of pupil constriction amplitudes induced by scotopic dim blue (scDB), scotopic bright blue (scBB), and photopic bright red (phBR) lights in WT dogs were 21.3% ± 10.6%, 50.0% ± 17.5%, and 19.4% ± 7.4%, respectively. Melanopsin-mediated responses to scBB persisted for several minutes (7.7 ± 4.6 min) after stimulus offset. In dogs with inherited retinal degeneration, loss of rod function resulted in absent scDB responses, followed by decreased phBR responses with disease progression and loss of cone function. Primary loss of cone function abolished phBR responses but preserved those responses to blue light (scDB and scBB). Although melanopsin/Opn4 expression was diminished with retinal degeneration, melanopsin-expressing ipRGCs were identified for the first time in both WT and degenerated canine retinas. Conclusions Pupil responses elicited by light stimuli of different colors and intensities allowed differential functional assessment of canine rods, cones, and ipRGCs. Chromatic pupillometry offers an effective tool for diagnosing retinal and optic nerve diseases. PMID:28061512

  17. EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

    Science.gov (United States)

    Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

    2017-07-01

    To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

  18. Neuroprotection of a novel cyclopeptide C*HSDGIC* from the cyclization of PACAP (1-5 in cellular and rodent models of retinal ganglion cell apoptosis.

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    Huanhuan Cheng

    Full Text Available To investigate the protective effects of a novel cyclopeptide C*HSDGIC* (CHC from the cyclization of Pituitary adenylate cyclase-activating polypeptide (PACAP (1-5 in cellular and rodent models of retinal ganglion cell apoptosis.Double-labeling immunohistochemistry was used to detect the expression of Thy-1 and PACAP receptor type 1 in a retinal ganglion cell line RGC-5. The apoptosis of RGC-5 cells was induced by 0.02 J/cm(2 Ultraviolet B irradiation. MTT assay, flow cytometry, fluorescence microscopy were used to investigate the viability, the level of reactive oxygen species (ROS and apoptosis of RGC-5 cells respectively. CHC attenuated apoptotic cell death induced by Ultraviolet B irradiation and inhibited the excessive generation of ROS. Moreover, CHC treatment resulted in decreased expression of Bax and concomitant increase of Bcl-2, as was revealed by western-blot analysis. The in vivo apoptosis of retinal ganglion cells was induced by injecting 50 mM N-methyl-D-aspartate (NMDA (100 nmol in a 2 µL saline solution intravitreally, and different dosages of CHC were administered. At day 7, rats in CHC+ NMDA-treated groups showed obvious aversion to light when compared to NMDA rats. Electroretinogram recordings revealed a marked decrease in the amplitudes of a-wave, b-wave, and photopic negative response due to NMDA damage. In retina receiving intravitreal NMDA and CHC co-treatment, these values were significantly increased. CHC treatment also resulted in less NMDA-induced cell loss and a decrease in the proportion of dUTP end-labeling-positive cells in ganglion cell line.C*HSDGIC*, a novel cyclopeptide from PACAP (1-5 attenuates apoptosis in RGC-5 cells and inhibits NMDA-induced retinal neuronal death. The beneficial effects may occur via the mitochondria pathway. PACAP derivatives like CHC may serve as a promising candidate for neuroprotection in glaucoma.

  19. Comparison of diagnostic capability of macular ganglion cell complex and retinal nerve fiber layer among primary open angle glaucoma, ocular hypertension, and normal population using Fourier-domain optical coherence tomography and determining their functional correlation in Indian population

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    Nabanita Barua

    2016-01-01

    Full Text Available Context: Analysis of diagnostic ability of macular ganglionic cell complex and retinal nerve fiber layer (RNFL in glaucoma. Aim: To correlate functional and structural parameters and comparing predictive value of each of the structural parameters using Fourier-domain (FD optical coherence tomography (OCT among primary open angle glaucoma (POAG and ocular hypertension (OHT versus normal population. Setting and Design: Single centric, cross-sectional study done in 234 eyes. Materials and Methods: Patients were enrolled in three groups: POAG, ocular hypertensive and normal (40 patients in each group. After comprehensive ophthalmological examination, patients underwent standard automated perimetry and FD-OCT scan in optic nerve head and ganglion cell mode. The relationship was assessed by correlating ganglion cell complex (GCC parameters with mean deviation. Results were compared with RNFL parameters. Statistical Analysis: Data were analyzed with SPSS, analysis of variance, t-test, Pearson′s coefficient, and receiver operating curve. Results: All parameters showed strong correlation with visual field (P 0.5 when compared with other parameters. None of the parameters showed significant diagnostic capability to detect OHT from normal population. In diagnosing early glaucoma from OHT and normal population, only inferior GCC had statistically significant AUC value (0.715. Conclusion: In this study, GCC and RNFL parameters showed equal predictive capability in perimetric versus normal group. In early stage, inferior GCC was the best parameter. In OHT population, single day cross-sectional imaging was not valuable.

  20. Quercetin Declines Apoptosis, Ameliorates Mitochondrial Function and Improves Retinal Ganglion Cell Survival and Function in In Vivo Model of Glaucoma in Rat and Retinal Ganglion Cell Culture In Vitro

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    Feng-Juan Gao

    2017-09-01

    Full Text Available Glaucoma is a progressive neuropathy characterized by the loss of retinal ganglion cells (RGCs. Strategies that delay or halt RGC loss have been recognized as potentially beneficial for rescuing vision in glaucoma patients. Quercetin (Qcn is a natural and important dietary flavonoid compound, widely distributed in fruits and vegetables. Mounting evidence suggests that Qcn has numerous neuroprotective effects. However, whether Qcn exerts neuroprotective effects on RGC in glaucoma is poorly understood. In this study, we investigated the protective effect of Qcn against RGC damage in a rat chronic ocular hypertension (COHT model invivo and hypoxia-induced primary cultured RGC damage in vitro, and we further explored the underlying neuroprotective mechanisms. We found that Qcn not only improved RGC survival and function from a very early stage of COHT invivo, it promoted the survival of hypoxia-treated primary cultured RGCs invitro via ameliorating mitochondrial function and preventing mitochondria-mediated apoptosis. Our findings suggest that Qcn has direct protective effects on RGCs that are independent of lowering the intraocular pressure (IOP. Qcn may be a promising therapeutic agent for improving RGC survival and function in glaucomatous neurodegeneration.

  1. Glaucomatous progression in the retinal nerve fibre and retinal ganglion cell-inner plexiform layers determined using optical coherence tomography-guided progression analysis.

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    Hwang, Young Hoon; Kim, Yeji; Chung, Jae Keun; Lee, Kwan Bok

    2018-02-01

    To investigate the characteristics of glaucomatous progression in circumpapillary retinal nerve fibre layer (RNFL) and macular retinal ganglion cell-inner plexiform layer (GCIPL) determined using optical coherence tomography-guided progression analysis (OCT-GPA). Serial OCT images of 527 glaucomatous eyes with greater than four OCT tests were screened. Among them, 106 (20.1 per cent) eyes with progression in either RNFL or GCIPL determined using OCT-GPA were included. Based on the agreement of progression detection between RNFL and GCIPL, the eyes were classified into the 'RNFL progression earlier group', 'GCIPL progression earlier group', or 'simultaneous progression group'. The type of progression was classified as diffuse, localised or mixed. Among the 106 eyes with progression, 100 (94.3 per cent) showed RNFL progression and 83 (78.3 per cent) showed GCIPL progression. Fifty-four (50.9 per cent), 13 (12.3 per cent), and 39 (36.8 per cent) eyes were classified into the RNFL progression earlier group, GCIPL progression earlier group, and simultaneous progression group, respectively. Diffuse-type progression was found in three (three per cent) eyes with RNFL progression and 32 (38.6 per cent) eyes with GCIPL progression. The most common location of progression was the 7 o'clock sector (42.0 per cent) in the RNFL and the inferotemporal sector (39.8 per cent) in the GCIPL. The most common characteristic of RNFL and GCIPL progression determined using OCT-GPA was localised thinning in the inferotemporal area. Progression was more frequently found in the RNFL than in the GCIPL, and diffuse-type progression was more frequent in the GCIPL than in the RNFL. © 2018 Optometry Australia.

  2. Single cell transcriptome profiling of developing chick retinal cells.

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    Laboissonniere, Lauren A; Martin, Gregory M; Goetz, Jillian J; Bi, Ran; Pope, Brock; Weinand, Kallie; Ellson, Laura; Fru, Diane; Lee, Miranda; Wester, Andrea K; Liu, Peng; Trimarchi, Jeffrey M

    2017-08-15

    The vertebrate retina is a specialized photosensitive tissue comprised of six neuronal and one glial cell types, each of which develops in prescribed proportions at overlapping timepoints from a common progenitor pool. While each of these cells has a specific function contributing to proper vision in the mature animal, their differential representation in the retina as well as the presence of distinctive cellular subtypes makes identifying the transcriptomic signatures that lead to each retinal cell's fate determination and development challenging. We have analyzed transcriptomes from individual cells isolated from the chick retina throughout retinogenesis. While we focused our efforts on the retinal ganglion cells, our transcriptomes of developing chick cells also contained representation from multiple retinal cell types, including photoreceptors and interneurons at different stages of development. Most interesting was the identification of transcriptomes from individual mixed lineage progenitor cells in the chick as these cells offer a window into the cell fate decision-making process. Taken together, these data sets will enable us to uncover the most critical genes acting in the steps of cell fate determination and early differentiation of various retinal cell types. © 2017 Wiley Periodicals, Inc.

  3. T-box transcription regulator Tbr2 is essential for the formation and maintenance of Opn4/melanopsin-expressing intrinsically photosensitive retinal ganglion cells.

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    Mao, Chai-An; Li, Hongyan; Zhang, Zhijing; Kiyama, Takae; Panda, Satchidananda; Hattar, Samer; Ribelayga, Christophe P; Mills, Stephen L; Wang, Steven W

    2014-09-24

    Opsin 4 (Opn4)/melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) play a major role in non-image-forming visual system. Although advances have been made in understanding their morphological features and functions, the molecular mechanisms that regulate their formation and survival remain unknown. Previously, we found that mouse T-box brain 2 (Tbr2) (also known as Eomes), a T-box-containing transcription factor, was expressed in a subset of newborn RGCs, suggesting that it is involved in the formation of specific RGC subtypes. In this in vivo study, we used complex mouse genetics, single-cell dye tracing, and behavioral analyses to determine whether Tbr2 regulates ipRGC formation and survival. Our results show the following: (1) Opn4 is expressed exclusively in Tbr2-positive RGCs; (2) no ipRGCs are detected when Tbr2 is genetically ablated before RGC specification; and (3) most ipRGCs are eliminated when Tbr2 is deleted in established ipRGCs. The few remaining ipRGCs display abnormal dendritic morphological features and functions. In addition, some Tbr2-expressing RGCs can activate Opn4 expression on the loss of native ipRGCs, suggesting that Tbr2-expressing RGCs may serve as a reservoir of ipRGCs to regulate the number of ipRGCs and the expression levels of Opn4. Copyright © 2014 the authors 0270-6474/14/3413083-13$15.00/0.

  4. Multipronged approach to identify and validate a novel upstream regulator of Sncg in mouse retinal ganglion cells.

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    Chintalapudi, Sumana R; Morales-Tirado, Vanessa M; Williams, Robert W; Jablonski, Monica M

    2016-02-01

    Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Mechanistic studies on RGCs are hindered by the lack of sufficient primary cells and consensus regarding their signature markers. Recently, γ-synuclein (SNCG) has been shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the role of Sncg in RGCs, we used a novel systems genetics approach to identify a gene that modulates Sncg expression, followed by confirmatory studies in both healthy and diseased retinae. We found that chromosome 1 harbors an expression quantitative trait locus that modulates Sncg expression in the mouse retina, and identified the prefoldin-2 (PFDN2) gene as the candidate upstream modulator of Sncg expression. Our immunohistochemical analyses revealed similar expression patterns in both mouse and human healthy retinae, with PFDN2 colocalizing with SNCG in RGCs and their axons. In contrast, in retinae from glaucoma subjects, SNCG levels were significantly reduced, although PFDN2 levels were maintained. Using a novel flow cytometry-based RGC isolation method, we obtained viable populations of murine RGCs. Knocking down Pfdn2 expression in primary murine RGCs significantly reduced Sncg expression, confirming that Pfdn2 regulates Sncg expression in murine RGCs. Gene Ontology analysis indicated shared mitochondrial function associated with Sncg and Pfdn2. These data solidify the relationship between Sncg and Pfdn2 in RGCs, and provide a novel mechanism for maintaining RGC health. © 2015 FEBS.

  5. Characterization of retinal ganglion cell, horizontal cell, and amacrine cell types expressing the neurotrophic receptor tyrosine kinase Ret.

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    Parmhans, Nadia; Sajgo, Szilard; Niu, Jingwen; Luo, Wenqin; Badea, Tudor Constantin

    2018-03-01

    We report the retinal expression pattern of Ret, a receptor tyrosine kinase for the glial derived neurotrophic factor (GDNF) family ligands (GFLs), during development and in the adult mouse. Ret is initially expressed in retinal ganglion cells (RGCs), followed by horizontal cells (HCs) and amacrine cells (ACs), beginning with the early stages of postmitotic development. Ret expression persists in all three classes of neurons in the adult. Using RNA sequencing, immunostaining and random sparse recombination, we show that Ret is expressed in at least three distinct types of ACs, and ten types of RGCs. Using intersectional genetics, we describe the dendritic arbor morphologies of RGC types expressing Ret in combination with each of the three members of the POU4f/Brn3 family of transcription factors. Ret expression overlaps with Brn3a in 4 RGC types, with Brn3b in 5 RGC types, and with Brn3c in one RGC type, respectively. Ret + RGCs project to the lateral geniculate nucleus (LGN), pretectal area (PTA) and superior colliculus (SC), and avoid the suprachiasmatic nucleus and accessory optic system. Brn3a + Ret + and Brn3c + Ret + RGCs project preferentially to contralateral retinorecipient areas, while Brn3b + Ret + RGCs shows minor ipsilateral projections to the olivary pretectal nucleus and the LGN. Our findings establish intersectional genetic approaches for the anatomic and developmental characterization of individual Ret + RGC types. In addition, they provide necessary information for addressing the potential interplay between GDNF neurotrophic signaling and transcriptional regulation in RGC type specification. © 2017 Wiley Periodicals, Inc.

  6. Protection by an oral disubstituted hydroxylamine derivative against loss of retinal ganglion cell differentiation following optic nerve crush.

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    James D Lindsey

    Full Text Available Thy-1 is a cell surface protein that is expressed during the differentiation of retinal ganglion cells (RGCs. Optic nerve injury induces progressive loss in the number of RGCs expressing Thy-1. The rate of this loss is fastest during the first week after optic nerve injury and slower in subsequent weeks. This study was undertaken to determine whether oral treatment with a water-soluble N-hydroxy-2,2,6,6-tetramethylpiperidine derivative (OT-440 protects against loss of Thy-1 promoter activation following optic nerve crush and whether this effect targets the earlier quick phase or the later slow phase. The retina of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice was imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO. These mice then received oral OT-440 prepared in cream cheese or dissolved in water, or plain vehicle, for two weeks and were imaged again prior to unilateral optic nerve crush. Treatments and weekly imaging continued for four more weeks. Fluorescent neurons were counted in the same defined retinal areas imaged at each time point in a masked fashion. When the counts at each time point were directly compared, the numbers of fluorescent cells at each time point were greater in the animals that received OT-440 in cream cheese by 8%, 27%, 52% and 60% than in corresponding control animals at 1, 2, 3 and 4 weeks after optic nerve crush. Similar results were obtained when the vehicle was water. Rate analysis indicated the protective effect of OT-440 was greatest during the first two weeks and was maintained in the second two weeks after crush for both the cream cheese vehicle study and water vehicle study. Because most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 can either protect against or delay early degenerative responses occurring in RGCs following optic nerve injury.

  7. Substituting mouse transcription factor Pou4f2 with a sea urchin orthologue restores retinal ganglion cell development.

    Science.gov (United States)

    Mao, Chai-An; Agca, Cavit; Mocko-Strand, Julie A; Wang, Jing; Ullrich-Lüter, Esther; Pan, Ping; Wang, Steven W; Arnone, Maria Ina; Frishman, Laura J; Klein, William H

    2016-03-16

    Pou domain transcription factor Pou4f2 is essential for the development of retinal ganglion cells (RGCs) in the vertebrate retina. A distant orthologue of Pou4f2 exists in the genome of the sea urchin (class Echinoidea) Strongylocentrotus purpuratus (SpPou4f1/2), yet the photosensory structure of sea urchins is strikingly different from that of the mammalian retina. Sea urchins have no obvious eyes, but have photoreceptors clustered around their tube feet disc. The mechanisms that are associated with the development and function of photoreception in sea urchins are largely unexplored. As an initial approach to better understand the sea urchin photosensory structure and relate it to the mammalian retina, we asked whether SpPou4f1/2 could support RGC development in the absence of Pou4f2. To answer this question, we replaced genomic Pou4f2 with an SpPou4f1/2 cDNA. In Pou4f2-null mice, retinas expressing SpPou4f1/2 were outwardly identical to those of wild-type mice. SpPou4f1/2 retinas exhibited dark-adapted electroretinogram scotopic threshold responses, indicating functionally active RGCs. During retinal development, SpPou4f1/2 activated RGC-specific genes and in S. purpuratus, SpPou4f2 was expressed in photoreceptor cells of tube feet in a pattern distinct from Opsin4 and Pax6. Our results suggest that SpPou4f1/2 and Pou4f2 share conserved components of a gene network for photosensory development and they maintain their conserved intrinsic functions despite vast morphological differences in mouse and sea urchin photosensory structures. © 2016 The Authors.

  8. Gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model.

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    Martin, Keith R G; Quigley, Harry A; Zack, Donald J; Levkovitch-Verbin, Hana; Kielczewski, Jennifer; Valenta, Danielle; Baumrind, Lisa; Pease, Mary Ellen; Klein, Ronald L; Hauswirth, William W

    2003-10-01

    To develop a modified adenoassociated viral (AAV) vector capable of efficient transfection of retinal ganglion cells (RGCs) and to test the hypothesis that use of this vector to express brain-derived neurotrophic factor (BDNF) could be protective in experimental glaucoma. Ninety-three rats received one unilateral, intravitreal injection of either normal saline (n = 30), AAV-BDNF-woodchuck hepatitis posttranscriptional regulatory element (WPRE; n = 30), or AAV-green fluorescent protein (GFP)-WPRE (n = 33). Two weeks later, experimental glaucoma was induced in the injected eye by laser application to the trabecular meshwork. Survival of RGCs was estimated by counting axons in optic nerve cross sections after 4 weeks of glaucoma. Transgene expression was assessed by immunohistochemistry, Western blot analysis, and direct visualization of GFP. The density of GFP-positive cells in retinal wholemounts was 1,828 +/- 299 cells/mm(2) (72,273 +/- 11,814 cells/retina). Exposure to elevated intraocular pressure was similar in all groups. Four weeks after initial laser treatment, axon loss was 52.3% +/- 27.1% in the saline-treated group (n = 25) and 52.3% +/- 24.2% in the AAV-GFP-WPRE group (n = 30), but only 32.3% +/- 23.0% in the AAV-BDNF-WPRE group (n = 27). Survival in AAV-BDNF-WPRE animals increased markedly and the difference was significant compared with those receiving either AAV-GFP-WPRE (P = 0.002, t-test) or saline (P = 0.006, t-test). Overexpression of the BDNF gene protects RGC as estimated by axon counts in a rat glaucoma model, further supporting the potential feasibility of neurotrophic therapy as a complement to the lowering of IOP in the treatment of glaucoma.

  9. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

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    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  10. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential

    Science.gov (United States)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    Objective. The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Approach. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Main results. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. Significance. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  11. Glutamatergic neurotransmission from melanopsin retinal ganglion cells is required for neonatal photoaversion but not adult pupillary light reflex.

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    Anton Delwig

    Full Text Available Melanopsin-expressing retinal ganglion cells (mRGCs in the eye play an important role in many light-activated non-image-forming functions including neonatal photoaversion and the adult pupillary light reflex (PLR. MRGCs rely on glutamate and possibly PACAP (pituitary adenylate cyclase-activating polypeptide to relay visual signals to the brain. However, the role of these neurotransmitters for individual non-image-forming responses remains poorly understood. To clarify the role of glutamatergic signaling from mRGCs in neonatal aversion to light and in adult PLR, we conditionally deleted vesicular glutamate transporter (VGLUT2 selectively from mRGCs in mice. We found that deletion of VGLUT2 in mRGCs abolished negative phototaxis and light-induced distress vocalizations in neonatal mice, underscoring a necessary role for glutamatergic signaling. In adult mice, loss of VGLUT2 in mRGCs resulted in a slow and an incomplete PLR. We conclude that glutamatergic neurotransmission from mRGCs is required for neonatal photoaversion but is complemented by another non-glutamatergic signaling mechanism for the pupillary light reflex in adult mice. We speculate that this complementary signaling might be due to PACAP neurotransmission from mRGCs.

  12. Interferon-gamma (IFN-γ-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.

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    Shahid Husain

    Full Text Available We have recently demonstrated the characterization of human tyrosinase TCR bearing h3T-A2 transgenic mouse model, which exhibits spontaneous autoimmune vitiligo and retinal dysfunction. The purpose of current study was to determine the role of T cells and IFN-γ in retina dysfunction and retinal ganglion cell (RGC death using this model. RGC function was measured by pattern electroretinograms (ERGs in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Expression of CD3, IFN-γ, GFAP, and caspases was measured by immunohistochemistry and Western blotting. All functional and structural changes were measured in 12-month-old h3T-A2 mice and compared with age-matched HLA-A2 wild-type mice. Both pattern-ERGs (42%, p = 0.03 and RGC numbers (37%, p = 0.0001 were reduced in h3T-A2 mice when compared with wild-type mice. The level of CD3 expression was increased in h3T-A2 mice (h3T-A2: 174 ± 27% vs. HLA-A2: 100%; p = 0.04. The levels of effector cytokine IFN-γ were also increased significantly in h3T-A2 mice (h3T-A2: 189 ± 11% vs. HLA-A2: 100%; p = 0.023. Both CD3 and IFN-γ immunostaining were increased in nerve fiber (NF and RGC layers of h3T-A2 mice. In addition, we have seen a robust increase in GFAP staining in h3T-A2 mice (mainly localized to NF layer, which was substantially reduced in IFN-γ ((-/- knockout h3T-A2 mice. We also have seen an up-regulation of caspase-3 and -9 in h3T-A2 mice. Based on our data we conclude that h3T-A2 transgenic mice exhibit visual defects that are mostly associated with the inner retinal layers and RGC function. This novel h3T-A2 transgenic mouse model provides opportunity to understand RGC pathology and test neuroprotective strategies to rescue RGCs.

  13. Gap junctions are essential for generating the correlated spike activity of neighboring retinal ganglion cells.

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    Béla Völgyi

    Full Text Available Neurons throughout the brain show spike activity that is temporally correlated to that expressed by their neighbors, yet the generating mechanism(s remains unclear. In the retina, ganglion cells (GCs show robust, concerted spiking that shapes the information transmitted to central targets. Here we report the synaptic circuits responsible for generating the different types of concerted spiking of GC neighbors in the mouse retina. The most precise concerted spiking was generated by reciprocal electrical coupling of GC neighbors via gap junctions, whereas indirect electrical coupling to a common cohort of amacrine cells generated the correlated activity with medium precision. In contrast, the correlated spiking with the lowest temporal precision was produced by shared synaptic inputs carrying photoreceptor noise. Overall, our results demonstrate that different synaptic circuits generate the discrete types of GC correlated activity. Moreover, our findings expand our understanding of the roles of gap junctions in the retina, showing that they are essential for generating all forms of concerted GC activity transmitted to central brain targets.

  14. Retinal nerve fiber layer and ganglion cell complex thickness assessment in patients with Alzheimer disease and mild cognitive impairment. Preliminary results

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    A. S. Tiganov

    2014-07-01

    Full Text Available Purpose: to investigate the retinal nerve fiber layer (RNFL and the macular ganglion cell complex (GCC in patients with Alzheimer`s disease and mild cognitive impairment.Methods: this study included 10 patients (20 eyes with Alzheimer`s disease, 10 patients with mild cognitive impairment and 10 age- and sex-matched healthy controls that had no history of dementia. All the subjects underwent psychiatric examination, including the Mini-Mental State Examination (MMSE, and complete ophthalmological examination, comprising optical coherence tomography and scanning laser polarimetry.Results: there was a significant decrease in GCC thickness in patients with Alzheimer`s disease compared to the control group, global loss volume of ganglion cells was higher than in control group. there was no significant difference among the groups in terms of RNFL thickness. Weak positive correlation of GCC thickness and MMSE results was observed.Conclusion: Our data confirm the retinal involvement in Alzheimer`s disease, as reflected by loss of ganglion cells. Further studies will clear up the role and contribution of dementia in pathogenesis of optic neuropathy.

  15. Long-term gene therapy causes transgene-specific changes in the morphology of regenerating retinal ganglion cells.

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    Jennifer Rodger

    Full Text Available Recombinant adeno-associated viral (rAAV vectors can be used to introduce neurotrophic genes into injured CNS neurons, promoting survival and axonal regeneration. Gene therapy holds much promise for the treatment of neurotrauma and neurodegenerative diseases; however, neurotrophic factors are known to alter dendritic architecture, and thus we set out to determine whether such transgenes also change the morphology of transduced neurons. We compared changes in dendritic morphology of regenerating adult rat retinal ganglion cells (RGCs after long-term transduction with rAAV2 encoding: (i green fluorescent protein (GFP, or (ii bi-cistronic vectors encoding GFP and ciliary neurotrophic factor (CNTF, brain-derived neurotrophic factor (BDNF or growth-associated protein-43 (GAP43. To enhance regeneration, rats received an autologous peripheral nerve graft onto the cut optic nerve of each rAAV2 injected eye. After 5-8 months, RGCs with regenerated axons were retrogradely labeled with fluorogold (FG. Live retinal wholemounts were prepared and GFP positive (transduced or GFP negative (non-transduced RGCs injected iontophoretically with 2% lucifer yellow. Dendritic morphology was analyzed using Neurolucida software. Significant changes in dendritic architecture were found, in both transduced and non-transduced populations. Multivariate analysis revealed that transgenic BDNF increased dendritic field area whereas GAP43 increased dendritic complexity. CNTF decreased complexity but only in a subset of RGCs. Sholl analysis showed changes in dendritic branching in rAAV2-BDNF-GFP and rAAV2-CNTF-GFP groups and the proportion of FG positive RGCs with aberrant morphology tripled in these groups compared to controls. RGCs in all transgene groups displayed abnormal stratification. Thus in addition to promoting cell survival and axonal regeneration, vector-mediated expression of neurotrophic factors has measurable, gene-specific effects on the morphology of injured

  16. Erythropoietin protects adult retinal ganglion cells against NMDA-, trophic factor withdrawal-, and TNF-α-induced damage.

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    Zhi-Yang Chang

    Full Text Available PURPOSE: This study aimed to evaluate the neuroprotective effect of EPO in the presence of N-methyl-d-aspartate (NMDA-, trophic factor withdrawal (TFW-, and tumor necrosis factor-alpha (TNF-α-induced toxicity on total, small, and large retinal ganglion cells (RGCs. METHODS: Retinal cells from adult rats were cultured in a medium containing brain-derived neurotrophic factor (BDNF, ciliary neurotrophic factor (CNTF, basic fibroblast growth factor (bFGF, and forskolin. Expression of RGC markers and EPOR was examined using immunocytochemistry. RGCs were classified according to their morphological properties. Cytotoxicity was induced by NMDA, TFW, or TNF-α. RGC survival was assessed by counting thy-1 and neurofilament-l double-positive cells. RESULTS: EPO offered dose-dependent (EC₅₀ = 5.7 ng/mL protection against NMDA toxicity for small RGCs; protection was not significant for large RGCs. Time-course analysis showed that the presence of EPO either before or after NMDA exposure gave effective protection. For both small and large RGCs undergoing trophic factor withdrawal, EPO at concentrations of 1, 10, or 100 ng/mL improved survival. However, EPO had to be administered soon after the onset of injury to provide effective protection. For TNF-α-induced toxicity, survival of small RGCs was seen only for the highest examined concentration (100 ng/mL of EPO, whereas large RGCs were protected at concentrations of 1, 10, or 100 ng/mL of EPO. Time-course analysis showed that pretreatment with EPO provided protection only for large RGCs; early post-treatment with EPO protected both small and large RGCs. Inhibitors of signal transduction and activators of transcription such as (STAT-5, mitogen-activated protein kinases (MAPK/extracellular-regulated kinase (ERK, and phosphatidyl inositol-3 kinase (PI3K/Akt impaired the protective effect of EPO on RGCs exposed to different insults. CONCLUSION: EPO provided neuroprotection to cultured adult rat RGCs

  17. Long-Term Gene Therapy Causes Transgene-Specific Changes in the Morphology of Regenerating Retinal Ganglion Cells

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    Rodger, Jennifer; Drummond, Eleanor S.; Hellström, Mats; Robertson, Donald; Harvey, Alan R.

    2012-01-01

    Recombinant adeno-associated viral (rAAV) vectors can be used to introduce neurotrophic genes into injured CNS neurons, promoting survival and axonal regeneration. Gene therapy holds much promise for the treatment of neurotrauma and neurodegenerative diseases; however, neurotrophic factors are known to alter dendritic architecture, and thus we set out to determine whether such transgenes also change the morphology of transduced neurons. We compared changes in dendritic morphology of regenerating adult rat retinal ganglion cells (RGCs) after long-term transduction with rAAV2 encoding: (i) green fluorescent protein (GFP), or (ii) bi-cistronic vectors encoding GFP and ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF) or growth-associated protein-43 (GAP43). To enhance regeneration, rats received an autologous peripheral nerve graft onto the cut optic nerve of each rAAV2 injected eye. After 5–8 months, RGCs with regenerated axons were retrogradely labeled with fluorogold (FG). Live retinal wholemounts were prepared and GFP positive (transduced) or GFP negative (non-transduced) RGCs injected iontophoretically with 2% lucifer yellow. Dendritic morphology was analyzed using Neurolucida software. Significant changes in dendritic architecture were found, in both transduced and non-transduced populations. Multivariate analysis revealed that transgenic BDNF increased dendritic field area whereas GAP43 increased dendritic complexity. CNTF decreased complexity but only in a subset of RGCs. Sholl analysis showed changes in dendritic branching in rAAV2-BDNF-GFP and rAAV2-CNTF-GFP groups and the proportion of FG positive RGCs with aberrant morphology tripled in these groups compared to controls. RGCs in all transgene groups displayed abnormal stratification. Thus in addition to promoting cell survival and axonal regeneration, vector-mediated expression of neurotrophic factors has measurable, gene-specific effects on the morphology of injured adult

  18. Age-dependent neuroprotection of retinal ganglion cells by tempol-C8 acyl ester in a rat NMDA toxicity model.

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    Fiedorowicz, Michal; Rejdak, Robert; Schuettauf, Frank; Wozniak, Michal; Grieb, Pawel; Thaler, Sebastian

    2014-01-01

    The efficacy of tempol and its acyl derivative tempol-C8 as retinoprotective agents was compared in a rat model of NMDA-induced retinal ganglion cell (RGC) damage. Tempol or tempol-C8 in different doses was administered intraperitoneally to 6 weeks old (pre-adolescent) and 9-10 weeks old (young adult) rats before and after an intravitreous NMDA injection. Retinal ganglion cell were retrogradely labeled with the fluorescent tracer hydroxystilbamidine and RGC counting was performed on retinal flatmounts. Intravitreal NMDA reduced RGC counts by about 90%, independently of age tempol-C8, but not tempol unmodified, showed a significant, dose-dependent RGC rescue effect, with peak activity at 5.8 µmol/kg (p tempol or tempol-C8. In contrast to tempol itself, tempol-C8 acyl ester was neuroprotective in pre-adolescent rats in the NMDA- induced RGC damage model. Therefore, neuroprotection by tempol acyl esters seems to be superior to that of tempol under certain conditions.

  19. Activated Müller Cells Involved in ATP-Induced Upregulation of P2X7 Receptor Expression and Retinal Ganglion Cell Death

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    Ying Xue

    2016-01-01

    Full Text Available P2X7 receptor (P2X7R, an ATP-gated ion channel, plays an important role in glaucomatous retinal ganglion cell (RGC apoptotic death, in which activated retinal Müller glial cells may be involved by releasing ATP. In the present study, we investigated whether and how activated Müller cells may induce changes in P2X7R expression in RGCs by using immunohistochemistry and Western blot techniques. Intravitreal injection of DHPG, a group I metabotropic glutamate receptor (mGluR I agonist, induced upregulation of GFAP expression, suggestive of Müller cell activation (gliosis, as we previously reported. Accompanying Müller cell activation, P2X7R protein expression was upregulated, especially in the cells of ganglion cell layer (GCL, which was reversed by coinjection of brilliant blue G (BBG, a P2X7R blocker. In addition, intravitreal injection of ATP also induced upregulation of P2X7R protein expression. Similar results were observed in cultured retinal neurons by ATP treatment. Moreover, both DHPG and ATP intravitreal injection induced a reduction in the number of fluorogold retrogradely labeled RGCs, and the DHPG effect was partially rescued by coinjection of BBG. All these results suggest that activated Müller cells may release ATP and, in turn, induce upregulation of P2X7R expression in the cells of GCL, thus contributing to RGC death.

  20. Network oscillations drive correlated spiking of ON and OFF ganglion cells in the rd1 mouse model of retinal degeneration.

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    David J Margolis

    Full Text Available Following photoreceptor degeneration, ON and OFF retinal ganglion cells (RGCs in the rd-1/rd-1 mouse receive rhythmic synaptic input that elicits bursts of action potentials at ∼ 10 Hz. To characterize the properties of this activity, RGCs were targeted for paired recording and morphological classification as either ON alpha, OFF alpha or non-alpha RGCs using two-photon imaging. Identified cell types exhibited rhythmic spike activity. Cross-correlation of spike trains recorded simultaneously from pairs of RGCs revealed that activity was correlated more strongly between alpha RGCs than between alpha and non-alpha cell pairs. Bursts of action potentials in alpha RGC pairs of the same type, i.e. two ON or two OFF cells, were in phase, while bursts in dissimilar alpha cell types, i.e. an ON and an OFF RGC, were 180 degrees out of phase. This result is consistent with RGC activity being driven by an input that provides correlated excitation to ON cells and inhibition to OFF cells. A2 amacrine cells were investigated as a candidate cellular mechanism and found to display 10 Hz oscillations in membrane voltage and current that persisted in the presence of antagonists of fast synaptic transmission and were eliminated by tetrodotoxin. Results support the conclusion that the rhythmic RGC activity originates in a presynaptic network of electrically coupled cells including A2s via a Na(+-channel dependent mechanism. Network activity drives out of phase oscillations in ON and OFF cone bipolar cells, entraining similar frequency fluctuations in RGC spike activity over an area of retina that migrates with changes in the spatial locus of the cellular oscillator.

  1. Network oscillations drive correlated spiking of ON and OFF ganglion cells in the rd1 mouse model of retinal degeneration.

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    Margolis, David J; Gartland, Andrew J; Singer, Joshua H; Detwiler, Peter B

    2014-01-01

    Following photoreceptor degeneration, ON and OFF retinal ganglion cells (RGCs) in the rd-1/rd-1 mouse receive rhythmic synaptic input that elicits bursts of action potentials at ∼ 10 Hz. To characterize the properties of this activity, RGCs were targeted for paired recording and morphological classification as either ON alpha, OFF alpha or non-alpha RGCs using two-photon imaging. Identified cell types exhibited rhythmic spike activity. Cross-correlation of spike trains recorded simultaneously from pairs of RGCs revealed that activity was correlated more strongly between alpha RGCs than between alpha and non-alpha cell pairs. Bursts of action potentials in alpha RGC pairs of the same type, i.e. two ON or two OFF cells, were in phase, while bursts in dissimilar alpha cell types, i.e. an ON and an OFF RGC, were 180 degrees out of phase. This result is consistent with RGC activity being driven by an input that provides correlated excitation to ON cells and inhibition to OFF cells. A2 amacrine cells were investigated as a candidate cellular mechanism and found to display 10 Hz oscillations in membrane voltage and current that persisted in the presence of antagonists of fast synaptic transmission and were eliminated by tetrodotoxin. Results support the conclusion that the rhythmic RGC activity originates in a presynaptic network of electrically coupled cells including A2s via a Na(+)-channel dependent mechanism. Network activity drives out of phase oscillations in ON and OFF cone bipolar cells, entraining similar frequency fluctuations in RGC spike activity over an area of retina that migrates with changes in the spatial locus of the cellular oscillator.

  2. Studies of Scleral Biomechanical Behavior Related to Susceptibility for Retinal Ganglion Cell Loss in Experimental Mouse Glaucoma

    Science.gov (United States)

    Nguyen, Cathy; Cone, Frances E.; Nguyen, Thao D.; Coudrillier, Baptiste; Pease, Mary E.; Steinhart, Matthew R.; Oglesby, Ericka N.; Jefferys, Joan L.; Quigley, Harry A.

    2013-01-01

    Purpose. To study anatomical changes and mechanical behavior of the sclera in mice with experimental glaucoma by comparing CD1 to B6 mice. Methods. Chronic experimental glaucoma for 6 weeks was produced in 2- to 4-month-old CD1 (43 eyes) and B6 mice (42 eyes) using polystyrene bead injection into the anterior chamber with 126 control CD1 and 128 control B6 eyes. Intraocular pressure (IOP) measurements were made with the TonoLab at baseline and after bead injection. Axial length and scleral thickness were measured after sacrifice in the CD1 and B6 animals and compared to length data from 78 eyes of DBA/2J mice. Inflation testing of posterior sclera was conducted, and circumferential and meridional strain components were determined from the displacement response. Results. Experimental glaucoma led to increases in axial length and width by comparison to fellow eyes (6% in CD1 and 10% in B6; all P glaucoma, the remainder of the sclera uniformly thinned in CD1, but thickened in B6. Peripapillary sclera in CD1 controls had significantly greater temporal meridional strain than B6 and had differences in the ratios of meridional to effective circumferential strain from B6 mice. In both CD1 and B6 mice, exposure to chronic IOP elevation resulted in stiffer pressure–strain responses for both the effective circumferential and meridional strains (multivariable regression model, P = 0.01–0.03). Conclusions. Longer eyes, greater scleral strain in some directions at baseline, and generalized scleral thinning after glaucoma were characteristic of CD1 mice that have greater tendency to retinal ganglion cell damage than B6 mice. Increased scleral stiffness after glaucoma exposure in mice mimics findings in monkey and human glaucoma eyes. PMID:23404116

  3. Retinal Ganglion Cell Protection Via Topical and Systemic Alpha-Tocopherol Administration in Optic Nerve Crush Model of Rat

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    Zeynep Aktaş

    2013-06-01

    Full Text Available Pur po se: The aim of our study was to investigate the neuroprotective effects of topical α-tocopherol in optic nerve crush model of rat and to compare its efficacy with that of systemic α -tocopherol. Ma te ri al and Met hod: 50 eyes of 25 Wistar albino rats were included. The eyes were divided into six groups. Optic nerve crush was performed in Groups 1, 3, 5. Additionally, systemic and topical α-tocopherol therapies were given to Groups 1 and 3, respectively. No treatment was applied in Group 5. Groups 2, 4, and 6 were the fellow eyes of the animals comprising Groups 1, 3, and 5. Eyes were enucleated at day 45 of the study. Retinal ganglion cells (RGCs were counted with light microscopy. Re sults: Mean RGC numbers were 14.5±3.7 (10.3-20 and 27.5±2.6 (24-30 in Groups 5 and 6, respectively (p: 0.001 They were measured to be 26.6±7.8 (19-45 and 24.6±3.9 (20-32 in Groups 1 and 2 and 21.1±7.1 (11-34 and 27±7.5 (18-42 in Groups 3 and 4 (p:0.659, p:0.094, respectively. There was no difference in Groups 2 and 4 compared with Group 6 (p:0.210, p:0.299, respectively. Dis cus si on: Topical α-tocopherol has a significant neuroprotective effects in optic nerve crush model of rat and may be used in the future for the treatment of optic neuropathies such as glaucoma. (Turk J Ophthalmol 2013; 43: 161-6

  4. GCaMP expression in retinal ganglion cells characterized using a low-cost fundus imaging system

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    Chang, Yao-Chuan; Walston, Steven T.; Chow, Robert H.; Weiland, James D.

    2017-10-01

    Objective. Virus-transduced, intracellular-calcium indicators are effective reporters of neural activity, offering the advantage of cell-specific labeling. Due to the existence of an optimal time window for the expression of calcium indicators, a suitable tool for tracking GECI expression in vivo following transduction is highly desirable. Approach. We developed a noninvasive imaging approach based on a custom-modified, low-cost fundus viewing system that allowed us to monitor and characterize in vivo bright-field and fluorescence images of the mouse retina. AAV2-CAG-GCaMP6f was injected into a mouse eye. The fundus imaging system was used to measure fluorescence at several time points post injection. At defined time points, we prepared wholemount retina mounted on a transparent multielectrode array and used calcium imaging to evaluate the responsiveness of retinal ganglion cells (RGCs) to external electrical stimulation. Main results. The noninvasive fundus imaging system clearly resolves individual (RGCs and axons. RGC fluorescence intensity and the number of observable fluorescent cells show a similar rising trend from week 1 to week 3 after viral injection, indicating a consistent increase of GCaMP6f expression. Analysis of the in vivo fluorescence intensity trend and in vitro neurophysiological responsiveness shows that the slope of intensity versus days post injection can be used to estimate the optimal time for calcium imaging of RGCs in response to external electrical stimulation. Significance. The proposed fundus imaging system enables high-resolution digital fundus imaging in the mouse eye, based on off-the-shelf components. The long-term tracking experiment with in vitro calcium imaging validation demonstrates the system can serve as a powerful tool monitoring the level of genetically-encoded calcium indicator expression, further determining the optimal time window for following experiment.

  5. Macular Ganglion Cell Inner Plexiform Layer Thickness in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects.

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    Chunwei Zhang

    Full Text Available To investigate macular ganglion cell-inner plexiform layer (mGCIPL thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL defects on stereophotographs.112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS and the African Descent and Glaucoma Evaluation Study (ADAGES subjects had standard automated perimetry (SAP, optical coherence tomography (OCT imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs.47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001 and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000. The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior mGCIPL was thinnest in the same hemiretina in 26 eyes (90%. Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001 and inferior mGCIPL (P = 0.030 compared to glaucomatous eyes without a visible RNFL defect.The current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect.

  6. Protection of neurons in the retinal ganglion cell layer against excitotoxicity by the N-acylethanolamine, N-linoleoylethanolamine

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    Duncan RS

    2011-04-01

    Full Text Available R. Scott Duncan1,*, Hua Xin1,*, Daryl L Goad1, Kent D Chapman2,3, Peter Koulen1,31Vision Research Center and Departments of Ophthalmology and Basic Medical Science, School of Medicine, University of Missouri, Kansas City, MO, USA; 2Department of Biological Sciences, University of North Texas, Denton, TX, USA; 3Center for Plant Lipid Research, University of North Texas, Denton, TX, USA *Authors contributed equallyAbstract: Retinal ganglion cell (RGC death is a hallmark of neurodegenerative diseases and disease processes of the eye, including glaucoma. The protection of RGCs has been an important strategy for combating glaucoma, but little clinical success has been reported to date. One pathophysiological consequence of glaucoma is excessive extracellular glutamate subsequently leading to excitotoxicity in the retina. Endocannabinoids, such as the N-acylethanolamine (NAE, arachidonylethanolamine (NAE 20:4, exhibit neuroprotective properties in some models of neurodegenerative disease. The majority of NAEs, however, are not cannabinoids, and their physiological function is not clear. Here, we determined whether the noncannabinoid NAE, linoleoylethanolamine (NAE18:2, protects neurons in the RGC layer against glutamate excitotoxicity in ex-vivo retina cultures. Using a terminal deoxynucleotidyl transferase-mediated dUTP (2´-deoxyuridine 5´-triphosphate nick-end labeling (TUNEL assay, we determined that NAE18:2 reduces the number of apoptotic RGC layer neurons in response to glutamate and conclude that NAE18:2 is a neuroprotective compound with potential for treating glaucomatous retinopathy.Keywords: neuroprotection, glutamate, calcium signaling, immunocytochemistry, eye, vision, glaucoma.

  7. Neuroprotective effects of tempol acyl esters against retinal ganglion cell death in a rat partial optic nerve crush model.

    Science.gov (United States)

    Thaler, Sebastian; Fiedorowicz, Michal; Grieb, Pawel; Wypych, Zbigniew; Knap, Narcyz; Borowik, Tomasz; Zawada, Katarzyna; Kaminski, Jaroslaw; Wozniak, Michal; Rejdak, Robert; Zrenner, Eberhart; Schuettauf, Frank

    2011-11-01

    The aim of this study is to search for more effective derivatives of the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl). Although tempol is neuroprotective in a rat partial optic nerve crush (PONC) model, relatively high doses are required to exert this effect. Tempol acyl esters with different-length fatty acids (tempol-C4, tempol-C8, tempol-C12 and tempol-C16) were synthesized and the following properties were evaluated: water-octanol partition coefficient, liposome-liposome energy transfer, and electron paramagnetic resonance (EPR). Brown Norway rats underwent PONC and received tempol or acyl esters intraperitoneally once daily for 7 consecutive days. We then compared the effects of tempol and its four esters on retinal ganglion cell (RGC) damage using a retrograde labelling method. The water-octanol partition coefficient increased with increasing length of attached acyl chain. However, the energy of the liposome-liposome transfer seemed to be optimal for tempol-C8 and tempol-C12. The EPR signal was very similar for all tested compounds, suggesting similar efficiency of superoxide scavenging. Partial optic nerve crush in vehicle-treated animals reduced RGC numbers by approx. 59% when compared with sham-operated eyes. Tempol did not affect RGC loss at a dose of 1 mg/kg. In contrast, at molar doses equivalent to 1 mg/kg of tempol, tempol-C8 showed a significant neuroprotective effect, whereas tempol-C4, tempol-C12 and tempol-C16 did not act neuroprotectively. Manipulating the hydrophobicity of tempol seems to be a promising tool for developing more potent neuroprotectants in the PONC degeneration model. However, the resulting compounds need further pharmacological evaluation. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

  8. Induction of Heat Shock Protein-72 by Magnetic Nanofluid Hyperthermia in Cultured Retinal Ganglion Cells for Neuroprotective Treatment in Glaucoma

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    Jin Wook Jeoung

    2015-01-01

    Full Text Available Background. Magnetic hyperthermia using superparamagnetic nanoparticle (SPNP agents is considered a promising biotechnological approach to induce heat shock proteins (HSPs in a target tissue because it can generate accurately controllable localized heating. Objectives. The main objective of this study is to demonstrate induction of HSPs in cultured retinal ganglion cells (RGCs by using engineered Mn0.5Zn0.5Fe2O4 SPNP agents coated with polyethylene glycol (PEG 500. Methods. The Mn0.5Zn0.5Fe2O4 nanoparticles were synthesized using a high temperature thermal decomposition method. The AC heating characteristics of PEG 500-coated Mn0.5Zn0.5Fe2O4 nanoparticles were investigated using an AC solenoid coil-capacitor system. Results. PEG 500-coated SPNPs efficiently penetrated into the cytoplasm of RGCs without causing obvious cytological changes and showed stable and well-saturated self-heating temperature rise characteristics. Immunofluorescent staining images showed that AC magnetic hyperthermia successfully induced HSP72 in RGCs incubated with Mn0.5Zn0.5Fe2O4 nanoparticles. In Western blot analysis, a significant increase in immunoreactivity was observed for RGCs incubated with SPNPs in a fixed AC magnetic field (fappl=140 kHz and Happl=140 Oe. Conclusion. Our results demonstrate that the induction of HSP72 with a magnetic nanofluid hyperthermia could potentially be used as a neuroprotective treatment modality by way of enhancing a natural cytoprotective response.

  9. The Photopic Negative Response: An Objective Measure of Retinal Ganglion Cell Function in Patients With Leber's Hereditary Optic Neuropathy.

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    Karanjia, Rustum; Berezovsky, Adriana; Sacai, Paula Yuri; Cavascan, Nivea Nunes; Liu, Henry Yuheng; Nazarali, Samir; Moraes-Filho, Milton Nunes; Anderson, Kirsten; Tran, Jeffrey Show; Watanabe, Sung EunSong; Moraes, Milton Nunes; Sadun, Federico; DeNegri, Anna Maria; Barboni, Piero; do Val Ferreira Ramos, Carolina; La Morgia, Chiara; Carelli, Valerio; Belfort, Rubens; Coupland, Stuart Glenn; Salomao, Solange Rios; Sadun, Alfredo A

    2017-05-01

    The photopic negative response (PhNR) is a slow negative component of a flash photopic full-field ERG that has been shown to be specific for retinal ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in patients with Leber's hereditary optic neuropathy (LHON) in which the loss of central acuity can make it difficult to monitor patients with standard metrics. The purpose of this study was to evaluate the use of PhNR as an objective noninvasive clinical metric in LHON. Full-field photopic ERG recordings were collected in subjects with the mt.11778G>A/ND4 LHON mutation using a red on blue stimulus. The PhNR was identified using a computer-based automated detection system, and data were manually examined to remove movement artifacts. The PhNR amplitude was compared between controls (n = 13), carriers (n = 17), and affected (n = 6). Mean PhNR amplitude decreased significantly across groups (P < 0.0001). Post hoc Tukey's test revealed a significant decrease in PhNR amplitude between carriers and controls (P < 0.05) and between carriers and affected (P < 0.01). We are able to demonstrate that the PhNR amplitude is significantly decreased in patients affected by LHON compared to carriers in a well-described pedigree. Surprisingly, there was also a decrease in PhNR in carriers, suggesting potential subclinical RGC dysfunction in some carriers. This is important in patients affected with LHON who typically have a dense central scotoma. The PhNR may be a useful objective outcome measure for future clinical trials.

  10. Transgenic inhibition of astroglial NF-κB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis

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    Brambilla Roberta

    2012-09-01

    Full Text Available Abstract Background Optic neuritis is an acute, demyelinating neuropathy of the optic nerve often representing the first appreciable symptom of multiple sclerosis. Wallerian degeneration of irreversibly damaged optic nerve axons leads to death of retinal ganglion cells, which is the cause of permanent visual impairment. Although the specific mechanisms responsible for triggering these events are unknown, it has been suggested that a key pathological factor is the activation of immune-inflammatory processes secondary to leukocyte infiltration. However, to date, there is no conclusive evidence to support such a causal role for infiltrating peripheral immune cells in the etiopathology of optic neuritis. Methods To dissect the contribution of the peripheral immune-inflammatory response versus the CNS-specific inflammatory response in the development of optic neuritis, we analyzed optic nerve and retinal ganglion cells pathology in wild-type and GFAP-IκBα-dn transgenic mice, where NF-κB is selectively inactivated in astrocytes, following induction of EAE. Results We found that, in wild-type mice, axonal demyelination in the optic nerve occurred as early as 8 days post induction of EAE, prior to the earliest signs of leukocyte infiltration (20 days post induction. On the contrary, GFAP-IκBα-dn mice were significantly protected and showed a nearly complete prevention of axonal demyelination, as well as a drastic attenuation in retinal ganglion cell death. This correlated with a decrease in the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, as well as a prevention of NAD(PH oxidase subunit upregulation. Conclusions Our results provide evidence that astrocytes, not infiltrating immune cells, play a key role in the development of optic neuritis and that astrocyte-mediated neurotoxicity is dependent on activation of a transcriptional program regulated by NF-κB. Hence, interventions targeting the NF-κB transcription

  11. Effect of lycium barbarum polysaccharides on high glucose-induced retinal ganglion cell apoptosis, gene expression and delayed rectifier potassium current

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    Xiao-Fei Ma

    2017-05-01

    Full Text Available Objective: To study the effect of lycium barbarum polysaccharides (LBP on high glucoseinduced retinal ganglion cell apoptosis, gene expression and delayed rectifier potassium current. Methods: RGC-5 retinal ganglion cell lines were cultured and divided into control group, high glucose group and LBP group that were treated with normal DMEM, highglucose DMEM as well as high-glucose DMEM containing 500 ng/mL LBP respectively. After treatment, the Annexin V-FITC/PI kits were used to measure the number of apoptotic cells, fluorescence quantitative PCR kits were used to determine the expression of apoptosis genes and antioxidant genes, and patch clamp was used to test delayed rectifier potassium current. Results: 12, 24, 36 and 48 h after intervention, the number of apoptotic cells of high glucose group was significantly higher than that of control group, and the number of apoptotic cells of LBP group was significantly lower than that of high glucose group (P<0.05; 24 and 48 h after intervention, c-fos, c-jun, caspase-3, caspase-9, Nrf-2, NQO1 and HO-1 mRNA expression as well as potassium current amplitude (IK and maximum conductance (Gmax of high glucose group were significantly higher than those of control group while half maximum activation voltage (V1/2 was significantly lower than that of control group (P<0.05; c-fos, c-jun, caspase-3 and caspase-9 mRNA expression as well as IK and Gmax of LBP group were significantly lower than those of high glucose group, while Nrf-2, NQO1 and HO-1 mRNA expression as well as V1/2 of LBP group were significantly higher than those of high glucose group (P<0.05. Conclusions: LBP can reduce the high glucose-induced retinal ganglion cell apoptosis and inhibit the delayed rectifier potassium current amplitude.

  12. [The neuroprotective effect of erigeron breviscapus (vant) hand-mazz on retinal ganglion cells after optic nerve crush injury].

    Science.gov (United States)

    Jiang, Bing; Jiang, You-qin

    2003-08-01

    To investigate whether a Chinese herbal medicine, erigeron breviscapus (vant) hand-mazz (EBHM), can protect the retinal ganglion cells (RGC) damaged by calibrated optic nerve crush injury. Forty-two Sprague-Dawley rats were randomly divided into two groups. Calibrated optic nerve crush injury model was induced in the right eyes by a special designed optic nerve clip. The left eyes served as a control. All 42 rats were randomly divided into 2 groups. Group A consisted of the rats with calibrated optic nerve crush injury and group B consisted of rats with calibrated optic nerve crush injury treated with EBHM. In group B, EBHM solution was given once after the crush injury. According to the time interval between the optic nerve crush and the sacrifice, both groups A and B were further divided into three subgroups (day 4, day 14 and day 21). Therefore, there were 7 rats in each subgroup. Three days before sacrifice, 3% fast blue was injected into superior colliculi bilaterally. The eyes were enucleated after the rat was sacrificed, and flat mounts of the retina from both eyes were prepared on a slide and observed under a fluorescence microscope. Four photos with 400 x magnification were taken from each of the four quadrants of the retina 1 mm away from the optic disc. The labeled RGC were counted by a computerized image analyzer. The labeled RGC rate was used for statistical analysis (the labeled RGC rate = number of RGC in injured eye/control eye x 100%). In group A, the labeled RGC rate was (77.79 +/- 7.11)%, (63.76 +/- 3.79)% and (54.66 +/- 4.75)% on day 4, day 14 and day 21, respectively. In group B, the labeled RGC rate was (80.13 +/- 12.03)%, (78.17 +/- 9.19)% and (83.59 +/- 12.61)% on day 4, day 14 and day 21, respectively. In group B, which was treated with EBHM after injury, the labeled RGC rate was significantly higher than that of group A on day 14 and day 21. In the experimental optic nerve crush model in rats, EBHM therapy can increase the survival rate of

  13. Characterization of intravitreally delivered capsid mutant AAV2-Cre vector to induce tissue-specific mutations in murine retinal ganglion cells.

    Science.gov (United States)

    Langouet-Astrie, Christophe J; Yang, Zhiyong; Polisetti, Sraavya M; Welsbie, Derek S; Hauswirth, William W; Zack, Donald J; Merbs, Shannath L; Enke, Raymond A

    2016-10-01

    Targeted expression of Cre recombinase in murine retinal ganglion cells (RGCs) by viral vector is an effective strategy for creating tissue-specific gene knockouts for investigation of genetic contribution to RGC degeneration associated with optic neuropathies. Here we characterize dosage, efficacy and toxicity for sufficient intravitreal delivery of a capsid mutant Adeno-associated virus 2 (AAV2) vector encoding Cre recombinase. Wild type and Rosa26 (R26) LacZ mice were intravitreally injected with capsid mutant AAV2 viral vectors. Murine eyes were harvested at intervals ranging from 2 weeks to 15 weeks post-injection and were assayed for viral transduction, transgene expression and RGC survival. 10(9) vector genomes (vg) were sufficient for effective in vivo targeting of murine ganglion cell layer (GCL) retinal neurons. Transgene expression was observed as early as 2 weeks post-injection of viral vectors and persisted to 11 weeks. Early expression of Cre had no significant effect on RGC survival, while significant RGC loss was detected beginning 5 weeks post-injection. Early expression of viral Cre recombinase was robust, well-tolerated and predominantly found in GCL neurons suggesting this strategy can be effective in short-term RGC-specific mutation studies in experimental glaucoma models such as optic nerve crush and transection experiments. RGC degeneration with Cre expression for more than 4 weeks suggests that Cre toxicity is a limiting factor for targeted mutation strategies in RGCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Both systemic and local application of Granulocyte-colony stimulating factor (G-CSF is neuroprotective after retinal ganglion cell axotomy

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    Dietz Gunnar PH

    2009-05-01

    Full Text Available Abstract Background The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC axotomy model to compare effects of local and systemic application of neuroprotective molecules. Results We found that the G-CSF receptor is robustly expressed by RGCs in vivo and in vitro. We thus evaluated G-CSF as a neuroprotectant for RGCs and found a dose-dependent neuroprotective effect of G-CSF on axotomized RGCs when given subcutaneously. As stem stell mobilization had previously been discussed as a possible contributor to the neuroprotective effects of G-CSF, we compared the local treatment of RGCs by injection of G-CSF into the vitreous body with systemic delivery by subcutaneous application. Both routes of application reduced retinal ganglion cell death to a comparable extent. Moreover, G-CSF enhanced the survival of immunopurified RGCs in vitro. Conclusion We thus show that G-CSF neuroprotection is at least partially independent of potential systemic effects and provide further evidence that the clinically applicable G-CSF could become a treatment option for both neurodegenerative diseases and glaucoma.

  15. The dark phase intraocular pressure elevation and retinal ganglion cell degeneration in a rat model of experimental glaucoma☆

    Science.gov (United States)

    Kwong, Jacky M.K.; Vo, Nancy; Quan, Ann; Nam, Michael; Kyung, Haksu; Yu, Fei; Piri, Natik; Caprioli, Joseph

    2013-01-01

    Intraocular pressure (IOP) elevation is considered as a major risk factor causing the progression of vision deterioration in glaucoma. Although it is known that the IOP level changes widely throughout the day and night, how the dark or light phase IOP elevation contributes to retinal ganglion cell (RGC) degeneration is still largely unclear. To examine the profile of IOP, modified laser photocoagulation was applied to the trabecular meshwork of Brown Norway rats and both light and dark phase IOPs were monitored approximately 1–2 times a week. The relationship between IOP elevation and RGC degeneration was investigated while RGC body loss was analyzed with Rbpms immunolabeling on retinal wholemount and axonal injury in the optic nerve was semi-quantified. The baseline awake dark and light IOPs were 30.4 ± 2.7 and 20.2 ± 2.1 mmHg respectively. The average dark IOP was increased to 38.2 ± 3.2 mmHg for five weeks after the laser treatment on 270° trabecular meshwork. However, there was no significant loss of RGC body and axonal injury. After laser treatment on 330° trabecular meshwork, the dark and light IOPs were significantly increased to 43.8 ± 4.6 and 23 ± 3.7 mmHg respectively for 5 weeks. The cumulative dark and light IOP elevations were 277 ± 86 and 113 ± 50 mmHg days respectively while the cumulative total (light and dark) IOP elevation was 213 ± 114 mmHg days. After 5 weeks, regional RGC body loss of 29.5 ± 15.5% and moderate axonal injury were observed. Axonal injury and loss of RGC body had a high correlation with the cumulative total IOP elevation (R2 = 0.60 and 0.65 respectively). There was an association between the cumulative dark IOP elevation and RGC body loss (R2 = 0.37) and axonal injury (R2 = 0.51) whereas the associations between neuronal damages and the cumulative light IOP elevation were weak (for RGC body loss, R2 = 0.01; for axonal injury, R2 = 0.26). Simple linear regression model analysis showed statistical significance for the

  16. Selective A2A receptor antagonist prevents microglia-mediated neuroinflammation and protects retinal ganglion cells from high intraocular pressure-induced transient ischemic injury.

    Science.gov (United States)

    Madeira, Maria H; Boia, Raquel; Elvas, Filipe; Martins, Tiago; Cunha, Rodrigo A; Ambrósio, António Francisco; Santiago, Ana Raquel

    2016-03-01

    Glaucoma is a leading cause of vision loss and blindness worldwide, characterized by chronic and progressive neuronal loss. Reactive microglial cells have been recognized as a neuropathologic feature, contributing to local inflammation and retinal neurodegeneration. In a recent in vitro work (organotypic cultures), we demonstrated that blockade of adenosine A2A receptor (A2AR) prevents the neuroinflammatory response and affords protection to retinal ganglion cells (RGCs) against exposure to elevated hydrostatic pressure (EHP), to mimic elevated intraocular pressure (IOP), the main risk factor for glaucoma development. Herein, we investigated whether a selective A2AR antagonist (SCH 58261) could modulate retinal microglia reactivity and their inflammatory response. Furthermore, we took advantage of the high IOP-induced transient ischemia (ischemia-reperfusion, I-R) animal model to evaluate the protective role of A2AR blockade in the control of retinal neuroinflammation and neurodegeneration. Primary microglial cell cultures were challenged either with lipopolysaccharide or with EHP, in the presence or absence of A2AR antagonist SCH 58261 (50 nM). In addition, I-R injury was induced in adult Wistar rats after intravitreal administration of SCH 58261 (100 nM, 5 μL). Our results showed that SCH 58261 attenuated microglia reactivity and the increased expression and release of proinflammatory cytokines. Moreover, intravitreal administration of SCH 58261 prevented I-R-induced cell death and RGC loss, by controlling microglial-mediated neuroinflammatory response. These results prompt the proposal that A2AR blockade may have great potential in the management of retinal neurodegenerative diseases characterized by microglia reactivity and RGC death, such as glaucoma and ischemic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. RNAi targeting Nogo Receptor enhanced survival and proliferation of murine retinal ganglion cells during N-methyl-D-aspartate-induced optic nerve crush.

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    Zeng, Kun; Zhong, Bo; Shen, Xiao-Li; Fang, Min; Lin, Bao-Tao; Ma, Da-Hui

    2017-09-12

    We investigated the effects of lentivirus-mediated RNAi targeting of Nogo Receptor ( NgR ) on the proliferation and survival of murine retinal ganglion cells (mRGCs) in vitro and in vivo . Cultured mRGCs and C57BL/6 male mice were divided into 4 experimental groups: blank, model [100 μM N-methyl-D-aspartate (NMDA)], nscRNA (100 μM NMDA+ nscRNA vectors) and siNgR (100 μM NMDA+ siNgR vectors). CCK-8 and flow cytometry analyses revealed that silencing NgR enhanced proliferation, cell cycling and survival of NMDA-treated mRGCs. H&E staining showed that NgR silencing enhanced mRGC cell density and reduced angiogenesis in NMDA-treated retinal tissues. TUNEL assays showed that mRGC apoptosis was significantly diminished by NgR silencing in NMDA-treated retinal tissues. Western blotting and qRT-PCR analysis in NMDA-treated mRGCs and murine retinal tissues revealed that NgR silencing resulted in downregulation of RhoA signaling (RhoA and ROCK2). Western blotting showed that levels of activated Bax and cleaved caspase 3 were decreased, while Bcl-2 and pro-caspase 3 were increased in NMDA-treated mRGCs and murine retinal tissues, which corroborated the decreased apoptosis. These findings indicate that NgR gene silencing increases proliferation and survival of mRGCs in NMDA-treated murine retinas, which suggests a potential for therapeutic application to preventing optic nerve damage.

  18. Activation of ganglion cells and axon bundles using epiretinal electrical stimulation.

    Science.gov (United States)

    Grosberg, Lauren E; Ganesan, Karthik; Goetz, Georges A; Madugula, Sasidhar S; Bhaskhar, Nandita; Fan, Victoria; Li, Peter; Hottowy, Pawel; Dabrowski, Wladyslaw; Sher, Alexander; Litke, Alan M; Mitra, Subhasish; Chichilnisky, E J

    2017-09-01

    Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single

  19. Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor.

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    Leibinger, Marco; Müller, Adrienne; Andreadaki, Anastasia; Hauk, Thomas G; Kirsch, Matthias; Fischer, Dietmar

    2009-11-11

    After optic nerve injury retinal ganglion cells (RGCs) normally fail to regenerate axons in the optic nerve and undergo apoptosis. However, lens injury (LI) or intravitreal application of zymosan switch RGCs into an active regenerative state, enabling these neurons to survive axotomy and to regenerate axons into the injured optic nerve. Several factors have been proposed to mediate the beneficial effects of LI. Here, we investigated the contribution of glial-derived ciliary neurotrophic factor (CNTF) to LI-mediated regeneration and neuroprotection using wild-type and CNTF-deficient mice. In wild-type mice, CNTF expression was strongly upregulated in retinal astrocytes, the JAK/STAT3 pathway was activated in RGCs, and RGCs were transformed into an active regenerative state after LI. Interestingly, retinal LIF expression was correlated with CNTF expression after LI. In CNTF-deficient mice, the neuroprotective and axon growth-promoting effects of LI were significantly reduced compared with wild-type animals, despite an observed compensatory upregulation of LIF expression in CNTF-deficient mice. The positive effects of LI and also zymosan were completely abolished in CNTF/LIF double knock-out mice, whereas LI-induced glial and macrophage activation was not compromised. In culture CNTF and LIF markedly stimulated neurite outgrowth of mature RGCs. These data confirm a key role for CNTF in directly mediating the neuroprotective and axon regenerative effects of inflammatory stimulation in the eye and identify LIF as an additional contributing factor.

  20. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells.

    Science.gov (United States)

    Mesentier-Louro, Louise A; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

    2017-01-05

    Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75 NTR , TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75 NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75 NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  1. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells

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    Louise A. Mesentier-Louro

    2017-01-01

    Full Text Available Nerve growth factor (NGF is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC degenerate following optic-nerve crush (ONC, even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  2. Bioactive compounds in green tea leaves attenuate the injury of retinal ganglion RGC-5 cells induced by H2O2 and ultraviolet radiation.

    Science.gov (United States)

    Jin, Jianchang; Ying, Hao; Huang, Meirong; Du, Qizhen

    2015-11-01

    The Chinese commonly believe that tea helps maintain clear vision. This viewpoint has been recorded in Chinese medical books also. The key bioactive compounds in green tea leaves, (-)-epigallocatechin gallate (EGCG), L-theanine (theanine) and caffeine, were investigated for their abilities to attenuate the injury of retinal ganglion cells (RGC-5) induced by H2O2 and ultraviolet radiation. Theanine and caffeine promoted cell growth while concentrations of EGCG greater than 10μg/ml inhibited cell growth. The nine and caffeine both protected RGC-5 cells from injury as well as enhanced their recovery, while EGCG only protected the cells from injury and did not help them to recover. Tea is a unique drink, which is simultaneously enriched with EGCG, theanine and caffeine. The role of these compounds in optic nerve protection may partially explain why some tea drinkers feel enhanced vision.

  3. Vesicular glutamate transporter 2 (VGLUT2) is co-stored with PACAP in projections from the rat melanopsin-containing retinal ganglion cells

    DEFF Research Database (Denmark)

    Engelund, Anna Iversen; Fahrenkrug, Jan; Harrison, Adrian Paul

    2010-01-01

    transcardially perfusion-fixated, after which the brains and eyes were removed for double immunohistochemical staining using a polyclonal anti-VGLUT2 antibody and a mouse monoclonal anti-PACAP antibody. Results revealed that VGLUT2- and PACAP-immunoreactivity (-ir) were present in ipRGCs and co......The retinal ganglion cell layer of the eye comprises a subtype of cells characterized by their intrinsic photosensitivity and expression of melanopsin (ipRGCs). These cells regulate a variety of non-image-forming (NIF) functions such as light entrainment of circadian rhythms, acute suppression......-localization of vesicular glutamate transporter 2 (VGLUT2; a marker of glutamate signaling) and PACAP in ipRGCs and their projections in the brain. Nine adult male Wistar rats were assigned to one of three groups; anterograde tracing (n = 3), eye enucleation (n = 3), and untreated (n = 3). Under anaesthesia, rats were...

  4. Effects of early postnatal exposure to ethanol on retinal ganglion cell morphology and numbers of neurons in the dorsolateral geniculate in mice

    Science.gov (United States)

    Dursun, Ilknur; Jakubowska-Doğru, Ewa; van der List, Deborah; Liets, Lauren C.; Coombs, Julie L.; Berman, Robert F.

    2012-01-01

    Background The adverse effects of fetal and early postnatal ethanol intoxication on peripheral organs and the central nervous system are well documented. Ocular defects have also been reported in about 90% of children with Fetal Alcohol Syndrome (FAS), including microphthalmia, loss of neurons in the retinal ganglion cell layer (GCL), optic nerve hypoplasia and dysmyelination. However, little is known about perinatal ethanol effects on retinal cell morphology. Examination of the potential toxic effects of alcohol on the neuron architecture is important since the changes in dendritic geometry and synapse distribution directly affect the organization and functions of neural circuits. Thus, in the present study estimations of the numbers of neurons in the GCL and dorsolateral geniculate nucleus (dLGN), and a detailed analysis of RGC morphology were carried out in transgenic mice exposed to ethanol during the early postnatal period. Methods The study was carried out in male and female transgenic mice expressing Yellow Fluorescent Protein (YFP) controlled by a Thy-1 (thymus cell antigen 1) regulator on a C57 background. Ethanol (3 g/kg/day) was administered to mouse pups by intragastric intubation throughout postnatal days (PD) 3–20. Intubation control (IC) and untreated control (C) groups were included. Blood alcohol concentration (BAC) was measured in separate groups of pups on PD3, PD10, and PD20 at 4 different time points, 1, 1.5, 2 and 3 h after the second intubation. Numbers of neurons in the GCL and in the dLGN were quantified on PD20 using unbiased stereological procedures. Retinal ganglion cell morphology was imaged by confocal microscopy and analyzed using Neurolucida software. Results Binge-like ethanol exposure in mice during the early postnatal period from PD3 through PD20 altered RGC morphology and resulted in a significant decrease in the numbers of neurons in the GCL and in the dLGN. In the alcohol exposure group, out of 13 morphological parameters

  5. Variations of retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer thickness according to the torsion direction of optic disc.

    Science.gov (United States)

    Lee, Kang Hoon; Kim, Chan Yun; Kim, Na Rae

    2014-02-20

    To examine the relationship between the optic disc torsion and peripapillary retinal nerve fiber layer (RNFL) thickness through a comparison with the macular ganglion cell inner plexiform layer complex (GCIPL) thickness measured by Cirrus optical coherence tomography (OCT). Ninety-four eyes of 94 subjects with optic disc torsion and 114 eyes of 114 subjects without optic disc torsion were enrolled prospectively. The participants underwent fundus photography and OCT imaging in peripapillary RNFL mode and macular GCIPL mode. The participants were divided into groups according to the presence or absence of optic disc torsion. The eyes with optic disc torsion were further divided into supranasal torsion and inferotemporal torsion groups according to the direction of optic disc torsion. The mean RNFL and GCIPL thicknesses for the quadrants and subsectors were compared. The superior and inferior peak locations of the RNFL were also measured according to the torsion direction. The temporal RNFL thickness was significantly thicker in inferotemporal torsion, whereas the GCIPL thickness at all segments was unaffected. The inferotemporal optic torsion had more temporally positioned superior peak locations of the RNFL than the nontorsion and supranasal-torted optic disc. Thickening of the temporal RNFL with a temporal shift in the superior peak within the eyes with inferotemporal optic disc torsion can lead to interpretation errors. The ganglion cell analysis algorithm can assist in differentiating eyes with optic disc torsion.

  6. Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early developmental stages of human retinal ganglion cells in embryonic stem cell derived retina.

    Science.gov (United States)

    Aparicio, J G; Hopp, H; Choi, A; Mandayam Comar, J; Liao, V C; Harutyunyan, N; Lee, T C

    2017-01-01

    Human retinal ganglion cells (RGCs) derived from pluripotent stem cells (PSCs) have anticipated value for human disease study, drug screening, and therapeutic applications; however, their full potential remains underdeveloped. To characterize RGCs in human embryonic stem cell (hESC) derived retinal organoids we examined RGC markers and surface antigen expression and made comparisons to human fetal retina. RGCs in both tissues exhibited CD184 and CD171 expression and distinct expression patterns of the RGC markers BRN3 and RBPMS. The retinal progenitor cells (RPCs) of retinal organoids expressed CD184, consistent with its expression in the neuroblastic layer in fetal retina. In retinal organoids CD184 expression was enhanced in RGC competent RPCs and high CD184 expression was retained on post-mitotic RGC precursors; CD171 was detected on maturing RGCs. The differential expression timing of CD184 and CD171 permits identification and enrichment of RGCs from retinal organoids at differing maturation states from committed progenitors to differentiating neurons. These observations will facilitate molecular characterization of PSC-derived RGCs during differentiation, critical knowledge for establishing the veracity of these in vitro produced cells. Furthermore, observations made in the retinal organoid model closely parallel those in human fetal retina further validating use of retinal organoid to model early retinal development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss of retinal ganglion cells in mice.

    Science.gov (United States)

    Kashiwagi, Kenji; Ito, Sadahiro; Maeda, Shuichiro; Kato, Goro

    2017-12-01

    Src knockout mice show no detectable abnormalities in central nervous system (CNS) post-mitotic neurons, likely reflecting functional compensation by other Src family kinases. Cdk1- or Cdk5-dependent Ser75 phosphorylation in the amino-terminal Unique domain of Src, which shares no homology with other Src family kinases, regulates the stability of active Src. To clarify the roles of Src Ser75 phosphorylation in CNS neurons, we established two types of mutant mice with mutations in Src: phospho-mimicking Ser75Asp (SD) and non-phosphorylatable Ser75Ala (SA). In ageing SD/SD mice, retinal ganglion cell (RGC) number in whole retinas was significantly lower than that in young SD/SD mice in the absence of inflammation and elevated intraocular pressure, resembling the pathogenesis of progressive optic neuropathy. By contrast, SA/SA mice and wild-type (WT) mice exhibited no age-related RGC loss. The age-related retinal RGC number reduction was greater in the peripheral rather than the mid-peripheral region of the retina in SD/SD mice. Furthermore, Rho-associated kinase activity in whole retinas of ageing SD/SD mice was significantly higher than that in young SD/SD mice. These results suggest that Src regulates RGC survival during ageing in a manner that depends on Ser75 phosphorylation.

  8. The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.

    Science.gov (United States)

    Kobayashi, Mamoru; Hirooka, Kazuyuki; Ono, Aoi; Nakano, Yuki; Nishiyama, Akira; Tsujikawa, Akitaka

    2017-03-01

    Excitotoxicity, which is due to glutamate-induced toxic effects on the retinal ganglion cell (RGC), is one of several mechanisms of RGC loss. The renin-angiotensin-aldosterone system (RAAS) has also been implicated in RGC death. Therefore, it is important to determine the exact relationship between the RAAS and N-methyl-d-aspartate (NMDA) receptor-mediated signal in order to prevent RGC death. N-methyl-d-aspartate or aldosterone was injected into the vitreous body. After intravitreal injection of NMDA or aldosterone, animals were treated with spironolactone or memantine. Retinal damage was evaluated by measuring the number of RGCs at 4 weeks after local administration of aldosterone or at 2 weeks after local administration of NMDA. Vitreous humor levels of aldosterone were measured using enzyme immunoassay kits. A significantly decreased number of RGCs were observed after intravitreal injection of NMDA. Although spironolactone did not show any neuroprotective effects, memantine significantly reduced NMDA-induced degeneration in the retina. Furthermore, a significant decrease in the number of RGCs was observed after an intravitreal injection of aldosterone. While memantine did not exhibit any neuroprotective effects, spironolactone caused a significant reduction in the aldosterone-induced degeneration in the retina. There was no change in the aldosterone concentration in the vitreous humor after an NMDA injection. Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.

  9. Differentiation of retinal ganglion cells and photoreceptor precursors from mouse induced pluripotent stem cells carrying an Atoh7/Math5 lineage reporter.

    Directory of Open Access Journals (Sweden)

    Bin-Bin Xie

    Full Text Available The neural retina is a critical component of the visual system, which provides the majority of sensory input in humans. Various retinal degenerative diseases can result in the permanent loss of retinal neurons, especially the light-sensing photoreceptors and the centrally projecting retinal ganglion cells (RGCs. The replenishment of lost RGCs and the repair of optic nerve damage are particularly challenging, as both RGC specification and their subsequent axonal growth and projection involve complex and precise regulation. To explore the developmental potential of pluripotent stem cell-derived neural progenitors, we have established mouse iPS cells that allow cell lineage tracing of progenitors that have expressed Atoh7/Math5, a bHLH transcription factor required for RGC production. These Atoh7 lineage reporter iPS cells encode Cre to replace one copy of the endogenous Atoh7 gene and a Cre-dependent YFP reporter in the ROSA locus. In addition, they express pluripotent markers and are capable of generating teratomas in vivo. Under anterior neural induction and neurogenic conditions in vitro, the Atoh7-Cre/ROSA-YFP iPS cells differentiate into neurons that co-express various RGC markers and YFP, indicating that these neurons are derived from Atoh7-expressing progenitors. Consistent with previous in vivo cell lineage studies, the Atoh7-Cre/ROSA-YFP iPS cells also give rise to a subset of Crx-positive photoreceptor precursors. Furthermore, inhibition of Notch signaling in the iPSC cultures results in a significant increase of YFP-positive RGCs and photoreceptor precursors. Together, these results show that Atoh7-Cre/ROSA-YFP iPS cells can be used to monitor the development and survival of RGCs and photoreceptors from pluripotent stem cells.

  10. Correlation between macular ganglion cell-inner plexiform layer thickness and visual acuity after resolution of the macular edema secondary to central retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Hyun Ju Kim

    2018-02-01

    Full Text Available AIM: To examine the thickness of the ganglion cell-inner plexiform layer (GCIPL in eyes with resolved macular edema (ME in non-ischemic central retinal vein occlusion (CRVO, applying spectral-domain optical coherence tomography (SD-OCT, and its relationship with visual acuity. METHODS: The retrospective observational case-control study included 30 eyes of non-ischemic CRVO patients with resolved ME (ME eyes after treatment, and 30 eyes of non-ischemic CRVO patients without ME (non-ME eyes. The macular GCIPL thickness, peripapillary retinal nerve fiber layer (pRNFL thickness and central macular thickness (CMT were measured on a SD-OCT scan. Linear regression analyses were performed to determine the correlation between the thickness of each and the visual acuity (VA. RESULTS: No significant difference in average GCIPL thickness, mean pRNFL thickness and CMT were observed between ME group and non-ME group (P=0.296, 0.183, 0.846. But, minimum GCIPL thickness was reduced in ME eyes compared with non-ME eyes (P=0.022. Final VA significantly correlated with the minimum GCIPL thickness in ME eyes (r=-0.482, P=0.007, whereas no correlation was found with average GCIPL thickness, average pRNFL thickness and mean CMT. CONCLUSION: Minimum GCIPL thickness is reduced in ME eyes compared with non-ME eyes, and correlated with the VA in non-ischemic CRVO. These results propose that inner retinal damage occurring in patients with ME secondary to non-ischemic CRVO may lead to permanent visual defect after treatment.

  11. Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia

    DEFF Research Database (Denmark)

    Kyhn, Maria Voss; Klassen, Henry; Johansson, Ulrica Englund

    2009-01-01

    This study investigates whether intravitreal administration of glial cell line-derived neurotrophic factor (GDNF) enhances survival of NeuN positive retinal cells in a porcine model of retinal ischemia. 16 pigs were subjected to an ischemic insult where intraocular pressure was maintained at 5 mm...... electroretinography (mfERG), quantification of NeuN positive cells and evaluation of the degree of retinal perivasculitis and inflammation 6 weeks after the insult. In the post-injection eyes (days 14, 28 and 42), the ratios of the iN1 and the iP2 amplitudes were 0.10 (95% CI: 0.05-0.15) and 0.09 (95% CI: 0.......04-0.16) in eyes treated with blank microspheres, and 0.24 (95% CI: 0.18-0.32) and 0.23 (95% CI: 0.15-0.33) in eyes treated with GDNF microspheres. These differences were statistically significant (P eyes...

  12. AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells

    NARCIS (Netherlands)

    Leaver, Simone G; Cui, Qi; Plant, Giles W; Arulpragasam, A.; Hisheh, S; Verhaagen, J; Harvey, Alan R

    We compared the effects of intravitreal injection of bi-cistronic adeno-associated viral (AAV-2) vectors encoding enhanced green fluorescent protein (GFP) and either ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF) or growth-associated protein-43 (GAP43) on adult retinal

  13. In vivowide-field multispectral scanning laser ophthalmoscopy-optical coherence tomography mouse retinal imager: longitudinal imaging of ganglion cells, microglia, and Müller glia, and mapping of the mouse retinal and choroidal vasculature

    Science.gov (United States)

    Zhang, Pengfei; Zam, Azhar; Jian, Yifan; Wang, Xinlei; Li, Yuanpei; Lam, Kit S.; Burns, Marie E.; Sarunic, Marinko V.; Pugh, Edward N., Jr.; Zawadzki, Robert J.

    2015-12-01

    Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) provide complementary views of the retina, with the former collecting fluorescence data with good lateral but relatively low-axial resolution, and the latter collecting label-free backscattering data with comparable lateral but much higher axial resolution. To take maximal advantage of the information of both modalities in mouse retinal imaging, we have constructed a compact, four-channel, wide-field (˜50 deg) system that simultaneously acquires and automatically coregisters three channels of confocal SLO and Fourier domain OCT data. The scanner control system allows "zoomed" imaging of a region of interest identified in a wide-field image, providing efficient digital sampling and localization of cellular resolution features in longitudinal imaging of individual mice. The SLO is equipped with a "flip-in" spectrometer that enables spectral "fingerprinting" of fluorochromes. Segmentation of retina layers and en face display facilitate spatial comparison of OCT data with SLO fluorescence patterns. We demonstrate that the system can be used to image an individual retinal ganglion cell over many months, to simultaneously image microglia and Müller glia expressing different fluorochromes, to characterize the distinctive spatial distributions and clearance times of circulating fluorochromes with different molecular sizes, and to produce unequivocal images of the heretofore uncharacterized mouse choroidal vasculature.

  14. Comparing the Rates of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Loss in Healthy Eyes and in Glaucoma Eyes.

    Science.gov (United States)

    Hammel, Naama; Belghith, Akram; Weinreb, Robert N; Medeiros, Felipe A; Mendoza, Nadia; Zangwill, Linda M

    2017-06-01

    To compare the rates of circumpapillary retinal nerve fiber layer (RNFL) and macular retinal ganglion cell-inner plexiform layer (GCIPL) change over time in healthy and glaucoma eyes. Cohort study. The rates of circumpapillary RNFL and macular GCIPL loss in 28 healthy subjects and 97 glaucoma subjects from the Diagnostic Innovations in Glaucoma Study (DIGS) were compared using mixed-effects models. The median follow-up time and number of visits were 1.7 years and 6 visits and 3.2 years and 7 visits for healthy and glaucoma eyes, respectively. Significant rates of loss of both global circumpapillary RNFL and average macular GCIPL thickness were detectable in early and moderate glaucoma eyes; in severe glaucoma eyes, rates of average macular GCIPL loss were significant, but rates of global circumpapillary RNFL loss were not. In glaucoma eyes, mean rates of global circumpapillary RNFL thickness change (-0.98 μm/year [95% confidence interval (CI), -1.20 to -0.76]) and normalized global circumpapillary RNFL change (-1.7%/year [95% CI, -2.1 to -1.3]) were significantly faster than average macular GCIPL change (-0.57 μm/year [(95% CI, -0.73 to -0.41]) and normalized macular GCIPL change (-1.3%/year [95% CI, -1.7 to -0.9]). The rates of global and inferior RNFL change were weakly correlated with global and inferior macular GCIPL change (r ranges from 0.16 to 0.23, all P glaucoma eyes. Global circumpapillary RNFL thickness loss was detectable in early and moderate glaucoma, and average macular GCIPL thickness loss was detectable in early, moderate, and severe glaucoma, suggesting that structural changes can be detected in severe glaucoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Thickness of the Macula, Retinal Nerve Fiber Layer, and Ganglion Cell Layer in the Epiretinal Membrane: The Repeatability Study of Optical Coherence Tomography.

    Science.gov (United States)

    Lee, Haeng-Jin; Kim, Min-Su; Jo, Young-Joon; Kim, Jung-Yeul

    2015-07-01

    To analyze the repeatability of measurements of the thicknesses of the macula, retinal nerve fiber layer (RNFL), and ganglion cell inner plexiform layer (GCIPL) using spectral-domain optical coherence tomography (SD-OCT) in the epiretinal membrane (ERM). The prospective study analyzed patients who visited our retinal clinic from June 2013 to January 2014. An experienced examiner measured the thicknesses twice using macular cube 512 × 128 and optic disc cube 200 × 200 scans. The repeatability of the thicknesses of the macula, RNFL, and GCIPL were compared using the intraclass correlation coefficient (ICC) of two groups based on the central macular thickness (group A, ≤ 450 μm; group B, > 450 μm). A total of 88 patients were analyzed. The average thicknesses of the central macula, RNFL, and GCIPL were 256.5, 96.6, and 84.4 μm, respectively, in the normal fellow eye and 412.3, 94.6, and 56.7 μm in the affected eye. The ICCs of the central macula, RNFL, and GCIPL were 0.995, 0.994, and 0.996, respectively, for the normal fellow eye and 0.991, 0.973, and 0.881 for the affected eye. The average thicknesses of the central macula, RNFL, and GCIPL in group A were 360.9, 93.5, and 63.4 μm, respectively, and the ICCs were 0.997, 0.987, and 0.995. The thicknesses in group B were 489.5, 96.2, and 46.6 μm, respectively, and the ICCs were 0.910, 0.942, and 0.603, significantly lower repeatability compared with group A (P macula.

  16. Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses

    Science.gov (United States)

    Maddox, Dennis M; Vessey, Kirstan A; Yarbrough, Gary L; Invergo, Brandon M; Cantrell, Donald R; Inayat, Samsoon; Balannik, Victoria; Hicks, Wanda L; Hawes, Norman L; Byers, Shannon; Smith, Richard S; Hurd, Ron; Howell, Douglas; Gregg, Ronald G.; Chang, Bo; Naggert, Jürgen K; Troy, John B; Pinto, Lawrence H; Nishina, Patsy M; McCall, Maureen A

    2008-01-01

    An electroretinogram (ERG) screen identified a mouse with a normal a-wave but lacking a b-wave, and as such it was designated no b-wave3 (nob3). The nob3 phenotype mapped to chromosome 11 in a region containing the metabotropic glutamate receptor 6 gene (Grm6). Sequence analyses of cDNA identified a splicing error in Grm6, introducing an insertion and an early stop codon into the mRNA of affected mice (designated Grm6nob3). Immunohistochemistry of the Grm6nob3 retina showed that GRM6 was absent. The ERG and visual behaviour abnormalities of Grm6nob3 mice are similar to Grm6nob4 animals, and similar deficits were seen in compound heterozygotes (Grm6nob4/nob3), indicating that Grm6nob3 is allelic to Grm6nob4. Visual responses of Grm6nob3 retinal ganglion cells (RGCs) to light onset were abnormal. Grm6nob3 ON RGCs were rarely recorded, but when they were, had ill-defined receptive field (RF) centres and delayed onset latencies. When Grm6nob3 OFF-centre RGC responses were evoked by full-field stimulation, significantly fewer converted that response to OFF/ON compared to Grm6nob4 RGCs. Grm6nob4/nob3 RGC responses verified the conclusion that the two mutants are allelic. We propose that Grm6nob3 is a new model of human autosomal recessive congenital stationary night blindness. However, an allelic difference between Grm6nob3 and Grm6nob4 creates a disparity in inner retinal processing. Because the localization of GRM6 is limited to bipolar cells in the On pathway, the observed difference between RGCs in these mutants is likely to arise from differences in their inputs. PMID:18687716

  17. Abnormalities of retinal ganglion cell complex at optical coherence tomography in patients with type 2 diabetes: a sign of diabetic polyneuropathy, not retinopathy.

    Science.gov (United States)

    Salvi, Laura; Plateroti, Pasquale; Balducci, Stefano; Bollanti, Lucilla; Conti, Francesco G; Vitale, Martina; Recupero, Santi Maria; Enrici, Maurizio Maurizi; Fenicia, Vito; Pugliese, Giuseppe

    2016-04-01

    To compare optical coherence tomography (OCT)-derived neuro-retinal parameters in patients with type 2 diabetes and non-diabetic controls and to evaluate their correlation with diabetic retinopathy (DR) and polyneuropathy (DPN). One-hundred consecutive patients with type 2 diabetes were examined by spectral-domain (SD) OCT for evaluating ganglion cell complex (GCC) and retinal nerve fibre layer (RNFL) thickness and two new pattern-based quantitative measures of GCC damage, global and focal loss volume (GLV and FLV). Fifty sex- and age-matched non-diabetic subjects served as control. RNFL thickness (101.0±10.6 vs. 106.4±10.3 μm, P=0.003) was significantly lower and GLV (6.58±4.98 vs. 4.52±3.10 %, P=0.008) and FLV (1.90±1.97 vs. 0.89±0.84 %, Pdiabetic versus control subjects. The OCT parameters did not differ significantly according to DR grade. Conversely, RNFL thickness was lower and GLV and FLV were higher in patients with versus those without DPN, and the extent of changes increased significantly with quartiles of DPN score. At both bivariate and multivariate analysis, OCT parameters, especially FLV, correlated significantly with DPN measures. The GCC is significantly affected in patients with type 2 diabetes and SD-OCT might represent a useful tool to detect DPN, but not DR in these individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Protective Effect of ALA in Crushed Optic Nerve Cat Retinal Ganglion Cells Using a New Marker RBPMS.

    Science.gov (United States)

    Wang, Yanling; Wang, Wenyao; Liu, Jessica; Huang, Xin; Liu, Ruixing; Xia, Huika; Brecha, Nicholas C; Pu, Mingliang; Gao, Jie

    2016-01-01

    In this study we first sought to determine whether RNA-binding protein with multiple splicing (RBPMS) can serve as a specific marker for cat retina ganglion cells (RGCs) using retrograde labeling and immunohistochemistry staining. RBPM was then used as an RGC marker to study RGC survival after optic nerve crush (ONC) and alpha-lipoic acid (ALA) treatment in cats. ALA treatment yielded a peak density of RBPMS-alpha cells within the peak isodensity zone (>60/mm2) which did not differ from ONC retinas. The area within the zone was significantly enlarged (control: 2.3%, ONC: 0.06%, ONC+ALA: 0.1%). As for the 10-21/mm2 zone, ALA treatment resulted in a significant increase in area (control: 34.5%, ONC: 12.1%, ONC+ALA: 35.9%). ALA can alleviate crush-induced RGC injury.

  19. Evaluation of Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness after Vitrectomy with Internal Limiting Membrane Peeling for Idiopathic Macular Holes

    Directory of Open Access Journals (Sweden)

    Alfonso L. Sabater

    2014-01-01

    Full Text Available Purpose. To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL thickness changes after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole repair using a high-resolution spectral-domain optical coherence tomography (SD-OCT. Methods. 32 eyes from 32 patients with idiopathic macular holes who underwent vitrectomy with internal limiting membrane peeling between January 2011 and July 2012 were retrospectively analyzed. GCIPL thickness was measured before surgery, and at one month and at six months after surgery. Values obtained from automated and semimanual SD-OCT segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA. Results. No significant differences were found between average GCIPL thickness values between preoperative and postoperative analysis. However, statistical significant differences were found in GCIPL thickness at the temporal macular quadrants at six months after surgery. Quality measurement analysis performed by automated segmentation revealed a significant number of segmentation errors. Semimanual segmentation slightly improved the quality of the results. Conclusion. SD-OCT analysis of GCIPL thickness found a significant reduction at the temporal macular quadrants at 6 months after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole.

  20. Evaluation of Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness after Vitrectomy with Internal Limiting Membrane Peeling for Idiopathic Macular Holes

    Science.gov (United States)

    Velázquez-Villoria, Álvaro; Zapata, Miguel A.; Figueroa, Marta S.; Suárez-Leoz, Marta; Arrevola, Luis; Teijeiro, María-Ángeles; García-Layana, Alfredo

    2014-01-01

    Purpose. To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness changes after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole repair using a high-resolution spectral-domain optical coherence tomography (SD-OCT). Methods. 32 eyes from 32 patients with idiopathic macular holes who underwent vitrectomy with internal limiting membrane peeling between January 2011 and July 2012 were retrospectively analyzed. GCIPL thickness was measured before surgery, and at one month and at six months after surgery. Values obtained from automated and semimanual SD-OCT segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA). Results. No significant differences were found between average GCIPL thickness values between preoperative and postoperative analysis. However, statistical significant differences were found in GCIPL thickness at the temporal macular quadrants at six months after surgery. Quality measurement analysis performed by automated segmentation revealed a significant number of segmentation errors. Semimanual segmentation slightly improved the quality of the results. Conclusion. SD-OCT analysis of GCIPL thickness found a significant reduction at the temporal macular quadrants at 6 months after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole. PMID:25110679

  1. The Effect of LASIK Procedure on Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Thickness in Myopic Eyes

    Directory of Open Access Journals (Sweden)

    Maja Zivkovic

    2017-01-01

    Full Text Available Purpose. To evaluate the effect of applied suction during microkeratome-assisted laser in situ keratomileusis (LASIK procedure on peripapillary retinal nerve fiber layer (RNFL thickness as well as macular ganglion cell-inner plexiform layer (GC-IPL thickness. Methods. 89 patients (124 eyes with established myopia range from −3.0 to −8.0 diopters and no associated ocular diseases were included in this study. RNFL and GC-IPL thickness measurements were performed by spectral domain optical coherence tomography (SD OCT one day before LASIK and at 1 and 6 months postoperatively. Results. Mean RNFL thickness prior to LASIK was 93.86±12.17 μm while the first month and the sixth month postoperatively were 94.01±12.04 μm and 94.46±12.27 μm, respectively. Comparing results, there is no significant difference between baseline, one month, and six months postoperatively for mean RNFL (p>0.05. Mean GC-IPL thickness was 81.70±7.47 μm preoperatively with no significant difference during the follow-up period (82.03±7.69 μm versus 81.84±7.64 μm; p>0.05. Conclusion. RNFL and GC-IPL complex thickness remained unaffected following LASIK intervention.

  2. Identification of synaptic pattern of NMDA receptor subunits upon direction-selective retinal ganglion cells in developing and adult mouse retina.

    Science.gov (United States)

    Lee, Jun-Seok; Kim, Hang-Gu; Jeon, Chang-Jin

    2017-06-01

    Direction selectivity of the retina is a unique mechanism and critical function of eyes for surviving. Direction-selective retinal ganglion cells (DS RGCs) strongly respond to preferred directional stimuli, but rarely respond to the opposite or null directional stimuli. These DS RGCs are sensitive to glutamate, which is secreted from bipolar cells. Using immunocytochemistry, we studied with the distributions of N-methyl-d-aspartate (NMDA) receptor subunits on the dendrites of DS RGCs in the developing and adult mouse retina. DS RGCs were injected with Lucifer yellow for identification of dendritic morphology. The triple-labeled images of dendrites, kinesin II, and NMDA receptor subunits were visualized using confocal microscopy and were reconstructed from high-resolution confocal images. Although our results revealed that the synaptic pattern of NMDA receptor subunits on dendrites of DS RGCs was not asymmetric in developing and adult mouse retina, they showed the anatomical connectivity of NMDA glutamatergic synapses onto DS RGCs and the developmental formation of the direction selectivity in the mouse retina. Through the comprehensive interpretation of the direction-selective neural circuit, this study, therefore, implies that the direction selectivity may be generated by the asymmetry of the excitatory glutamatergic inputs and the inhibitory inputs onto DS RGCs. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Dose-Dependent Protective Effect of Lithium Chloride on Retinal Ganglion Cells Is Interrelated with an Upregulated Intraretinal BDNF after Optic Nerve Transection in Adult Rats

    Directory of Open Access Journals (Sweden)

    Ming-Mei Wu

    2014-08-01

    Full Text Available Neuroprotection of lithium for axotomized retinal ganglion cells (RGCs is attributed to upregulated intraretinal Bcl-2. As lithium also upregulates brain-derived neurotrophic factor (BDNF which can rescue axotomized RGCs, it is hypothesized that lithium could protect RGCs through BDNF. This study investigated this hypothesis and a possible relationship between the dose and protection of lithium. All adult experimental rats received daily intraperitoneal injections of lithium chloride (LiCl at 30, 60 or 85 mg/kg·bw until they were euthanized 2, 7 or 14 days after left intraorbital optic nerve (ON transection. Our results revealed that RGC densities promoted and declined with increased dose of LiCl and the highest RGC densities were always in the 60 mg/kg·bw LiCl group at both 7 and 14 day points. Similar promotion and decline in the mRNA and protein levels of intraretinal BDNF were also found at the 14 day point, while such BDNF levels increased in the 30 mg/kg·bw LiCl group but peaked in the 60 and 85 mg/kg·bw LiCl groups at the 7 day point. These findings suggested that lithium can delay the death of axotomized RGCs in a dose-dependent manner within a certain period after ON injury and such beneficial effect is interrelated with an upregulated level of intraretinal BDNF.

  4. Expression of Nicotinic Acetylcholine Receptor α4 and β2 Subunits on Direction-Selective Retinal Ganglion Cells in the Rabbit.

    Science.gov (United States)

    Lee, Jun-Seok; Kim, Hyun-Jin; Ahn, Chang-Hyun; Jeon, Chang-Jin

    2017-02-28

    The direction selectivity of the retina is a distinct mechanism that is critical function of eyes for survival. The direction-selective retinal ganglion cells (DS RGCs) strongly respond to a preferred direction, but rarely respond to opposite direction or null directional visual stimuli. The DS RGCs are sensitive to acetylcholine, which is secreted from starburst amacrine cells (SACs) to the DS RGCs. Here, we investigated the existence and distribution of the nicotinic acetylcholine receptor (nAChR) α4 and β2 subunits on the dendritic arbors of the DS RGCs in adult rabbit retina using immunocytochemistry. The DS RGCs were injected with Lucifer yellow to identify their dendritic morphology. The double-labeled images of dendrites and nAChR subunits were visualized for reconstruction using high-resolution confocal microscopy. Although our results revealed that the distributional pattern of the nAChR subunits on the dendritic arbors of the DS RGCs was not asymmetric in the adult rabbit retina, the distribution of nAChR α4 and β2 subunits and molecular profiles of cholinergic inputs to DS RGCs in adult rabbit retina provide anatomical evidence for direction selectivity.

  5. Macular Ganglion Cell Layer and Peripapillary Retinal Nerve Fibre Layer Thickness in Patients with Unilateral Posterior Cerebral Artery Ischaemic Lesion: An Optical Coherence Tomography Study.

    Science.gov (United States)

    Anjos, Rita; Vieira, Luisa; Costa, Livio; Vicente, André; Santos, Arnaldo; Alves, Nuno; Amado, Duarte; Ferreira, Joana; Cunha, João Paulo

    2016-02-01

    The purpose of this study is to evaluate the macular ganglion cell layer (GCL) and peripapillary retinal nerve fibre layer (RNFL) thickness in patients with unilateral posterior cerebral artery (PCA) ischaemic lesions using spectral-domain optical coherence tomography (SD-OCT). A prospective, case-control study of patients with unilateral PCA lesion was conducted in the neuro-ophthalmology clinic of Centro Hospitalar Lisboa Central. Macular and peripapillary SD-OCT scans were performed in both eyes of each patient. Twelve patients with PCA lesions (stroke group) and 12 healthy normal controls were included in this study. Peripapillary RNFL comparison between both eyes of the same subject in the stroke group found a thinning in the superior-temporal ( p = 0.008) and inferior-temporal ( p = 0.023) sectors of the ipsilateral eye and nasal sector ( p = 0.003) of the contralateral eye. Macular GCL thickness comparison showed a reduction temporally in the ipsilateral eye ( p = 0.004) and nasally in the contralateral eye ( p = 0.002). Peripapillary RNFL thickness was significantly reduced in both eyes of patients with PCA compared with controls, affecting all sectors in the contralateral eye and predominantly temporal sectors in the ipsilateral eye. A statistically significant decrease in macular GCL thickness was found in both hemiretinas of both eyes of stroke patients when compared with controls ( p < 0.05). This study shows that TRD may play a role in the physiopathology of lesions of the posterior visual pathway.

  6. Evaluation of retinal nerve fibre layer, ganglion cell layer and choroidal thickness with optical coherence tomography in migraine patients: a case-control study.

    Science.gov (United States)

    Gunes, Aygül; Karadag, Ayse Sevgi; Yazgan, Serpil; Celik, Haci Ugur; Simsek, Ali

    2018-01-01

    Evaluation of retinal nerve fibre layer (RNFL), ganglion cell layer (GCL) and choroidal thickness (CT) with optical coherence tomography (OCT) in chronic migraine patients, to compare with healthy controls. Ninety-four eyes of 47 chronic migraine patients (Group 1) and 68 eyes of 34 healthy individuals (Group 2) were included in this prospective case-control study. The right and left eyes were separately evaluated. Mean peripapillary RNFL thicknesses, mean GCL measured from superior and inferior quadrants, and mean CT were measured at three different regions (central, 500 μm nasal and temporal region of the fovea). There was no statistically significant differences in RNFL between the two groups (p > 0.05), while CT values were significantly higher and GCL values were significantly lower in chronic migraine groups (p 0.05). In this study, we observed chronic migraine disease does not have any effect on peripapillary RNFL thickness; however, increases in CT and decreases in GCL thickness were observed in migraine patients. © 2017 Optometry Australia.

  7. Protective effects of a composition of Chinese herbs-Gurigumu-13 on retinal ganglion cell apoptosis in DBA/2J glaucoma mouse model

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    Qiu-Li Zhang

    2018-03-01

    Full Text Available AIM: To explore the concrete mechanism of a Mongolian compound medicine-Gurigumu-13 (GRGM for glaucoma treatment. METHODS: DBA/2J mice, as glaucoma models, were intragastric administrated with GRGM to study the effect of GRGM on retinal ganglion cells (RGCs. The loss of RGCs was evaluated with the number of RGCs and axons. The expression of the target protein of RGCs or mouse retinas was determined by Western blot. The relative content of malondialdehyde (MDA was examined by ELISA assay. RESULTS: GRGM distinctly improved retina damage via increasing the number of neurons, RGCs and axons in a concentration dependent manner. Meanwhile, GRGM obviously decreased the high level of MDA and the expression of oxidative stress-related proteins in retinas of DBA/2J mice, but promoted the expression of antioxidant proteins. Additionally, GRGM also significantly inhibited the protein expression of Bip and Chop, which were markers of endoplasmic reticulum stress-induced apoptosis. CONCLUSION: GRGM have obvious protective effects on RGCs in DBA/2J mice, and increase the number of RGCs and axons via inhibiting oxidative stress and endoplasmic reticulum stress.

  8. Decreased TNF Levels and Improved Retinal Ganglion Cell Survival in MMP-2 Null Mice Suggest a Role for MMP-2 as TNF Sheddase

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    Lies De Groef

    2015-01-01

    Full Text Available Matrix metalloproteinases (MMPs have been designated as both friend and foe in the central nervous system (CNS: while being involved in many neurodegenerative and neuroinflammatory diseases, their actions appear to be indispensable to a healthy CNS. Pathological conditions in the CNS are therefore often related to imbalanced MMP activities and disturbances of the complex MMP-dependent protease network. Likewise, in the retina, various studies in animal models and human patients suggested MMPs to be involved in glaucoma. In this study, we sought to determine the spatiotemporal expression profile of MMP-2 in the excitotoxic retina and to unravel its role during glaucoma pathogenesis. We reveal that intravitreal NMDA injection induces MMP-2 expression to be upregulated in the Müller glia. Moreover, MMP-2 null mice display attenuated retinal ganglion cell death upon excitotoxic insult to the retina, which is accompanied by normal glial reactivity, yet reduced TNF levels. Hence, we propose a novel in vivo function for MMP-2, as an activating sheddase of tumor necrosis factor (TNF. Given the pivotal role of TNF as a proinflammatory cytokine and neurodegeneration-exacerbating mediator, these findings generate important novel insights into the pathological processes contributing to glaucomatous neurodegeneration and into the interplay of neuroinflammation and neurodegeneration in the CNS.

  9. Ganglion Cysts

    Science.gov (United States)

    ... cyst Figure 3 - Cross-section of wrist showing the root of a ganglion cyst PDF Ganglion Cysts Related Conditions Trigger Finger Hand Tumors and Wrist Tumors de Quervain's Tenosynovitis Carpometacarpal Boss Other Links CME Mission Statement and ...

  10. A feed-forward regulation of endothelin receptors by c-Jun in human non-pigmented ciliary epithelial cells and retinal ganglion cells.

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    Junming Wang

    Full Text Available c-Jun, c-Jun N-terminal kinase(JNK and endothelin B (ETB receptor have been shown to contribute to the pathogenesis of glaucoma. Previously, we reported that an increase of c-Jun and CCAAT/enhancer binding protein β (C/EBPβ immunohistostaining is associated with upregulation of the ETB receptor within the ganglion cell layer of rats with elevated intraocular pressure (IOP. In addition, both transcription factors regulate the expression of the ETB receptor in human non-pigmented ciliary epithelial cells (HNPE. The current study addressed the mechanisms by which ET-1 produced upregulation of ET receptors in primary rat retinal ganglion cells (RGCs and HNPE cells. Treatment of ET-1 and ET-3 increased the immunocytochemical staining of c-Jun and C/EBPβ in primary rat RGCs and co-localization of both transcription factors was observed. A marked increase in DNA binding activity of AP-1 and C/EBPβ as well as elevated protein levels of c-Jun and c-Jun-N-terminal kinase (JNK were detected following ET-1 treatment in HNPE cells. Overexpression of ETA or ETB receptor promoted the upregulation of c-Jun and also elevated its promoter activity. In addition, upregulation of C/EBPβ augmented DNA binding and mRNA expression of c-Jun, and furthermore, the interaction of c-Jun and C/EBPβ was confirmed using co-immunoprecipitation. Apoptosis of HNPE cells was identified following ET-1 treatment, and overexpression of the ETA or ETB receptor produced enhanced apoptosis. ET-1 mediated upregulation of c-Jun and C/EBPβ and their interaction may represent a novel mechanism contributing to the regulation of endothelin receptor expression. Reciprocally, c-Jun was also found to regulate the ET receptors and C/EBPβ appeared to play a regulatory role in promoting expression of c-Jun. Taken together, the data suggests that ET-1 triggers the upregulation of c-Jun through both ETA and ETB receptors, and conversely c-Jun also upregulates endothelin receptor expression

  11. Ganglion cell complex and retinal nerve fiber layer measured by fourier-domain optical coherence tomography for early detection of structural damage in patients with preperimetric glaucoma

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    Rolle T

    2011-07-01

    Full Text Available Teresa Rolle, Cristina Briamonte, Daniela Curto, Federico Maria GrignoloEye Clinic, Section of Ophthalmology, Department of Clinical Physiopathology, University of Torino, Torino, ItalyAims: To evaluate the capability of Fourier-domain optical coherence tomography (FD-OCT to detect structural damage in patients with preperimetric glaucoma.Methods: A total of 178 Caucasian subjects were enrolled in this cohort study: 116 preperimetric glaucoma patients and 52 healthy subjects. Using three-dimensional FD-OCT, the participants underwent imaging of the ganglion cell complex (GCC and the optic nerve head. Sensitivity, specificity, likelihood ratios, and predictive values were calculated for all parameters at the first and fifth percentiles. Areas under the curves (AUCs were generated for all parameters and were compared (Delong test. For both the GCC and the optic nerve head protocols, the OR logical disjunction (Boolean logic operator was calculated.Results: The AUCs didn’t significantly differ. Macular global loss volume had the largest AUC (0.81. Specificities were high at both the fifth and first percentiles (up to 97%, but sensitivities were low, especially at the first percentile (55%–27%.Conclusion: Macular and papillary diagnostic accuracies did not differ significantly based on the 95% confidence interval. The computation of the Boolean OR operator has been found to boost diagnostic accuracy. Using the software-provided classification, sensitivity and diagnostic accuracy were low for both the retinal nerve fiber layer and the GCC scans. FD-OCT does not seem to be decisive for early detection of structural damage in patients with no functional impairment. This suggests that there is a need for analysis software to be further refined to enhance glaucoma diagnostic capability.Keywords: OCT, RNFL, GCC, diagnostic accuracy 

  12. LONGITUDINAL CHANGES IN THICKNESSES OF THE MACULA, GANGLION CELL-INNER PLEXIFORM LAYER, AND RETINAL NERVE FIBER LAYER AFTER VITRECTOMY: A 12-Month Observational Study.

    Science.gov (United States)

    Lim, Hyung-Bin; Lee, Min-Woo; Kwak, Baek-Soo; Jo, Young-Joon; Kim, Jung-Yeul

    2018-01-01

    To analyze longitudinal changes in the thicknesses of the macula, ganglion cell-inner plexiform layer (GC-IPL), and peripapillary retinal nerve fiber layer (RNFL) after vitrectomy. Thirty-eight patients diagnosed with intraocular lens (IOL) dislocation without evidence of other vitreoretinal diseases were included. They underwent conventional vitrectomy and IOL transscleral fixation, with a follow-up of 12 months. Using spectral domain optical coherence tomography, the thicknesses of the macula, GC-IPL, and peripapillary RNFL in the vitrectomized and fellow control eyes were measured. Various optic nerve head parameters were also determined. Optical coherence tomography showed that there were no significant differences in postoperative central macular thickness compared with baseline values. The average GC-IPL thickness increased 1 month after surgery from baseline (P = 0.038). The average RNFL thickness increased from baseline at 1 month (P = 0.001) and 3 months (P = 0.011) after vitrectomy. The mean foveal, GC-IPL, and RNFL thicknesses of the study eyes compared with the fellow control eyes increased at 1 month (P = 0.034), 1 month (P = 0.048), and 1 month (P = 0.013) to 3 months (P = 0.038), respectively, after surgery. However, no significant differences were found in intraocular pressure or optic nerve head parameters between the study and fellow control eyes at 12 months after surgery. Transient increases in the thickness of the macula and GC-IPL were observed at 1 month after vitrectomy, and the postoperative RNFL thickness increased until 3 months after surgery, after which it returned to preoperative levels. There was no significant change in intraocular pressure or optic nerve head parameters before and after surgery.

  13. Visual Neurons in the Superior Colliculus Innervated by Islet2+ or Islet2− Retinal Ganglion Cells Display Distinct Tuning Properties

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    Rachel B. Kay

    2017-10-01

    Full Text Available Throughout the visual system, different subtypes of neurons are tuned to distinct aspects of the visual scene, establishing parallel circuits. Defining the mechanisms by which such tuning arises has been a long-standing challenge for neuroscience. To investigate this, we have focused on the retina’s projection to the superior colliculus (SC, where multiple visual neuron subtypes have been described. The SC receives inputs from a variety of retinal ganglion cell (RGC subtypes; however, which RGCs drive the tuning of different SC neurons remains unclear. Here, we pursued a genetic approach that allowed us to determine the tuning properties of neurons innervated by molecularly defined subpopulations of RGCs. In homozygous Islet2-EphA3 knock-in (Isl2EA3/EA3 mice, Isl2+ and Isl2− RGCs project to non-overlapping sub-regions of the SC. Based on molecular and anatomic data, we show that significantly more Isl2− RGCs are direction-selective (DS in comparison with Isl2+ RGCs. Targeted recordings of visual responses from each SC sub-region in Isl2EA3/EA3 mice revealed that Isl2− RGC-innervated neurons were significantly more DS than those innervated by Isl2+ RGCs. Axis-selective (AS neurons were found in both sub-regions, though AS neurons innervated by Isl2+ RGCs were more tightly tuned. Despite this segregation, DS and AS neurons innervated by Isl2+ or Isl2− RGCs did not differ in their spatial summation or spatial frequency (SF tuning. Further, we did not observe alterations in receptive field (RF size or structure of SC neurons innervated by Isl2+ or Isl2− RGCs. Together, these data show that innervation by Isl2+ and Isl2− RGCs results in distinct tuning in the SC and set the stage for future studies investigating the mechanisms by which these circuits are built.

  14. Etanercept, a widely used inhibitor of tumor necrosis factor-α (TNF-α, prevents retinal ganglion cell loss in a rat model of glaucoma.

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    Miin Roh

    Full Text Available Visual loss in glaucoma is associated with pathological changes in retinal ganglion cell (RGC axons and a slow decline in the RGC population. Age and elevated intraocular pressure (IOP are the main risk factors for glaucomatous loss of vision. Several studies have implicated the proinflammatory cytokine tumor necrosis factor-α (TNF-α as a link between elevated IOP and RGC death, but the cellular source of TNF-α and its causative role in RGC death remain uncertain. Here, using a rat model of glaucoma, we investigated the source of elevated TNF-α and examined whether Etanercept, a TNF-α blocker that is in common clinical use for other indications, is protective against RGC death.Episcleral vein cauterization (EVC caused intraocular pressure (IOP to be elevated for at least 28 days. IOP elevation resulted in a dramatic increase in TNF-α levels within a few days, axonal degeneration, and a 38% loss of RGCs by 4 weeks. Immunostaining coupled with confocal microscopy showed that OHT induced robust induction of TNF-α in Iba-1-positive microglia around the optic nerve head (ONH. Despite persistent elevation of IOP, Etanercept reduced microglial activation, TNF-α levels, axon degeneration in the optic nerve, and the loss of RGCs.Ocular hypertension (OHT triggers an inflammatory response characterized by the appearance of activated microglia around the ONH that express TNF-α. Blocking TNF-α activity with a clinically approved agent inhibits this microglial response and prevents axonal degeneration and loss of RGCs. These findings suggest a new treatment strategy for glaucoma using TNF-α antagonists or suppressors of inflammation.

  15. Comparison of longitudinal changes in circumpapillary retinal nerve fiber layer and ganglion cell complex thickness after acute primary angle closure: a 12-month prospective study.

    Science.gov (United States)

    Jin, Sang Wook; Lee, Sae Mi

    2018-03-01

    To compare longitudinal changes in circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell complex (GCC) thicknesses and factors that are related to changes in cpRNFL and GCC thicknesses after acute primary angle closure (APAC). A prospective consecutive case series. This study was a prospective, consecutive case series study including 64 eyes of 64 subjects with APAC. cpRNFL and GCC thicknesses were measured by RTVue-100 OCT. To measure cpRNFL and GCC thicknesses, the "three-dimensional (3D) optic disc scan and ONH scan" and "GCC" scan mode were used. Differences in cpRNFL and GCC thicknesses between the affected eye and fellow eye were compared, and logistic regression analysis was performed to investigate the factors associated with longitudinal changes in cpRNFL and GCC thicknesses. The average, superior and inferior cpRNFL, and GCC thicknesses were thicker in the affected eye than in the fellow eye within 1 week after remission and gradually decreased up to 12 months after remission. Compared with the cpRNFL and GCC thicknesses at 1 week after remission, the cpRNFL and GCC thicknesses at 1 month, 3 months, 6 months, and 12 months after remission were significantly thinner. Logistic regression analysis revealed that a longer duration from the onset of symptoms to adjustment of treatment (cpRNFL: odds ratio = 0.865, p = 0.003) (GCC: odds ratio = 0.824, p = 0.001) was associated with abnormal cpRNFL and GCC thicknesses. A week after APAC both cpRNFL and GCC thicknesses were thicker in the affected eye than in the fellow eye and further decreased up to 12 months post APAC. A longer duration from the onset of symptoms to adjustment of treatment was associated with cpRNFL and GCC loss after APAC.

  16. Roles of PI3K and JAK pathways in viability of retinal ganglion cells after acute elevation of intraocular pressure in rats with different autoimmune backgrounds

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    Wang Ningli

    2008-08-01

    Full Text Available Abstract Background We recently showed that whereas inhibition of PI3K/akt or JAK/STAT pathway promoted retinal ganglion cell (RGC survival after optic nerve (ON injury in Fischer 344 (F344 rats, the same inhibition resulted in aggravated RGC loss after acute intraocular pressure (IOP elevation in Sprague Dawley (SPD rats. In addition, the responses of macrophages to ON injury and acute IOP elevation were different between F344 and Lewis rats, i.e., different autoimmune profiles. Using an acute IOP elevation paradigm in this study, we investigated 1 whether autoimmune background influences PI3K/akt and JAK/STAT functions by examining the effect of PI3K/akt and JAK/STAT pathway inhibition on RGC survival in F344 and Lewis rats, and 2 whether differential actions of macrophages occur in PI3K/akt and JAK/STAT pathways-dependent modulation of RGC survival. IOP elevation was performed at 110 mmHg for 2 hours. PI3K/akt and JAK/STAT pathway inhibitors were applied intravitreally to block their respective pathway signaling transduction. Because macrophage invasion was seen in the eye after the pathway inhibition, to examine the role of these pathways independent of macrophages, macrophages in the retina were removed by intravitreal application of clodronate liposomes. Viable RGCs were retrogradely labelled by FluoroGold 40 hours before animal sacrifice. Results Similar to what was previously observed, significantly more RGCs were lost in Lewis than F344 rats 3 weeks after acute IOP elevation. As in SPD rats, inhibition of the PI3K/akt or JAK/STAT pathway increased the loss of RGCs in both F344 and Lewis rats. Removal of macrophages in the eye by clodronate liposomes reduced RGC loss due to pathway inhibition in both strains. Conclusion This study demonstrates that following acute IOP elevation 1 PI3K/akt and JAK/STAT pathways mediate RGC survival in both F344 and Lewis rats, 2 autoimmune responses do not influence the functions of these two pathways

  17. Correlation Between En Face Optical Coherence Tomography Defects of the Inner Retinal Layers and Ganglion Cell Inner Plexiform Layer Analysis After Internal Limiting Membrane Peeling for Idiopathic Full-Thickness Macular Hole.

    Science.gov (United States)

    Sabry, Dalia; El-Kannishy, Amr; Kamel, Rania; Abou Samra, Waleed

    2016-07-01

    The purpose of this study was to report en face optical coherence tomography (OCT) inner retinal changes after internal limiting membrane (ILM) peeling for idiopathic full-thickness macular hole (IFTMH) and to correlate these findings with macular ganglion cell inner plexiform layer (GC-IPL) analysis. This prospective study included 20 patients with IFTMH treated using pars plana vitrectomy with ILM peeling. All patients were analyzed using en face OCT at 6 months after surgery to determinate the effect of ILM peeling on the inner retinal layers. Correlation between the GC-IPL en face OCT findings and that obtained by three-dimensional volumetric OCT scanning also was performed. Seven patients (35%) showed defects in the retinal nerve fiber layer (RNFL) that appeared as multiple dark dots with no visible defects at the GC-IPL, either with en face OCT or 3D volumetric OCT scanning. Thirteen patients (65%) showed a similar combination of RNFL defects and well-circumscribed defects in the underlying GC-IPL. These defects could be visualized on en face OCT display, and they correlated with areas of GC-IPL thinning detected in the 3D volumetric OCT scanning. With ILM peeling, en face OCT scanning showed two forms of inner retinal layers changes. The first form was the concentric macular dark spots (CMDS) with intact GC-IPL. The second form appeared in the CMDS with evident localized defects in the underlying GC-IPL. These defects correlate with the areas of GC-IPL thinning detected using 3D volumetric OCT scanning.

  18. Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse

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    Vandewauw Ine

    2013-02-01

    Full Text Available Abstract Background Somatosensory nerve fibres arising from cell bodies within the trigeminal ganglia (TG in the head and from a string of dorsal root ganglia (DRG located lateral to the spinal cord convey endogenous and environmental stimuli to the central nervous system. Although several members of the transient receptor potential (TRP superfamily of cation channels have been implicated in somatosensation, the expression levels of TRP channel genes in the individual sensory ganglia have never been systematically studied. Results Here, we used quantitative real-time PCR to analyse and compare mRNA expression of all TRP channels in TG and individual DRGs from 27 anatomically defined segments of the spinal cord of the mouse. At the mRNA level, 17 of the 28 TRP channel genes, TRPA1, TRPC1, TRPC3, TRPC4, TRPC5, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPML1 and TRPP2, were detectable in every tested ganglion. Notably, four TRP channels, TRPC4, TRPM4, TRPM8 and TRPV1, showed statistically significant variation in mRNA levels between DRGs from different segments, suggesting ganglion-specific regulation of TRP channel gene expression. These ganglion-to-ganglion differences in TRP channel transcript levels may contribute to the variability in sensory responses in functional studies. Conclusions We developed, compared and refined techniques to quantitatively analyse the relative mRNA expression of all TRP channel genes at the single ganglion level. This study also provides for the first time a comparative mRNA distribution profile in TG and DRG along the entire vertebral column for the mammalian TRP channel family.

  19. Developmental changes in NMDA receptor subunit composition at ON and OFF bipolar cell synapses onto direction-selective retinal ganglion cells.

    Science.gov (United States)

    Stafford, Benjamin K; Park, Silvia J H; Wong, Kwoon Y; Demb, Jonathan B

    2014-01-29

    In the developing mouse retina, spontaneous and light-driven activity shapes bipolar→ganglion cell glutamatergic synapse formation, beginning around the time of eye-opening (P12-P14) and extending through the first postnatal month. During this time, glutamate release can spill outside the synaptic cleft and possibly stimulate extrasynaptic NMDA-type glutamate receptors (NMDARs) on ganglion cells. Furthermore, the role of NMDARs during development may differ between ON and OFF bipolar synapses as in mature retina, where ON synapses reportedly include extrasynaptic NMDARs with GluN2B subunits. To better understand the function of glutamatergic synapses during development, we made whole-cell recordings of NMDAR-mediated responses, in vitro, from two types of genetically identified direction-selective ganglion cells (dsGCs): TRHR (thyrotropin-releasing hormone receptor) and Drd4 (dopamine receptor 4). Both dsGC types responded to puffed NMDA between P7 and P28; and both types exhibited robust light-evoked NMDAR-mediated responses at P14 and P28 that were quantified by conductance analysis during nicotinic and GABA(A) receptor blockade. For a given cell type and at a given age, ON and OFF bipolar cell inputs evoked similar NMDAR-mediated responses, suggesting that ON-versus-OFF differences in mature retina do not apply to the cell types or ages studied here. At P14, puff- and light-evoked NMDAR-mediated responses in both dsGCs were partially blocked by the GluN2B antagonist ifenprodil, whereas at P28 only TRHR cells remained ifenprodil-sensitive. NMDARs contribute at both ON and OFF bipolar cell synapses during a period of robust activity-dependent synaptic development, with declining GluN2B involvement over time in specific ganglion cell types.

  20. THICKNESS OF THE MACULA, RETINAL NERVE FIBER LAYER, AND GANGLION CELL-INNER PLEXIFORM LAYER IN THE AGE-RELATED MACULAR DEGENERATION: The Repeatability Study of Spectral Domain Optical Coherence Tomography.

    Science.gov (United States)

    Shin, Il-Hwan; Lee, Woo-Hyuk; Lee, Jong-Joo; Jo, Young-Joon; Kim, Jung-Yeul

    2018-02-01

    To determine the repeatability of measuring the thickness of the central macula, retinal nerve fiber layer, and ganglion cell-inner plexiform layer (GC-IPL) using spectral domain optical coherence tomography (Cirrus HD-OCT) in eyes with age-related macular degeneration. One hundred and thirty-four eyes were included. The measurement repeatability was assessed by an experienced examiner who performed two consecutive measurements using a 512 × 128 macular cube scan and a 200 × 200 optic disk cube scan. To assess changes in macular morphology in patients with age-related macular degeneration, the patients were divided into the following three groups according to the central macular thickness (CMT): A group, CMT 300 μm. Measurement repeatability was assessed using test-retest variability, a coefficient of variation, and an intraclass correlation coefficient. The mean measurement repeatability for the central macular, retinal nerve fiber layer, and GC-IPL thickness was high in the B group. The mean measurement repeatability for both the central macula and retinal nerve fiber layer thickness was high in the A and C groups, but was lower for the GC-IPL thickness. The measurement repeatability for GC-IPL thickness was high in the B group, but low in the A group and in the C group. The automated measurement repeatability for GC-IPL thickness was significantly lower in patients with age-related macular degeneration with out of normal CMT range. The effect of changes in macular morphology should be considered when analyzing GC-IPL thicknesses in a variety of ocular diseases.

  1. Significant changes in endogenous retinal gene expression assessed 1 year after a single intraocular injection of AAV-CNTF or AAV-BDNF

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    Chrisna J LeVaillant

    2016-01-01

    Full Text Available Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV vectors encoding brain-derived neurotrophic factor (BDNF or ciliary derived neurotrophic factor (CNTF promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression. One year after the intravitreal injection of AAV-green fluorescent protein (GFP, bi-cistronic AAV-BDNF-GFP or AAV-CNTF-GFP, mRNA was extracted and analyzed using custom 96 well polymerase chain reaction arrays. Of 93 test genes, 56% showed significantly altered expression in AAV-BDNF-GFP and/or AAV-CNTF-GFP retinas compared with AAV-GFP controls. Of these genes, 73% showed differential expression in AAV-BDNF versus AAV-CNTF injected eyes. To focus on retinal ganglion cell changes, quantitative polymerase chain reaction was undertaken on mRNA (16 genes obtained from fixed retinal sections in which the ganglion cell layer was enriched. The sign and extent of fold changes in ganglion cell layer gene expression differed markedly from whole retinal samples. Sustained and global alteration in endogenous mRNA expression after gene therapy should be factored into any interpretation of experimental/clinical outcomes, particularly when introducing factors into the central nervous system that require secretion to evoke functionality.

  2. Synergistic effects of osteonectin and brain-derived neurotrophic factor on axotomized retinal ganglion cells neurite outgrowth via the mitogen-activated protein kinase-extracellular signal-regulated kinase 1/2 pathways.

    Science.gov (United States)

    Ma, C H E; Bampton, E T W; Evans, M J; Taylor, J S H

    2010-01-20

    Our previous study identified osteonectin (ON) in a screen of factors made by Schwann cells (SCs) which promoted peripheral and central neurons survival and neuritogenesis, however, the mechanisms of ON promoting effects are largely unknown. In the present study, we investigated the effects of ON-deficient SC-conditioned medium (SCCM) and molecular mechanisms of ON, in regulating retinal ganglion cells (RGCs) survival and neurite outgrowth. Neonatal rat RGCs and SCs were purified by immunopanning technique. RGC survival and neuritogenesis reduced significantly when treated with either ON-null mice SCCM or ON-immunodepleted (IP) SCCM (Pshowed the synergistic effects of ON and brain-derived neurotrophic factor (BDNF) in promoting RGCs growth and the involvement of ON in two major neurotrophin-mediated signaling pathways, PI-3K-Akt and MAPK-Erk1/2. ON alone activated Akt phosphorylation and increased survival. Blockage of TrkB signalling pathway by TrkB-Fc chimera (BDNF scavenger) or K252a in ON-treated cultures reduced Akt-P level significantly. This suggests that ON induces BDNF synthesis and secretion from RGCs. The enhancement of neuritogenesis and Erk1/2 phosphorylation by ON in BDNF-treated cultures further demonstrate the signaling pathways responsible for the synergistic effect of ON on BDNF-induced neurite outgrowth. To the best of our knowledge, this is the first report showing the synergistic effects of ON on classical neurotrophins which participate in the same signalling pathways in regulating RGC neurite outgrowth.

  3. Size of the Optic Nerve Head and Its Relationship with the Thickness of the Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Patients with Primary Open Angle Glaucoma

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    Nobuko Enomoto

    2015-01-01

    Full Text Available Purpose. To evaluate the relationships among the optic nerve head (ONH area, macular ganglion cell complex (mGCC thickness, circumpapillary retinal nerve fiber layer (cpRNFL thickness, and visual field defects in patients with primary open angle glaucoma (POAG. Methods. This retrospective study included 90 eyes of 90 patients with POAG. The ONH area, rim area, mGCC thickness, and cpRNFL thickness were measured using optical coherence tomography. Mean deviation (MD was measured using standard automated perimetry. The relationships among clinical factors including age, refraction, the ONH area, the rim area, the mGCC thickness, the cpRNFL thickness, and MD were evaluated using correlation coefficients and multiple regression analyses. Results. The significant correlation of the ONH area with refraction (r=0.362, P<0.001, the mGCC thickness (r=0.225, P=0.033, and the cpRNFL thickness (r=0.253, P=0.016 was found. Multiple regression analysis showed that the ONH area, rim area, and MD were selected as significant contributing factors to explain the mGCC thickness and cpRNFL thickness. No factor was selected to explain MD. Conclusions. The ONH area, in other words, the disc size itself may affect the mGCC thickness and cpRNFL thickness in POAG patients.

  4. Topography of ganglion cell production in the cat's retina

    International Nuclear Information System (INIS)

    Walsh, C.; Polley, E.H.

    1985-01-01

    The ganglion cells of the cat's retina form several classes distinguishable in terms of soma size, axon diameter, dendritic morphology, physiological properties, and central connections. Labeling with [ 3 H]thymidine shows that the ganglion cells which survive in the adult are produced as several temporally shifted, overlapping waves: medium-sized cells are produced before large cells, whereas the smallest ganglion cells are produced throughout the period of ganglion cell generation. Large cells and medium-sized cells show the same distinctive pattern of production, forming rough spirals around the area centralis. The oldest cells tend to lie superior and nasal to the area centralis, whereas cells in the inferior nasal retina and inferior temporal retina are, in general, progressively younger. Within each retinal quadrant, cells nearer the area centralis tend to be older than cells in the periphery, but there is substantial overlap. The retinal raphe divides the superior temporal quadrant into two zones with different patterns of cell addition. Superior temporal retina near the vertical meridian adds cells only slightly later than superior nasal retina, whereas superior temporal retina near the horizontal meridian adds cells very late, contemporaneously with inferior temporal retina. The broader wave of production of smaller ganglion cells seems to follow this same spiral pattern at its beginning and end. The presence of the area centralis as a nodal point about which ganglion cell production in the retinal quadrants pivots suggests that the area centralis is already an important retinal landmark even at the earliest stages of retinal development

  5. Dopaminergic modulation of tracer coupling in a ganglion-amacrine cell network

    OpenAIRE

    MILLS, STEPHEN L.; XIA, XIAO-BO; HOSHI, HIDEO; FIRTH, SALLY I.; RICE, MARGARET E.; FRISHMAN, LAURA J.; MARSHAK, DAVID W.

    2007-01-01

    Many retinal ganglion cells are coupled via gap junctions with neighboring amacrine cells and ganglion cells. We investigated the extent and dynamics of coupling in one such network, the OFF α ganglion cell of rabbit retina and its associated amacrine cells. We also observed the relative spread of Neurobiotin injected into a ganglion cell in the presence of modulators of gap junctional permeability. We found that gap junctions between amacrine cells were closed via stimulation of a D1 dopamin...

  6. Visual field defects and changes in macular retinal ganglion cell complex thickness in eyes with intrachoroidal cavitation are similar to those in early glaucoma

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    Okuma S

    2016-06-01

    Full Text Available Shinichi Okuma,1 Shiro Mizoue,2,3 Yuichi Ohashi3 1Department of Ophthalmology, Sumitomo Besshi Hospital, Niihama-shi, 2Department of Ophthalmology, Minami-Matsuyama Hospital, Matsuyama-shi, 3Department of Ophthalmology, Ehime University School of Medicine, Toon-shi, Ehime, Japan Background/aims: To examine the characteristics of visual field defects and optical coherence tomography (OCT findings in eyes with intrachoroidal cavitation (ICC and investigate the similarities between these results and glaucomatous changes.Methods: We retrospectively analyzed patients diagnosed with ICC based on peripapillary radial cross-sectional scans performed with OCT. Visual field was measured with the Humphrey automated visual field analyzer SITA standard central 24-2 program, and macular ganglion cell complex (GCC thickness was measured in 9×9 mm areas on OCT. The positive rates for the Anderson criteria, site of visual field defect, and mean GCC thickness in each quadrant were compared; the association between these results and ICC location was assessed.Results: Fifteen eyes from eleven patients (five males and six females; mean age, 54.6±10.7 years were selected for investigation. ICC was detected in the inferior temporal side of the optic disc in all studied eyes. The positive rate for the Anderson criteria was 73.3% (11/15 eyes. Visual field defects were most commonly observed in the cluster that corresponded to the superior Bjerrum area (53.3%; 8/15 eyes. GCC thickness was significantly lower in the inferior side, where the ICC was located, than the superior side, where the ICC was absent (P=0.0001. GCC thinning that correlated with ICC was observed in 66.7% (10/15 eyes of the ICC eyes.Conclusion: Visual field and GCC findings on OCT in ICC eyes are extremely similar to those observed in superior visual field defect-type early glaucoma, indicating a possible difficulty in distinguishing the two conditions. Keywords: intrachoroidal cavitation, visual

  7. Perceptual Fading without Retinal Adaptation

    Science.gov (United States)

    Hsieh, Po-Jang; Colas, Jaron T.

    2012-01-01

    A retinally stabilized object readily undergoes perceptual fading and disappears from consciousness. This startling phenomenon is commonly believed to arise from local bottom-up sensory adaptation to edge information that occurs early in the visual pathway, such as in the lateral geniculate nucleus of the thalamus or retinal ganglion cells. Here…

  8. Can optical coherence tomography predict early retinal microvascular pathology in type 1 diabetic adolescents without minimal diabetic retinopathy? A single-centre study.

    Science.gov (United States)

    Elhabashy, Safinaz Adel; Elbarbary, Nancy Samir; Nageb, Karim Magdy; Mohammed, Mai Mostafa

    2015-01-01

    Optical coherence tomography (OCT) has been proven useful in measuring retinal thickness and volumes in patients with diabetes. To test whether OCT is able to identify early retinal changes and its potential correlations with metabolic parameters and other microvascular complications. Thirty patients with type 1 diabetes without minimal diabetic retinopathy (MDR) (17 males, 13 females, aged 14.3±2.4 years) compared with age-matched healthy volunteers were examined with OCT. Diabetes duration, anthropometric measurements, HbA1c, other microvascular complications (nephropathy, autonomic and peripheral neuropathy) and total serum cholesterol were determined. No statistically significant differences were found between patients with (n=15) and without microvascular complications (n=15) compared to controls regarding retinal volume, nerve fibre layer volume (temporal and nasal quadrants) and ganglion cell layer area in both eyes. No correlation was found between the ganglion cell layer area and the clinical and laboratory characteristics of the patients, except a negative correlation with total serum cholesterol (r=-0.369, p=0.049). The best cut-off value of ganglion cell layer area to detect the level at which thinning of this layer occurs was >1900 pixels. Our study suggests that there is no advantage in performing OCT routinely in patients with type 1 diabetes mellitus without MDR. OCT did not show changes in retinal thickness in those patients compared to control. So OCT did not seem to be useful in the preclinical stages of diabetic retinopathy. Therefore, the conventional diagnostic methods are mandatory to detect early diabetic retinopathy.

  9. Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization

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    Takahito Nakama

    2017-03-01

    Full Text Available Retinal neovascularization (NV due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.

  10. A mouse ocular explant model that enables the study of living optic nerve head events after acute and chronic intraocular pressure elevation: Focusing on retinal ganglion cell axons and mitochondria.

    Science.gov (United States)

    Kimball, Elizabeth C; Pease, Mary E; Steinhart, Matthew R; Oglesby, Ericka N; Pitha, Ian; Nguyen, Cathy; Quigley, Harry A

    2017-07-01

    We developed an explant model of the mouse eye and optic nerve that facilitates the study of retinal ganglion cell axons and mitochondria in the living optic nerve head (ONH) in an ex vivo environment. Two transgenic mouse strains were used, one expressing yellow fluorescent protein in selected axons and a second strain expressing cyan fluorescent protein in all mitochondria. We viewed an explanted mouse eye and optic nerve by laser scanning microscopy at and behind the ONH, the site of glaucoma injury. Explants from previously untreated mice were studied with the intraocular pressure (IOP) set artificially at normal or elevated levels for several hours. Explants were also studied from eyes that had undergone chronic IOP elevation from 14 h to 6 weeks prior to ex vivo study. Image analysis in static images and video of individual mitochondria or axonal structure determined effects of acute and chronic IOP elevation. At normal IOP, fluorescent axonal structure was stable for up to 3 h under ex vivo conditions. After chronic IOP elevation, axonal integrity index values indicated fragmentation of axon structure in the ONH. In mice with fluorescent mitochondria, the normal density decreased with distance behind the ONH by 45% (p = 0.002, t-test). Density increased with prior chronic IOP elevation to 21,300 ± 4176 mitochondria/mm 2 compared to control 16,110 ± 3159 mitochondria/mm 2 (p = 0.025, t-test), but did not increase significantly after 4 h, acute IOP elevation (1.5% decrease in density, p = 0.83, t-test). Mean normal mitochondrial length of 2.3 ± 1.4 μm became 13% smaller after 4 h of IOP elevation ex vivo compared to baseline (p = 0.015, t-test, N-10). Normal mitochondrial speed of movement was significantly slower in the anterograde direction (towards the brain) than retrograde, but there were more mitochondria in motion and traveling longer lengths in anterograde direction. The percent of mitochondria in motion decreased by >50

  11. Whole number, distribution and co-expression of brn3 transcription factors in retinal ganglion cells of adult albino and pigmented rats.

    Directory of Open Access Journals (Sweden)

    Francisco M Nadal-Nicolás

    Full Text Available The three members of the Pou4f family of transcription factors: Pou4f1, Pou4f2, Pou4f3 (Brn3a, Brn3b and Brn3c, respectively play, during development, essential roles in the differentiation and survival of sensory neurons. The purpose of this work is to study the expression of the three Brn3 factors in the albino and pigmented adult rat. Animals were divided into these groups: i untouched; ii fluorogold (FG tracing from both superior colliculli; iii FG-tracing from one superior colliculus; iv intraorbital optic nerve transection or crush. All retinas were dissected as flat-mounts and subjected to single, double or triple immunohistofluorescence The total number of FG-traced, Brn3a, Brn3b, Brn3c or Brn3 expressing RGCs was automatically quantified and their spatial distribution assessed using specific routines. Brn3 factors were studied in the general RGC population, and in the intrinsically photosensitive (ip-RGCs and ipsilateral RGC sub-populations. Our results show that: i 70% of RGCs co- express two or three Brn3s and the remaining 30% express only Brn3a (26% or Brn3b; ii the most abundant Brn3 member is Brn3a followed by Brn3b and finally Brn3c; iii Brn3 a-, b- or c- expressing RGCs are similarly distributed in the retina; iv The vast majority of ip-RGCs do not express Brn3; v The main difference between both rat strains was found in the population of ipsilateral-RGCs, which accounts for 4.2% and 2.5% of the total RGC population in the pigmented and albino strain, respectively. However, more ipsilateral-RGCs express Brn3 factors in the albino than in the pigmented rat; vi RGCs that express only Brn3b and RGCs that co-express the three Brn3 members have the biggest nuclei; vii After axonal injury the level of Brn3a expression in the surviving RGCs decreases compared to control retinas. Finally, this work strengthens the validity of Brn3a as a marker to identify and quantify rat RGCs.

  12. Melanopsin expressing human retinal ganglion cells

    DEFF Research Database (Denmark)

    Hannibal, Jens; Christiansen, Anders Tolstrup; Heegaard, Steffen

    2017-01-01

    microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1...

  13. Thorny ganglion cells in marmoset retina: Morphological and neurochemical characterization with antibodies against calretinin.

    Science.gov (United States)

    Chandra, Ashleigh J; Lee, Sammy C S; Grünert, Ulrike

    2017-12-15

    In primates, over 17 morphological types of retinal ganglion cell have been distinguished by their dendritic morphology and stratification, but reliable markers for specific ganglion cell populations are still rare. The calcium binding protein calretinin is known to be expressed in the inner nuclear and the ganglion cell layer of marmoset retina, however, the specific cell type(s) expressing calretinin in the ganglion cell layer are yet to be determined. Here, we identified calretinin positive retinal ganglion cells in the common marmoset Callithrix jacchus. Double labeling with the ganglion cell marker RBPMS demonstrated that the large majority (80%) of the calretinin positive cells in the ganglion cell layer are ganglion cells, and 20% are displaced amacrine cells. The calretinin positive ganglion cells made up on average 12% of the total ganglion cell population outside of the foveal region and their proportion increased with eccentricity. Prelabeling with antibodies against calretinin and subsequent intracellular injection with DiI revealed that the large majority of the injected cells (n = 74) were either narrow thorny or broad thorny ganglion cells, 14 cells were displaced amacrine cells. Narrow thorny cells were further distinguished into outer and inner stratifying cells. In addition, weakly labeled cells with a large soma were identified as parasol ganglion cells. Our results show that three types of thorny ganglion cells in marmoset retina can be identified with antibodies against calretinin. Our findings are also consistent with the idea that the proportion of wide-field ganglion cell types increases in peripheral retina. © 2017 Wiley Periodicals, Inc.

  14. Activated retinal glia mediated axon regeneration in experimental glaucoma.

    Science.gov (United States)

    Lorber, Barbara; Guidi, Alessandra; Fawcett, James W; Martin, Keith R

    2012-01-01

    Glaucoma, a leading cause of blindness, is a neurodegenerative disease characterized by progressive loss of retinal ganglion cell axons in the optic nerve and their cell bodies in the retina. Reactive retinal glial changes have been observed in glaucoma but the role of such glial changes in the pathogenesis of the condition remains unclear. In the present study we found that retinal ganglion cells in an experimental animal model of glaucoma have an increased axon regenerative potential. Regeneration of adult rat retinal ganglion cell axons after optic nerve crush was significantly increased in vivo when combined with intraocular pressure-induced experimental glaucoma. This enhanced axon regeneration response was correlated with a significant increase in activation of glial fibrillary acidic protein+retinal glia. Using a dissociated retinal ganglion cell culture model we showed that reducing the number of activated retinal glia with a glial specific toxin, α-Aminoadipic acid, significantly reduced the growth potential of retinal ganglion cells from glaucomatous rat eyes, suggesting that activated retinal glia mediate, at least in part, the growth promoting effect. This was shown to be mediated by both membrane-bound and soluble glial-derived factors. Neurotrophin and ciliary neurotrophic/leukemia inhibitory factor blockers did not affect the regenerative potential, excluding these growth factors as principal mediators of the enhanced growth response occurring in glaucomatous retinal cultures. These observations are the first to reveal that retinal ganglion cells from glaucomatous rat eyes have an enhanced regenerative capacity. Furthermore, our results suggest that activated retinal glia mediate at least part of this response. Further work to understand and enhance the regeneration-promoting effect of activated retinal glia is required to determine if this approach could be useful as part of a therapeutic strategy to encourage optic nerve regeneration in glaucoma

  15. Photovoltaic retinal prosthesis

    Science.gov (United States)

    Loudin, James; Mathieson, Keith; Kamins, Ted; Wang, Lele; Galambos, Ludwig; Huie, Philip; Sher, Alexander; Harris, James; Palanker, Daniel

    2011-03-01

    Electronic retinal prostheses seek to restore sight to patients suffering from retinal degenerative disorders. Implanted electrode arrays apply patterned electrical stimulation to surviving retinal neurons, producing visual sensations. All current designs employ inductively coupled coils to transmit power and/or data to the implant. We present here the design and initial testing of a photovoltaic retinal prosthesis fabricated with a pixel density of up to 177 pixels/mm2. Photodiodes within each pixel of the subretinal array directly convert light to stimulation current, avoiding the use of bulky coil implants, decoding electronics, and wiring, and thereby reducing surgical complexity. A goggles-mounted camera captures the visual scene and transmits the data stream to a pocket processor. The resulting images are projected into the eyes by video goggles using pulsed, near infrared (~900 nm) light. Prostheses with three pixel densities (15, 55, and 177 pix/mm2) are being fabricated, and tests indicate a charge injection limit of 1.62 mC/cm2 at 25Hz. In vitro tests of the photovoltaic retinal stimulation using a 512-element microelectrode array have recorded stimulated spikes from the ganglion cells, with latencies in the 1-100ms range, and with peak irradiance stimulation thresholds varying from 0.1 to 1 mW/mm2. With 1ms pulses at 25Hz the average irradiance is more than 100 times below the IR retinal safety limit. Elicited retinal response disappeared upon the addition of synaptic blockers, indicating that the inner retina is stimulated rather than the ganglion cells directly, and raising hopes that the prosthesis will preserve some of the retina's natural signal processing.

  16. Is the Photoinduced Isomerization in Retinal Protonated Schiff Bases a Single- or Double-Torsional Process?

    Czech Academy of Sciences Publication Activity Database

    Szymczak, J. J.; Barbatti, M.; Lischka, Hans

    2009-01-01

    Roč. 113, č. 43 (2009), s. 11907-11918 ISSN 1089-5639 R&D Projects: GA MŠk LC512 Institutional research plan: CEZ:AV0Z40550506 Keywords : nonadiabatic photodynamical simulations * retinal protonated Schiff base * cis-trans isomerization processes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.899, year: 2009

  17. c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice: a possible target to reduce ganglion cell apoptosis

    Directory of Open Access Journals (Sweden)

    Yue He

    2015-01-01

    Full Text Available Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase (JNK participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by photocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.

  18. The meniscus ganglion

    International Nuclear Information System (INIS)

    Schaefer, H.

    1982-01-01

    Normal dimensions of the meniscus quoted in the literature vary somewhat; measurements were therefore carried out on the height and width on standardised arthrograms. This made it possible to evaluate changes in the height of the meniscus objectively and to diagnose degeneration with a ganglion at an earlier stage. Taking into account other, secondary, signs, 261 meniscus ganglia were diagnosed amongst 3133 meniscus lesions (8.3%) in the course of 5650 knee arthrograms. These were confirmed at operation and histologically. For the first time it has been possible to provide an estimate of the frequency of meniscus ganglion in the radiological literature. (orig.) [de

  19. Spatial distribution of excitatory synapses on the dendrites of ganglion cells in the mouse retina.

    Directory of Open Access Journals (Sweden)

    Yin-Peng Chen

    Full Text Available Excitatory glutamatergic inputs from bipolar cells affect the physiological properties of ganglion cells in the mammalian retina. The spatial distribution of these excitatory synapses on the dendrites of retinal ganglion cells thus may shape their distinct functions. To visualize the spatial pattern of excitatory glutamatergic input into the ganglion cells in the mouse retina, particle-mediated gene transfer of plasmids expressing postsynaptic density 95-green fluorescent fusion protein (PSD95-GFP was used to label the excitatory synapses. Despite wide variation in the size and morphology of the retinal ganglion cells, the expression of PSD95 puncta was found to follow two general rules. Firstly, the PSD95 puncta are regularly spaced, at 1-2 µm intervals, along the dendrites, whereby the presence of an excitatory synapse creates an exclusion zone that rules out the presence of other glutamatergic synaptic inputs. Secondly, the spatial distribution of PSD95 puncta on the dendrites of diverse retinal ganglion cells are similar in that the number of excitatory synapses appears to be less on primary dendrites and to increase to a plateau on higher branch order dendrites. These observations suggest that synaptogenesis is spatially regulated along the dendritic segments and that the number of synaptic contacts is relatively constant beyond the primary dendrites. Interestingly, we also found that the linear puncta density is slightly higher in large cells than in small cells. This may suggest that retinal ganglion cells with a large dendritic field tend to show an increased connectivity of excitatory synapses that makes up for their reduced dendrite density. Mapping the spatial distribution pattern of the excitatory synapses on retinal ganglion cells thus provides explicit structural information that is essential for our understanding of how excitatory glutamatergic inputs shape neuronal responses.

  20. [Observation of single-layered inverted internal limiting membrane flap technique for macular hole with retinal detachment in high myopia].

    Science.gov (United States)

    Xu, C Z; Wu, J H; He, J W; Feng, C

    2017-05-11

    Objective: To compare the outcome of pars plana vitrectomy (PPV) with a single-layered inverted internal limiting membrane (ILM) flap versus PPV with ILM peeling for the treatment of macular hole associated retinal detachment (MHRD) in high myopia. Methods: In a retrospective cohort study, PPV with 2 kinds of adjuvant surgical procedures were used in 35 moderately high myopia eyes with MHRD. These eyes were divided into 2 groups: group 1 (17 eyes) receiving PPV and ILM peeling and group 2 (18 eyes) receiving PPV with a single-layered inverted ILM flap. Anatomical reattachment of the retina, macular hole closure, and best-corrected visual acuity (BCVA) were measured at 6 months after surgery. Results: The retina was successfully reattached in all cases. The difference of the retinal reattachment rate between the two groups was not statistically significant (Fisher's exact test, P= 1.000). The rate of macular hole closure was 47.1% in group 1 (8 eyes) and 88.9% in group 2 (16 eyes). The difference of the macular hole closure rate between the two groups was statistically significant (Fisher's exact test, P= 0.012). Significant improvement in logarithm of minimal angle of resolution (logMAR) BCVA was achieved in both groups. There was no difference in the initial, final, or improved logMAR BCVA in the 2 groups. Conclusion: Single-layered inverted ILM flap technique effectively helps close the macular hole in moderately high myopia with MHRD. This may prevent the possible redetachment from the macular hole. (Chin J Ophthalmol, 2017, 53: 338 - 343) .

  1. High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids

    Science.gov (United States)

    Anderson, David M. G.; Ablonczy, Zsolt; Koutalos, Yiannis; Spraggins, Jeffrey; Crouch, Rosalie K.; Caprioli, Richard M.; Schey, Kevin L.

    2014-01-01

    Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has the ability to provide an enormous amount of information on the abundances and spatial distributions of molecules within biological tissues. The rapid progress in the development of this technology significantly improves our ability to analyze smaller and smaller areas and features within tissues. The mammalian eye has evolved over millions of years to become an essential asset for survival, providing important sensory input of an organism’s surroundings. The highly complex sensory retina of the eye is comprised of numerous cell types organized into specific layers with varying dimensions, the thinnest of which is the 10 μm retinal pigment epithelium (RPE). This single cell layer and the photoreceptor layer contain the complex biochemical machinery required to convert photons of light into electrical signals that are transported to the brain by axons of retinal ganglion cells. Diseases of the retina including age related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy occur when the functions of these cells are interrupted by molecular processes that are not fully understood. In this report, we demonstrate the use of high spatial resolution MALDI IMS and FT-ICR tandem mass spectrometry in the Abca4−/− knockout mouse model of Stargardt disease, a juvenile onset form of macular degeneration. The spatial distributions and identity of lipid and retinoid metabolites are shown to be unique to specific retinal cell layers. PMID:24819461

  2. REDUCED GANGLION CELL VOLUME ON OPTICAL COHERENCE TOMOGRAPHY IN PATIENTS WITH GEOGRAPHIC ATROPHY.

    Science.gov (United States)

    Ramkumar, Hema L; Nguyen, Brian; Bartsch, Dirk-Uwe; Saunders, Luke J; Muftuoglu, Ilkay Kilic; You, Qisheng; Freeman, William R

    2017-11-07

    Geographic atrophy (GA) is the sequelae of macular degeneration. Automated inner retinal analysis using optical coherence tomography is flawed because segmentation software is calibrated for normal eyes. The purpose of this study is to determine whether ganglion cell layer (GCL) volume is reduced in GA using manual analysis. Nineteen eyes with subfoveal GA and 22 controls were selected for morphometric analyses. Heidelberg scanning laser ophthalmoscope optical coherence tomography images of the optic nerve and macula were obtained, and the Viewing Module was used to manually calibrate retinal layer segmentation. Retinal layer volumes in the central 3-mm and surrounding 6-mm diameter were measured. Linear mixed models were used for statistics. The GCL volume in the central 3 mm of the macula is less (P = 0.003), and the retinal nerve fiber layer volume is more (P = 0.02) in patients with GA when compared with controls. Ganglion cell layer volume positively correlated with outer nuclear layer volume (P = 0.020). The patients with geographic atrophy have a small significant loss of the GCL. Ganglion cell death may precede axonal loss, and increased macular retinal nerve fiber layer volumes are not indicative of GCL volume. Residual ganglion cell stimulation by interneurons may enable vision in patients with GA.

  3. Retinitis Pigmentosa

    Science.gov (United States)

    ... is RP inherited? What testing is available? What treatment is available? What is retinitis pigmentosa? Retinitis pigmentosa, also known as RP, refers to a group of inherited diseases causing retinal degeneration. The retina is a thin piece of tissue ...

  4. Cytomegalovirus retinitis

    Science.gov (United States)

    ... sharing features on this page, please enable JavaScript. Cytomegalovirus (CMV) retinitis is a viral infection of the ... need treatment to prevent its return. Alternative Names Cytomegalovirus retinitis Images Eye CMV retinitis CMV (cytomegalovirus) References ...

  5. Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits.

    Science.gov (United States)

    Xu, Hong-Ping; Burbridge, Timothy J; Ye, Meijun; Chen, Minggang; Ge, Xinxin; Zhou, Z Jimmy; Crair, Michael C

    2016-03-30

    Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical,in vitroandin vivoelectrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the "recurrent network" model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic "retinal waves" are initiated in starburst amacrine cells and propagate to retinal ganglion cells

  6. The Ins2Akita mouse as a model of early retinal complications in diabetes.

    Science.gov (United States)

    Barber, Alistair J; Antonetti, David A; Kern, Timothy S; Reiter, Chad E N; Soans, Rohit S; Krady, J Kyle; Levison, Steven W; Gardner, Thomas W; Bronson, Sarah K

    2005-06-01

    This study tested the Ins2(Akita) mouse as an animal model of retinal complications in diabetes. The Ins2(Akita) mutation results in a single amino acid substitution in the insulin 2 gene that causes misfolding of the insulin protein. The mutation arose and is maintained on the C57BL/6J background. Male mice heterozygous for this mutation have progressive loss of beta-cell function, decreased pancreatic beta-cell density, and significant hyperglycemia, as early as 4 weeks of age. Heterozygous Ins2(Akita) mice were bred to C57BL/6J mice, and male offspring were monitored for hyperglycemia, beginning at 4.5 weeks of age. After 4 to 36 weeks of hyperglycemia, the retinas were analyzed for vascular permeability, vascular lesions, leukostasis, morphologic changes of micro- and macroglia, apoptosis, retinal degeneration, and insulin receptor kinase activity. The mean blood glucose of Ins2(Akita) mice was significantly elevated, whereas the body weight at death was reduced compared with that of control animals. Compared with sibling control mice, the Ins2(Akita) mice had increased retinal vascular permeability after 12 weeks of hyperglycemia (P microglia, but no changes in expression of Muller cell glial fibrillary acidic protein. Increased apoptosis was identified by immunoreactivity for active caspase-3 after 4 weeks of hyperglycemia (P cell bodies in the retinal ganglion cell layer (P retinal complications of diabetes.

  7. Development of excitatory and inhibitory neurotransmitters in transitory cholinergic neurons, starburst amacrine cells, and GABAergic amacrine cells of rabbit retina, with implications for previsual and visual development of retinal ganglion cells.

    Science.gov (United States)

    Famiglietti, Edward V; Sundquist, Sarah J

    2010-03-01

    Starburst amacrine cells (SACs), the only acetylcholine (ACh)-releasing amacrine cells (ACs) in adult rabbit retina, contain GABA and are key elements in the retina's directionally selective (DS) mechanism. Unlike many other GABAergic ACs, they use glutamic acid decarboxlyase (GAD)(67), not GAD(65), to synthesize GABA. Using immunocytochemistry, we demonstrate the apoptosis at birth (P0) of transitory putative ACs that exhibit immunoreactivity (IR) for the ACh-synthetic enzyme choline acetyltransferase (ChAT), GAD(67), and the GABA transporter, GAT1. Only a few intact, displaced ChAT-immunoreactive SAC bodies are detected at P0. At P2, ChAT-IR is detected in the two narrowly stratified substrata of starburst dendrites in the inner plexiform layer (IPL). Quantitative analysis reveals that in the first postnatal week, only a small fraction of SACs cells express ChAT- and GABA-IR. Not until the end of the second week are they expressed in all SACs. At P0, a three-tiered stratification of GABA-IR is present in the IPL, entirely different from the adult pattern of seven substrata, emerging at P3-P4, and optimally visualized at P13. At P0, GAD(65) is detectable in normally placed AC bodies. At P1, GAD(65)-IR appears in dendrites of nonstarburst GABAergic ACs, and by P5 is robust in the adult pattern of four substrata in the IPL. GAD(65)-IR never co-localizes with ChAT-IR. In a temporal comparison of our data with physiological, pharmacological, and ultrastructural studies, we suggest that transitory ChAT-immunoreactive cells share with SACs production of stage II (nicotinic) waves of previsual synchronous activity in ganglion cells (GCs). Further, we conclude that (1) GAD(65)-immunoreactive, non-SAC GABAergic ACs are the most likely candidates responsible for the suppression of stage III (muscarinic/AMPA-kainate) waves and (2) DS responses first appear in DS GCs, when about 50% of SACs express ChAT- and GABA-IR, and in 100% of DS GCs, when expression occurs in all SACs.

  8. Axonal transmission in the retina introduces a small dispersion of relative timing in the ganglion cell population response.

    Directory of Open Access Journals (Sweden)

    Günther Zeck

    Full Text Available BACKGROUND: Visual stimuli elicit action potentials in tens of different retinal ganglion cells. Each ganglion cell type responds with a different latency to a given stimulus, thus transforming the high-dimensional input into a temporal neural code. The timing of the first spikes between different retinal projection neurons cells may further change along axonal transmission. The purpose of this study is to investigate if intraretinal conduction velocity leads to a synchronization or dispersion of the population signal leaving the eye. METHODOLOGY/PRINCIPAL FINDINGS: We 'imaged' the initiation and transmission of light-evoked action potentials along individual axons in the rabbit retina at micron-scale resolution using a high-density multi-transistor array. We measured unimodal conduction velocity distributions (1.3±0.3 m/sec, mean ± SD for axonal populations at all retinal eccentricities with the exception of the central part that contains myelinated axons. The velocity variance within each piece of retina is caused by ganglion cell types that show narrower and slightly different average velocity tuning. Ganglion cells of the same type respond with similar latency to spatially homogenous stimuli and conduct with similar velocity. For ganglion cells of different type intraretinal conduction velocity and response latency to flashed stimuli are negatively correlated, indicating that differences in first spike timing increase (up to 10 msec. Similarly, the analysis of pair-wise correlated activity in response to white-noise stimuli reveals that conduction velocity and response latency are negatively correlated. CONCLUSION/SIGNIFICANCE: Intraretinal conduction does not change the relative spike timing between ganglion cells of the same type but increases spike timing differences among ganglion cells of different type. The fastest retinal ganglion cells therefore act as indicators of new stimuli for postsynaptic neurons. The intraretinal dispersion

  9. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    Vugler, Anthony A

    2010-01-01

    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  10. A key role of starburst amacrine cells in originating retinal directional selectivity and optokinetic eye movement.

    Science.gov (United States)

    Yoshida, K; Watanabe, D; Ishikane, H; Tachibana, M; Pastan, I; Nakanishi, S

    2001-06-01

    The directional selectivity of retinal ganglion cell responses represents a primitive pattern recognition that operates within a retinal neural circuit. The cellular origin and mechanism of directional selectivity were investigated by selectively eliminating retinal starburst amacrine cells, using immunotoxin-mediated cell targeting techniques. Starburst cell ablation in the adult retina abolished not only directional selectivity of ganglion cell responses but also an optokinetic eye reflex derived by stimulus movement. Starburst cells therefore serve as the key element that discriminates the direction of stimulus movement through integrative synaptic transmission and play a pivotal role in information processing that stabilizes image motion.

  11. Studies of retinal representations within the cat's optic tract

    International Nuclear Information System (INIS)

    Torrealba, F.; Guillery, R.W.; Eysel, U.; Polley, E.H.; Mason, C.A.

    1982-01-01

    The manner in which each retina can be mapped onto a single cross section of the optic tract of the cat has been defined by neuroanatomical methods. It has been found that the contralateral nasal hemi-retina and both temporal hemi-retinae are represented in each tract by multiple, rough maps which partially overlap one another. All maps show the same general orientation, with area centralis represented dorsomedially, lower retina represented dorsolaterally, and upper retina represented ventromedially. The peripheral part of the horizontal meridian is represented ventrolaterally. Labeling all of the fibers from one eye by axonal degeneration or autoradiographic methods shows that the crossed map is displaced dorsally and medially relative to the uncrossed map, leaving a dorsomedial crescent of pure crossed fibers. Localized retinal lesions or injections of 3 H-amino acid show the general orientation of the maps. Lesions within the dorsomedial pure crossed crescent show that fibers in this crescent arise from retinal areas close to the optic disc, near the site of the early fetal fissure. Localized injections of horseradish peroxidase into the optic tract show the relationships of the several maps in terms of the retinal distribution of retrogradely labeled retinal ganglion cells. They show that axons of large and small cells map ventrolaterally in the tract while intermediate sizes map dorsomedially. They confirm that the crossed map is displaced relative to the uncrossed maps. It is suggested that the optic tract develops by fibers taking a position in the tract in accordance with their time of arrival at the chiasm. The several maps are displaced because they develop sequentially and the optic tract can be read as a developmental record, the most dorsomedial axons being the oldest

  12. Retinal Vasculitis

    Science.gov (United States)

    Rosenbaum, James T.; Sibley, Cailin H.; Lin, Phoebe

    2016-01-01

    Purpose of review Ophthalmologists and rheumatologists frequently miscommunicate in consulting on patients with retinal vasculitis. This report seeks to establish a common understanding of the term, retinal vasculitis, and to review recent papers on this diagnosis. Recent findings 1) The genetic basis of some rare forms of retinal vascular disease have recently been described. Identified genes include CAPN5, TREX1, and TNFAIP3; 2) Behçet’s disease is a systemic illness that is very commonly associated with occlusive retinal vasculitis; 3) retinal imaging including fluorescein angiography and other newer imaging modalities has proven crucial to the identification and characterization of retinal vasculitis and its complications; 4) although monoclonal antibodies to IL-17A or IL-1 beta failed in trials for Behçet’s disease, antibodies to TNF alpha, either infliximab or adalimumab, have demonstrated consistent benefit in managing this disease. Interferon treatment and B cell depletion therapy via rituximab may be beneficial in certain types of retinal vasculitis. Summary Retinal vasculitis is an important entity for rheumatologists to understand. Retinal vasculitis associated with Behçet’s disease responds to monoclonal antibodies that neutralize TNF, but the many other forms of non-infectious retinal vasculitis may require alternate therapeutic management. PMID:26945335

  13. Anatomical Analysis of the Retinal Specializations to a Crypto-Benthic, Micro-Predatory Lifestyle in the Mediterranean Triplefin Blenny Tripterygion delaisi

    Directory of Open Access Journals (Sweden)

    Roland Fritsch

    2017-12-01

    Full Text Available The environment and lifestyle of a species are known to exert selective pressure on the visual system, often demonstrating a tight link between visual morphology and ecology. Many studies have predicted the visual requirements of a species by examining the anatomical features of the eye. However, among the vast number of studies on visual specializations in aquatic animals, only a few have focused on small benthic fishes that occupy a heterogeneous and spatially complex visual environment. This study investigates the general retinal anatomy including the topography of both the photoreceptor and ganglion cell populations and estimates the spatial resolving power (SRP of the eye of the Mediterranean triplefin Tripterygion delaisi. Retinal wholemounts were prepared to systematically and quantitatively analyze photoreceptor and retinal ganglion cell (RGC densities using design-based stereology. To further examine the retinal structure, we also used magnetic resonance imaging (MRI and histological examination of retinal cross sections. Observations of the triplefin’s eyes revealed them to be highly mobile, allowing them to view the surroundings without body movements. A rostral aphakic gap and the elliptical shape of the eye extend its visual field rostrally and allow for a rostro-caudal accommodatory axis, enabling this species to focus on prey at close range. Single and twin cones dominate the retina and are consistently arranged in one of two regular patterns, which may enhance motion detection and color vision. The retina features a prominent, dorso-temporal, convexiclivate fovea with an average density of 104,400 double and 30,800 single cones per mm2, and 81,000 RGCs per mm2. Based on photoreceptor spacing, SRP was calculated to be between 6.7 and 9.0 cycles per degree. Location and resolving power of the fovea would benefit the detection and identification of small prey in the lower frontal region of the visual field.

  14. Retinal vasculitis.

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; Herbort, Carl P; Tabbara, Khalid F

    2005-12-01

    Retinal vasculitis is a sight-threatening intraocular inflammation affecting the retinal vessels. It may occur as an isolated ocular condition, as a manifestation of infectious or neoplastic disorders, or in association with a systemic inflammatory disease. The search for an underlying etiology should be approached in a multidisciplinary fashion based on a thorough history, review of systems, physical examination, and laboratory evaluation. Discrimination between infectious and noninfectious etiologies of retinal vasculitis is important because their treatment is different. This review is based on recently published articles on retinal vasculitis and deals with its clinical diagnosis, its link with systemic diseases, and its laboratory investigation.

  15. The RNA binding protein RBPMS is a selective marker of ganglion cells in the mammalian retina

    Science.gov (United States)

    Rodriguez, Allen R.; de Sevilla Müller, Luis Pérez; Brecha, Nicholas C.

    2014-01-01

    There are few neurochemical markers that reliably identify retinal ganglion cells (RGCs), which are a heterogeneous population of cells that integrate and transmit the visual signal from the retina to the central visual nuclei. We have developed and characterized a new set of affinity purified guinea pig and rabbit antibodies against RNA-binding protein with multiple splicing (RBPMS). On Western blots these antibodies recognize a single band at ~24 kDa, corresponding to RBPMS, and they strongly label RGC and displaced RGC (dRGC) somata in mouse, rat, guinea pig, rabbit and monkey retina. RBPMS immunoreactive cells and RGCs identified by other techniques have a similar range of somal diameters and areas. The density of RBPMS cells in mouse and rat retina is comparable to earlier semi-quantitative estimates of RGCs. RBPMS is mainly expressed in medium and large DAPI-, DRAQ5-, NeuroTrace- and NeuN-stained cells in the ganglion cell layer (GCL), and RBPMS is not expressed in syntaxin (HPC-1) immunoreactive cells in the inner nuclear layer (INL) and GCL, consistent with their identity as RGCs, and not displaced amacrine cells. In mouse and rat retina, most RBPMS cells are lost following optic nerve crush or transection at three weeks, and all Brn3a, SMI-32 and melanopsin immunoreactive RGCs also express RBPMS immunoreactivity. RBPMS immunoreactivity is localized to CFP-fluorescent RGCs in the B6.Cg-Tg(Thy1-CFP)23Jrs/J mouse line. These findings show that antibodies against RBPMS are robust reagents that exclusively identify RGCs and dRGCs in multiple mammalian species, and they will be especially useful for quantification of RGCs. PMID:24318667

  16. Retinal Detachment

    Science.gov (United States)

    ... specific questions. Retinal Detachment Defined What is retinal detachment? The retina is the light-sensitive layer of tissue that ... the most common. Tractional —In this type of detachment, scar tissue on the retina’s surface contracts and causes the retina to separate ...

  17. Retinal meteor.

    Science.gov (United States)

    Venkatesh, Ramesh; Gurav, Prachi; Dave, Prachi Abhishek; Roy, Sankhadeep

    2017-09-01

    We describe a case of a 65-year old man diagnosed with retinal vasoproliferative tumour secondary to posterior uveitis. The fluorescein angiography shows an interesting meteor-like leak emanating from the tumour and rising towards the superior retina in the later frames of the angiogram. Pictorially, we call it the "Retinal Meteor" and also describe the possible mechanism for this pattern of leakage.

  18. Biophysical Variation within the M1 Type of Ganglion Cell Photoreceptor

    Directory of Open Access Journals (Sweden)

    Alan J. Emanuel

    2017-10-01

    Full Text Available Intrinsically photosensitive retinal ganglion cells of the M1 type encode environmental irradiance for functions that include circadian and pupillary regulation. Their distinct role, morphology, and molecular markers indicate that they are stereotyped circuit elements, but their physiological uniformity has not been investigated in a systematic fashion. We have profiled the biophysical parameters of mouse M1s and found that extreme variation is their hallmark. Most parameters span 1–3 log units, and the full range is evident in M1s that innervate brain regions serving divergent functions. Biophysical profiles differ among cells possessing similar morphology and between neighboring M1s recorded simultaneously. Variation in each parameter is largely independent of that in others, allowing for flexible individualization. Accordingly, a common stimulus drives heterogeneous spike outputs across cells. By contrast, a population of directionally selective retinal ganglion cells appeared physiologically uniform under similar conditions. Thus, M1s lack biophysical constancy and send diverse signals downstream.

  19. Mechanisms of Retinal Damage after Ocular Alkali Burns.

    Science.gov (United States)

    Paschalis, Eleftherios I; Zhou, Chengxin; Lei, Fengyang; Scott, Nathan; Kapoulea, Vassiliki; Robert, Marie-Claude; Vavvas, Demetrios; Dana, Reza; Chodosh, James; Dohlman, Claes H

    2017-06-01

    Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors. Tissue inflammation was assessed by immunohistochemistry and flow cytometry. The experiments confirmed that the retinal damage is not mediated by direct effect of the alkali, which is effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation reduction changes were restricted to the cornea and the anterior chamber, where they caused profound uveal inflammation and release of proinflammatory cytokines. The latter rapidly diffuse to the posterior segment, triggering retinal damage. Tumor necrosis factor-α was identified as a key proinflammatory mediator of retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion cell loss. Intraocular pressure elevation was not observed in experimental alkali burns. These findings illuminate the mechanism by which alkali burns cause retinal damage and may have importance in designing therapies for retinal protection. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Effects of phenolic acid metabolites formed after chlorogenic acid consumption on retinal degeneration in vivo.

    Science.gov (United States)

    Jang, Holim; Choi, Yongsoo; Ahn, Hong Ryul; Jung, Sang Hoon; Lee, Chang Yong

    2015-10-01

    Although ingestion of coffee and its constituent chlorogenic acid (CGA) protects the retina from oxidative stress, the bioaccessibility and bioavailability of coffee metabolites are not well understood. The aim of this study was to determine which coffee metabolites reach the retina and protect against retinal degeneration. UPLC-MS/MS was used to detect CGA and coffee metabolites in the rat eye. The methyl thiazolyl tetrazolium assay and double staining with Hoechst and propidium iodide showed that CGA, caffeic acid (CA), and dihydrocaffeic acid (DHCA) protect retinal ganglion cells from hypoxia-induced damage. Western blots showed that treatment with coffee metabolites up-regulated anti-apoptotic proteins such as Bcl-2 and Bcl-XL and down-regulated pro-apoptotic proteins such as Bad, PARP, and cleaved caspase 3. Adult ICR mice were subjected to optic nerve crush-induced retinal ganglion cell death with intravitreal pre-treatment with coffee metabolites 1 day before and 1 h after the procedure. Retrograde Fluorogold(TM) labeling showed severe retinal ganglion cell loss after optic nerve crushing, and coffee metabolites significantly reduced damage to retinal ganglion cells. CGA and coffee metabolites, especially, CA, and DHCA, reach the eye, where they can significantly reduce apoptosis induced by hypoxia and optic nerve crush stress, and thus prevent retinal degeneration. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Retinal origin of direction selectivity in the superior colliculus.

    Science.gov (United States)

    Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron; Koren, David; Jin, Yanjiao; Liu, Xiaorong; Wei, Wei; Cang, Jianhua

    2017-04-01

    Detecting visual features in the environment, such as motion direction, is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. We optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly tuned retinal ganglion cells. The direction-selective retinal input is linearly amplified by intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using two-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC and reveal a central visual deficit as a consequence of altered feature selectivity in the retina.

  2. Chaetomium retinitis.

    Science.gov (United States)

    Tabbara, Khalid F; Wedin, Keith; Al Haddab, Saad

    2010-01-01

    To report a case of Chaetomium atrobrunneum retinitis in a patient with Hodgkin lymphoma. We studied the ocular manifestations of an 11-year-old boy with retinitis. Biomicroscopy, ophthalmoscopy, and fundus photography were done. Magnetic resonance imaging of the brain was performed. A vitreous biopsy was subjected to viral, bacterial, and fungal cultures. Vitreous culture grew C. atrobrunneum. Magnetic resonance imaging showed multiple cerebral lesions consistent with an infectious process. The patient was given intravenous voriconazole and showed improvement of the ocular and central nervous system lesions. We report a case of central nervous system and ocular lesions by C. atrobrunneum. The retinitis was initially misdiagnosed as cytomegaloviral retinitis. Vitreous biopsy helped in the early diagnosis and prompt treatment of a life- and vision-threatening infection.

  3. Retinal Detachment Vision Simulator

    Science.gov (United States)

    ... What Is a Torn or Detached Retina? Retinal Detachment: Torn or Detached Retina Causes Retinal Detachment: Who Is At Risk for a Torn or Detached Retina? Retinal Detachment: Torn or Detached Retina Symptoms Retinal Detachment: Torn or Detached Retina Diagnosis ...

  4. Sphenopalatine ganglion neuromodulation in migraine

    DEFF Research Database (Denmark)

    Khan, Sabrina; Schoenen, Jean; Ashina, Messoud

    2014-01-01

    OBJECTIVE: The objective of this article is to review the prospect of treating migraine with sphenopalatine ganglion (SPG) neurostimulation. BACKGROUND: Fuelled by preliminary studies showing a beneficial effect in cluster headache patients, the potential of treating migraine with neurostimulation...... has gained increasing interest within recent years, as current treatment strategies often fail to provide adequate relief from this debilitating headache. Common migraine symptoms include lacrimation, nasal congestion, and conjunctival injection, all parasympathetic manifestations. In addition......, studies have suggested that parasympathetic activity may also contribute to the pain of migraineurs. The SPG is the largest extracranial parasympathetic ganglion of the head, innervating the meninges, lacrimal gland, nasal mucosa, and conjunctiva, all structures involved in migraine with cephalic...

  5. Stratification of alpha ganglion cells and ON/OFF directionally selective ganglion cells in the rabbit retina

    OpenAIRE

    ZHANG, JIAN; LI, WEI; HOSHI, HIDEO; MILLS, STEPHEN L.; MASSEY, STEPHEN C.

    2005-01-01

    The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF α ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF α ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sens...

  6. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

    Energy Technology Data Exchange (ETDEWEB)

    Do, Ji Yeon; Choi, Young Keun [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kook, Hyun [Department of Pharmacology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Lee, In-Kyu [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Park, Dong Ho, E-mail: sarasate2222@gmail.com [Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2015-05-01

    Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O{sub 2}). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice.

  7. Retinal Remodeling: Concerns, Emerging Remedies, and Future Prospects

    Directory of Open Access Journals (Sweden)

    Vidhyasankar eKrishnamoorthy

    2016-02-01

    Full Text Available Deafferentation results not only in sensory loss, but also in a variety of alterations in the postsynaptic circuitry. These alterations may have detrimental impact on potential treatment strategies. Progressive loss of photoreceptors in retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, leads to several changes in the remnant retinal circuitry. Müller glial cells undergo hypertrophy and form a glial seal. The second- and third-order retinal neurons undergo morphological, biochemical and physiological alterations. A result of these alterations is that retinal ganglion cells (RGCs, the output neurons of the retina, become hyperactive and exhibit spontaneous, oscillatory bursts of spikes. This aberrant electrical activity degrades the signal-to-noise ratio in RGC responses, and thus the quality of information they transmit to the brain. These changes in the remnant retina, collectively termed retinal remodeling, pose challenges for genetic, cellular and bionic approaches to restore vision. It is therefore crucial to understand the nature of retinal remodeling, how it affects the ability of remnant retina to respond to novel therapeutic strategies, and how to ameliorate its effects. In this article, we discuss these topics, and suggest that the pathological state of the retinal output following photoreceptor loss is reversible, and therefore, amenable to restorative strategies.

  8. Retinal Remodeling: Concerns, Emerging Remedies and Future Prospects.

    Science.gov (United States)

    Krishnamoorthy, Vidhyasankar; Cherukuri, Pitchaiah; Poria, Deepak; Goel, Manvi; Dagar, Sushma; Dhingra, Narender K

    2016-01-01

    Deafferentation results not only in sensory loss, but also in a variety of alterations in the postsynaptic circuitry. These alterations may have detrimental impact on potential treatment strategies. Progressive loss of photoreceptors in retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, leads to several changes in the remnant retinal circuitry. Müller glial cells undergo hypertrophy and form a glial seal. The second- and third-order retinal neurons undergo morphological, biochemical and physiological alterations. A result of these alterations is that retinal ganglion cells (RGCs), the output neurons of the retina, become hyperactive and exhibit spontaneous, oscillatory bursts of spikes. This aberrant electrical activity degrades the signal-to-noise ratio in RGC responses, and thus the quality of information they transmit to the brain. These changes in the remnant retina, collectively termed "retinal remodeling", pose challenges for genetic, cellular and bionic approaches to restore vision. It is therefore crucial to understand the nature of retinal remodeling, how it affects the ability of remnant retina to respond to novel therapeutic strategies, and how to ameliorate its effects. In this article, we discuss these topics, and suggest that the pathological state of the retinal output following photoreceptor loss is reversible, and therefore, amenable to restorative strategies.

  9. Retinal Vascular Fractals Correlate With Early Neurodegeneration in Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Frydkjaer-Olsen, Ulrik; Soegaard Hansen, Rasmus; Pedersen, Knud; Peto, Tunde; Grauslund, Jakob

    2015-11-01

    To investigate the correlation between the retinal vascular fractal dimension (Fd) and neurodegenerative changes in patients with no or mild diabetic retinopathy (DR). In this cross-sectional study we examined 103 patients with type 2 diabetes mellitus (T2DM) with no or mild DR. In a randomly selected eye of each patient, Fd was calculated using SIVA-Fractal, a specialized semiautomatic software. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral-domain optical coherence tomography (OCT) and by a RETI-scan multifocal ERG (mf-ERG) system in rings one to six. Level of DR was determined by a single trained grader in seven-field fundus photos according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Mean age and duration of T2DM were 62.3 and 11.6 years, respectively; 46.6% were men. Mean Fd was 1.413 (range, 1.278-1.509) and ETDRS levels were 10 (42.7%), 20 (35.0%), and 35 (22.3%), respectively. Fd correlated inversely with mf-ERG implicit time of ring one (r = -0.25, P = 0.01) and present diabetic neuropathy (P = 0.02), and positively with OCT ganglion cell layer (GCL) thickness (r = 0.20, P = 0.04). In a multivariable linear regression model, Fd was associated with mf-ERG implicit time of ring one (coefficient -0.0021/ms, P = 0.040) and the presence of diabetic neuropathy (coefficient -0.0209 for neuropathy present versus absent, P = 0.041). In patients with T2DM and no or minimal DR, independent correlations were found between early vascular and neurogenic changes. Thus, retinal vascular fractal analysis might be considered as a tool to identify patients with early neurodegenerative retinal changes.

  10. SUPRACHOROIDAL BUCKLING FOR THE MANAGEMENT OF RHEGMATOGENOUS RETINAL DETACHMENTS SECONDARY TO PERIPHERAL RETINAL BREAKS.

    Science.gov (United States)

    El Rayes, Ehab N; Mikhail, Mikel; El Cheweiky, Hala; Elsawah, Kareem; Maia, Andre

    2017-04-01

    To evaluate functional and anatomical outcomes of eyes undergoing suprachoroidal buckling for the management of peripheral retinal breaks in rhegmatogenous retinal detachment. Retrospective cohort study of 41 eyes of 41 patients undergoing suprachoroidal buckling for the management of rhegmatogenous retinal detachment secondary to single or multiple retinal breaks. Suprachoroidal indentation was achieved through the introduction of filler material using a 23-gauge (23-G) olive-tipped, suprachoroidal cannula. This allowed for the creation of a suprachoroidal dome and chorio-retinal apposition. Healon5 (Abbott Medical Optics) was used as filler material in all eyes. Combined 25-G vitrectomy was performed in 5 eyes. Cryopexy and laserpexy were used in 37 and 4 eyes, respectively. Mean visual acuity gain was the primary outcome measure. Final retinal reattachment rate, single-surgery reattachment rate, and complications were secondary outcome measures. Mean best-corrected distance visual acuity improved from 20/1,100 to 20/42. Single surgery reattachment rate was 92.7% (38/41 eyes). Final retinal reattachment was achieved in all 41 eyes (100%). There was no statistically significant difference in visual acuity gain or anatomical reattachment in terms of retinal break quadrant or extent. No major complications were observed. Two localized suprachoroidal hemorrhages occurred at the entry site for the cannula. These resolved without further intervention. Suprachoroidal buckling using a specially designed cannula is a safe and effective procedure for the management of rhegmatogenous retinal detachment secondary to peripheral retinal breaks.

  11. Retinal Detachment

    Directory of Open Access Journals (Sweden)

    Adnan Riaz, MD

    2018-04-01

    Full Text Available History of present illness: A 58-year-old female presented to the emergency department reporting six days of progressive, atraumatic left eye vision loss. Her symptoms started with the appearance of dark spots and “spider webs,” and then progressed to darkening of vision in her left eye. She reports mild pain since yesterday. Her review of symptoms was otherwise negative. Ocular physical examination revealed normal external appearance, intact extraocular movements, and visual acuities of 20/25 OD and light/dark sensitivity OS. Fluorescein uptake was negative and slit lamp exam was unremarkable. Significant findings: Bedside ocular ultrasound revealed a serpentine, hyperechoic membrane that appeared tethered to the optic disc posteriorly with hyperechoic material underneath. These findings are consistent with retinal detachment (RD and associated retinal hemorrhage. Discussion: The retina is a layer of organized neurons that line the posterior portion of the posterior chamber of the eye. RD occurs when this layer separates from the underlying epithelium, resulting in ischemia and progressive photoreceptor degeneration, with potentially rapid and permanent vision loss if left untreated.1 Risk factors include advanced age, male sex (60%, race (Asians and Jews, and myopia and lattice degeneration.2 Bedside ultrasound (US performed by emergency physicians provides a valuable tool that has been used by ophthalmologists for decades to evaluate intraocular disease.1,3 Findings on bedside ultrasound consistent with RD include a hyperechoic membrane floating in the posterior chamber. RD usuallyremain tethered to the optic disc posteriorly and do not cross midline, a feature distinguishing them from posterior vitreous detachments. Associated retinal hemorrhage, seen as hyperechoic material under the retinal flap, can often be seen.1,2 US can also distinguish between “mac-on” and “mac-off” detachments. If the retina is still attached to the

  12. The pterygopalatine ganglion in humans: a morphological study.

    Science.gov (United States)

    Rusu, M C; Pop, F; Curcă, G C; Podoleanu, L; Voinea, L M

    2009-04-01

    As a rule the pterygopalatine ganglion (PPG) is considered to be a single structure of the parasympathetic nervous system, associated with the maxillary nerve in the pterygopalatine fossa (PPF). A few structural studies in humans are available in the indexed references. We designed the present study of the PPG in order to provide evidence of possible variations in morphological patterns of the PPG. We performed dissections of the PPF on 20 human adult heads, using different approaches. The dissected specimens were stained with hematoxylin-eosin and silver (Bielschowsky) or prepared for immunohistochemistry for synaptophisin and neurofilament. Four morphological types of the PPG were defined macroscopically: A (10%): partitioned PPG, the upper partition receiving the vidian nerve; B (55%): single, the upper part (base) receiving the vidian nerve; C (15%): single, but the vidian nerve reaches the lower part (tip) of the ganglion; D (20%): partitioned, the lower partition receiving the vidian nerve. We propose that it may be inappropriate to invariably regard the PPG as a single morphological structure. From individual to individual the PPG may present either as a single ganglion or as a partitioned one, with distinct superior and inferior components. Nevertheless, the presence of the dispersed pterygopalatine microganglia (DPPG) evidenced by histochemistry and immunohistochemistry serves to complete an individually variable morphological pattern of a structure usually described as single. The individual variation may be the reason for failures in ablation procedures of the PPG; partitions of the PPG and/or the DPPG may functionally correlate with specific territories and targets and further tracing studies may be helpful in validating or invalidating this theory.

  13. Sentinel Ganglions in Malignant Tumors of the Oral Cavity

    International Nuclear Information System (INIS)

    Cambrea, M.; Vlad, D.; Hincu, Mihaela; Sivoglo, V.

    2006-01-01

    Full text: Objectives: The use of lymphoscintigraphy in order to show lymphatic invasion, for a better precision of the surgical act as well as for the delimitation of the volumes-target to settle the radio therapeutic treatment. Material And Method: A group of 20 patients (18 men and 2 women) diagnosed with malign tumors of the oral cavity with no clinical adenopathy (N0), investigated clinically and para clinically (laboratory examinations and lymphoscintigraphy associated with bone scintigraphy). The lymphoscintigraphy was performed by the pritumoral injection of 18.5MBq 99m Tc-Nanocoll in 4 points. Before the lymphoscintigraphy was performed each patient had been injected with 750MBq Medronat. The images were taken with a GE eNTEGRA 2.5202. system. Pre-operatory (20 min.) intra vital coloring was performed with metilen blue by peritumoral injection. The surgery addressed to the primary tumor was completed by a supraomohioidian cervical vacuuming. Results: The lymphoscintigraphy showed the lymphatic drain of the malign tumors in 95% of the cases. All malign tumors of the oral cavity drain in the latero-cervical lymphatic ganglions (bilateral), most frequently the sentinel ganglions being found at the level IIb (48%), followed by level III (32%), level I-a (16%) and others (4%).The identification of the lymphatic ganglions pre-operatory by inter vital coloration was of 90.62%. The morphology of the satellite lymphoganglions is closely related to the histological type and the degree of differentiation of the tumors. In the invasive forms the frequency of the nodal metastases varies with the clinical stage of the tumor. In a single case multiple bone metastases were found by scintigraphy fact that led to the change of therapeutic attitude. Conclusions: Lymphoscintigraphy is essential for the settling of the therapeutic attitude towards the malign tumors of the oral cavity, due to: - the early detection of the invaded lymphatic ganglions (83 sentinel ganglions found

  14. Retinitis pigmentosa

    Directory of Open Access Journals (Sweden)

    Hamel Christian

    2006-10-01

    Full Text Available Abstract Retinitis pigmentosa (RP is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms. Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema, and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis.

  15. Head-to-head comparison of ranibizumab PRN versus single-dose dexamethasone for branch retinal vein occlusion (COMRADE-B).

    Science.gov (United States)

    Hattenbach, Lars-Olof; Feltgen, Nicolas; Bertelmann, Thomas; Schmitz-Valckenberg, Steffen; Berk, Hüsnü; Eter, Nicole; Lang, Gabriele E; Rehak, Matus; Taylor, Simon R; Wolf, Armin; Weiss, Claudia; Paulus, Eva-Maria; Pielen, Amelie; Hoerauf, Hans

    2018-02-01

    To compare the efficacy and safety of ranibizumab 0.5 mg versus dexamethasone 0.7 mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. Patients received either monthly ranibizumab for 3 months followed by Pro re nata (PRN) treatment (n = 126) or a sustained-release dexamethasone implant followed by PRN sham injections (n = 118). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean changes in BCVA and foveal centre point thickness (FCPT), and adverse events (AEs). There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 (±11) letters versus +9.3 (±10.1) letters]. At month 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  16. Paracoccygeal corkscrew approach to ganglion impar injections for tailbone pain.

    Science.gov (United States)

    Foye, Patrick M; Patel, Shounuck I

    2009-01-01

    A new technique for performing nerve blocks of the ganglion impar (ganglion Walther) is presented. These injections have been reported to relieve coccydynia (tailbone pain), as well as other malignant and nonmalignant pelvic pain syndromes. A variety of techniques have been previously described for blocking this sympathetic nerve ganglion, which is located in the retrorectal space just anterior to the upper coccygeal segments. Prior techniques have included approaches through the anococcygeal ligament, through the sacrococcygeal joint, and through intracoccygeal joint spaces. This article presents a new, paracoccygeal approach whereby the needle is inserted alongside the coccyx and the needle is guided through three discrete steps with a rotating or corkscrew trajectory. Compared with some of the previously published techniques, this paracoccygeal corkscrew approach has multiple potential benefits, including ease of fluoroscopic guidance using the lateral view, ability to easily use a stylet for the spinal needle, and use of a shorter, thinner needle. While no single technique works best for all patients and each technique has potential advantages and disadvantages, this new technique adds to the available options.

  17. Caudal mesenteric ganglion in the sheep - macroanatomical and immunohistochemical study.

    Science.gov (United States)

    Sienkiewicz, W; Chrószcz, A; Dudek, A; Janeczek, M; Kaleczyc, J

    2015-01-01

    The caudal mesenteric ganglion (CaMG) is a prevetrebral ganglion which provides innervation to a number of organs in the abdominal and pelvic cavity. The morphology of CaMG and the chemical coding of neurones in this ganglion have been described in humans and many animal species, but data on this topic in the sheep are entirely lacking. This prompted us to undertake a study to determine the localization and morphology of sheep CaMG as well as immunohistochemical properties of its neurons. The study was carried out on 8 adult sheep, weighing from 40 to 60 kg each. The sheep were deeply anaesthetised and transcardially perfused with 4% paraformaldehyde. CaMG-s were exposed and their location was determined. Macroanatomical observations have revealed that the ovine CaMG is located at the level of last two lumbar (L5 or L6) and the first sacral (S1) vertebrae. The ganglion represents an unpaired structure composed of several, sequentially arranged aggregates of neurons. Immunohistochemical investigations revealed that nearly all (99.5%) the neurons were DβH-IR and were richly supplied by VACHT-IR nerve terminals forming "basket-like" structures around the perikarya. VACHT-IR neurones were not determined. Many neurons (55%) contained immunoreactivity to NPY, some of them (10%) stained for Met-ENK and solitary nerve cells were GAL-positive. CGRP-IR nerve fibres were numerous and a large number of them simultaneously expressed immunoreactivity to SP. Single, weakly stained neurones were SP-IR and only very few nerve cells weakly stained for VIP.

  18. Suppressed retinal degeneration in aged wild type and APPswe/PS1ΔE9 mice by bone marrow transplantation.

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    Yue Yang

    Full Text Available Alzheimer's disease (AD is an age-related condition characterized by accumulation of neurotoxic amyloid β peptides (Aβ in brain and retina. Because bone marrow transplantation (BMT results in decreased cerebral Aβ in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal Aβ. To test this, we performed BMT in APPswe/PS1ΔE9 double transgenic mice using green fluorescent protein expressing wild type (wt mice as marrow donors. We first examined retinas from control, non-transplanted, aged AD mice and found a two-fold increase in microglia compared with wt mice, prominent inner retinal Aβ and paired helical filament-tau, and decreased retinal ganglion cell layer neurons. BMT resulted in near complete replacement of host retinal microglia with BMT-derived cells and normalized total AD retinal microglia to non-transplanted wt levels. Aβ and paired helical filament-tau were reduced (61.0% and 44.1% respectively in BMT-recipient AD mice, which had 20.8% more retinal ganglion cell layer neurons than non-transplanted AD controls. Interestingly, aged wt BMT recipients also had significantly more neurons (25.4% compared with non-transplanted aged wt controls. Quantitation of retinal ganglion cell layer neurons in young mice confirmed age-related retinal degeneration was mitigated by BMT. We found increased MHC class II expression in BMT-derived microglia and decreased oxidative damage in retinal ganglion cell layer neurons. Thus, BMT is neuroprotective in age-related as well as AD-related retinal degeneration, and may be a result of alterations in innate immune function and oxidative stress in BMT recipient mice.

  19. Random Wiring, Ganglion Cell Mosaics, and the Functional Architecture of the Visual Cortex.

    Science.gov (United States)

    Schottdorf, Manuel; Keil, Wolfgang; Coppola, David; White, Leonard E; Wolf, Fred

    2015-11-01

    The architecture of iso-orientation domains in the primary visual cortex (V1) of placental carnivores and primates apparently follows species invariant quantitative laws. Dynamical optimization models assuming that neurons coordinate their stimulus preferences throughout cortical circuits linking millions of cells specifically predict these invariants. This might indicate that V1's intrinsic connectome and its functional architecture adhere to a single optimization principle with high precision and robustness. To validate this hypothesis, it is critical to closely examine the quantitative predictions of alternative candidate theories. Random feedforward wiring within the retino-cortical pathway represents a conceptually appealing alternative to dynamical circuit optimization because random dimension-expanding projections are believed to generically exhibit computationally favorable properties for stimulus representations. Here, we ask whether the quantitative invariants of V1 architecture can be explained as a generic emergent property of random wiring. We generalize and examine the stochastic wiring model proposed by Ringach and coworkers, in which iso-orientation domains in the visual cortex arise through random feedforward connections between semi-regular mosaics of retinal ganglion cells (RGCs) and visual cortical neurons. We derive closed-form expressions for cortical receptive fields and domain layouts predicted by the model for perfectly hexagonal RGC mosaics. Including spatial disorder in the RGC positions considerably changes the domain layout properties as a function of disorder parameters such as position scatter and its correlations across the retina. However, independent of parameter choice, we find that the model predictions substantially deviate from the layout laws of iso-orientation domains observed experimentally. Considering random wiring with the currently most realistic model of RGC mosaic layouts, a pairwise interacting point process, the

  20. Random Wiring, Ganglion Cell Mosaics, and the Functional Architecture of the Visual Cortex.

    Directory of Open Access Journals (Sweden)

    Manuel Schottdorf

    2015-11-01

    Full Text Available The architecture of iso-orientation domains in the primary visual cortex (V1 of placental carnivores and primates apparently follows species invariant quantitative laws. Dynamical optimization models assuming that neurons coordinate their stimulus preferences throughout cortical circuits linking millions of cells specifically predict these invariants. This might indicate that V1's intrinsic connectome and its functional architecture adhere to a single optimization principle with high precision and robustness. To validate this hypothesis, it is critical to closely examine the quantitative predictions of alternative candidate theories. Random feedforward wiring within the retino-cortical pathway represents a conceptually appealing alternative to dynamical circuit optimization because random dimension-expanding projections are believed to generically exhibit computationally favorable properties for stimulus representations. Here, we ask whether the quantitative invariants of V1 architecture can be explained as a generic emergent property of random wiring. We generalize and examine the stochastic wiring model proposed by Ringach and coworkers, in which iso-orientation domains in the visual cortex arise through random feedforward connections between semi-regular mosaics of retinal ganglion cells (RGCs and visual cortical neurons. We derive closed-form expressions for cortical receptive fields and domain layouts predicted by the model for perfectly hexagonal RGC mosaics. Including spatial disorder in the RGC positions considerably changes the domain layout properties as a function of disorder parameters such as position scatter and its correlations across the retina. However, independent of parameter choice, we find that the model predictions substantially deviate from the layout laws of iso-orientation domains observed experimentally. Considering random wiring with the currently most realistic model of RGC mosaic layouts, a pairwise interacting point

  1. Establishing an experimental rat model of photodynamically-induced retinal vein occlusion using erythrosin B

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    Wei Chen

    2014-04-01

    Full Text Available AIM:To develop a reliable, reproducible rat model of retinal vein occlusion (RVO with a novel photosensitizer (erythrosin B and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia. Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h, and 1, 4, 7, 14, and 21d after irradiation. Tissue slices were evaluated histopathologically. Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count. Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups, blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour. The retinal detachment rate was 100% at 3h and developed into bullous retinal detachment within 24h. Retinal hemorrhages were not observed until 24h. Clearance of the occluded veins at 7d was observed by fluorescein angiography. Disease manifestation in the central RVO eyes was more severe than in the branch RVO group. A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d, whereas moderate changes occurred in the branch RVO group.CONCLUSION: Rat RVO created by photochemically-induced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO. However, considering the 100% rate of retinal detachment, this animal model is more suitable for studying RVO with chronic retinal detachment.

  2. Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

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    Yuta Inokuchi

    2006-01-01

    Full Text Available Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retina in vitro and/or in vivo. In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2 exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation, as also did trolox (water-soluble vitamin E. In mice in vivo, propolis (100 mg kg−1; intraperitoneally administered four times reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer induced by intravitreal in vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage both in vitro and in vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

  3. Inner retinal change in a novel rd1-FTL mouse model of retinal degeneration

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    Ursula eGreferath

    2015-07-01

    Full Text Available While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1-Fos-Tau-LacZ (rd1-FTL mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei. The rd1-FTL model carries a mutation in the phosphodiesterase gene, Pde6b, and an axonally targeted transgenic beta galactosidase reporter system under the control of the c-fos promoter. Retinae of transgenic rd1-FTL mice and control FTL animals aged 2 to 12 months were processed for indirect fluorescence immunocytochemistry. At 2 months of age, a time when the majority of photoreceptor nuclei are lost, there was negligible c-fos reporter (FTL expression, however, from 4 months, reporter expression was observed to increase within subpopulations of amacrine and ganglion cells within the central retina. These areas of inner retinal FTL expression coincided with regions that contained aberrant Müller cells. Specifically, these cells exhibited reduced glutamine synthetase and Kir4.1 immunolabelling, whilst showing evidence of proliferative gliosis (increased cyclinD1 and GFAP expression. These changes were limited to distinct regions where cone photoreceptor terminals were absent. Overall, these results highlight that distinct areas of the rd1-FTL central retina undergo significant glial alterations after cone photoreceptor loss. These areas coincide with up-regulation of the c-fos reporter in the inner retina, which may represent a change in neuronal function/plasticity. The rd1-FTL mouse is a useful model system to probe changes that occur in the inner retina at later stages of retinal degeneration.

  4. Maternal enrichment during pregnancy accelerates retinal development of the fetus.

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    Alessandro Sale

    Full Text Available The influence of maternal environment on fetal development is largely unexplored, the available evidence concerns only the deleterious effects elicited by prenatal stress. Here we investigated the influence of prenatal enrichment on the early development of the visual system in the fetus. We studied the anatomical development of the rat retina, by analyzing the migration of neural progenitors and the process of retinal ganglion cell death, which exerts a key role in sculpturing the developing retinal system at perinatal ages. The number of apoptotic cells in the retinal ganglion cell layer was analyzed using two distinct methods: the presence of pyknotic nuclei stained for cresyl violet and the appearance of DNA fragmentation (Tunel method. We report that environmental enrichment of the mother during pregnancy affects the structural maturation of the retina, accelerating the migration of neural progenitors and the dynamics of natural cell death. These effects seem to be under the control of insulin-like growth factor-I: its levels, higher in enriched pregnant rats and in their milk, are increased also in their offspring, its neutralization abolishes the action of maternal enrichment on retinal development and chronic insulin-like growth factor-I injection to standard-reared females mimics the effects of enrichment in the fetuses. Thus, the development of the visual system is sensitive to environmental stimulation during prenatal life. These findings could have a bearing in orienting clinical research in the field of prenatal therapy.

  5. Statistical wiring of thalamic receptive fields optimizes spatial sampling of the retinal image

    Science.gov (United States)

    Wang, Xin; Sommer, Friedrich T.; Hirsch, Judith A.

    2014-01-01

    Summary It is widely assumed that mosaics of retinal ganglion cells establish the optimal representation of visual space. However, relay cells in the visual thalamus often receive convergent input from several retinal afferents and, in cat, outnumber ganglion cells. To explore how the thalamus transforms the retinal image, we built a model of the retinothalamic circuit using experimental data and simple wiring rules. The model shows how the thalamus might form a resampled map of visual space with the potential to facilitate detection of stimulus position in the presence of sensor noise. Bayesian decoding conducted with the model provides support for this scenario. Despite its benefits, however, resampling introduces image blur, thus impairing edge perception. Whole-cell recordings obtained in vivo suggest that this problem is mitigated by arrangements of excitation and inhibition within the receptive field that effectively boost contrast borders, much like strategies used in digital image processing. PMID:24559681

  6. Retinal dendritic cell recruitment, but not function, was inhibited in MyD88 and TRIF deficient mice

    OpenAIRE

    Heuss, Neal D; Pierson, Mark J; Montaniel, Kim Ramil C; McPherson, Scott W; Lehmann, Ute; Hussong, Stacy A; Ferrington, Deborah A; Low, Walter C; Gregerson, Dale S

    2014-01-01

    Background Immune system cells are known to affect loss of neurons due to injury or disease. Recruitment of immune cells following retinal/CNS injury has been shown to affect the health and survival of neurons in several models. We detected close, physical contact between dendritic cells and retinal ganglion cells following an optic nerve crush, and sought to understand the underlying mechanisms. Methods CD11c-DTR/GFP mice producing a chimeric protein of diphtheria toxin receptor (DTR) and GF...

  7. From retinal waves to activity-dependent retinogeniculate map development.

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    Jeffrey Markowitz

    Full Text Available A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+-activated K(+ channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

  8. Missed retinal breaks in rhegmatogenous retinal detachment

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    Brijesh Takkar

    2016-12-01

    Full Text Available AIM: To evaluate the causes and associations of missed retinal breaks (MRBs and posterior vitreous detachment (PVD in patients with rhegmatogenous retinal detachment (RRD. METHODS: Case sheets of patients undergoing vitreo retinal surgery for RRD at a tertiary eye care centre were evaluated retrospectively. Out of the 378 records screened, 253 were included for analysis of MRBs and 191 patients were included for analysis of PVD, depending on the inclusion criteria. Features of RRD and retinal breaks noted on examination were compared to the status of MRBs and PVD detected during surgery for possible associations. RESULTS: Overall, 27% patients had MRBs. Retinal holes were commonly missed in patients with lattice degeneration while missed retinal tears were associated with presence of complete PVD. Patients operated for cataract surgery were significantly associated with MRBs (P=0.033 with the odds of missing a retinal break being 1.91 as compared to patients with natural lens. Advanced proliferative vitreo retinopathy (PVR and retinal bullae were the most common reasons for missing a retinal break during examination. PVD was present in 52% of the cases and was wrongly assessed in 16%. Retinal bullae, pseudophakia/aphakia, myopia, and horse shoe retinal tears were strongly associated with presence of PVD. Traumatic RRDs were rarely associated with PVD. CONCLUSION: Pseudophakic patients, and patients with retinal bullae or advanced PVR should be carefully screened for MRBs. Though Weiss ring is a good indicator of PVD, it may still be over diagnosed in some cases. PVD is associated with retinal bullae and pseudophakia, and inversely with traumatic RRD.

  9. Retinal layer location of increased retinal thickness in eyes with subclinical and clinical macular edema in diabetes type 2

    DEFF Research Database (Denmark)

    Bandello, Francesco; Tejerina, Amparo Navea; Vujosevic, Stela

    2015-01-01

    PURPOSE: To identify the retinal layer predominantly affected in eyes with subclinical and clinical macular edema in diabetes type 2. METHODS: A cohort of 194 type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20/35) were examined with Cirrus spectral......-domain optical coherence tomography (OCT) at the baseline visit (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers of the eyes with subclinical and clinical macular edema was compared with a sample of 31 eyes from diabetic patients with normal OCT and an age......). Increases were also found in the neighboring layers. Thinning of the retina was registered in the retinal nerve fiber, ganglion cells and inner plexiform layers in the diabetic eyes without macular edema. CONCLUSIONS: The increase in RT occurring in diabetic eyes with macular edema is predominantly located...

  10. Ganglion cell adaptability: does the coupling of horizontal cells play a role?

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    Karin Dedek

    Full Text Available BACKGROUND: The visual system can adjust itself to different visual environments. One of the most well known examples of this is the shift in spatial tuning that occurs in retinal ganglion cells with the change from night to day vision. This shift is thought to be produced by a change in the ganglion cell receptive field surround, mediated by a decrease in the coupling of horizontal cells. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we used a transgenic mouse line, a connexin57-deficient line, in which horizontal cell coupling was abolished. Measurements, both at the ganglion cell level and the level of behavioral performance, showed no differences between wild-type retinas and retinas with decoupled horizontal cells from connexin57-deficient mice. CONCLUSION/SIGNIFICANCE: This analysis showed that the coupling and uncoupling of horizontal cells does not play a dominant role in spatial tuning and its adjustability to night and day light conditions. Instead, our data suggest that another mechanism, likely arising in the inner retina, must be responsible.

  11. Transsacrococcygeal approach to ganglion impar block for treatment of chronic coccygodynia after spinal arachnoid cyst removal

    Science.gov (United States)

    Cha, Young Deog; Yang, Chun Woo; Han, Jung Uk; Song, Jang Ho; Na, WonJu; Oh, Sora; Kim, Byung-Gun

    2016-01-01

    Abstract Background: Coccygodynia is a pain in the region of the coccyx that radiates to the sacral, perineal area. The cause of the pain is often unknown. Coccygodynia is diagnosed through the patient's past history, a physical examination, and dynamic radiographic study, but the injection of local anesthetics or a diagnostic nerve blockade are needed to distinguish between somatic, neuropathic, and combined pain. Ganglion impar is a single retroperitoneal structure made of both paravertebral sympathetic ganglions. Although there are no standard guidelines for the treatment of coccygodynia, ganglion impar blockade is one of the effective options for treatment. Methods: Here, we report a 42-year-old female patient presenting with severe pain in the coccygeal area after spinal arachnoid cyst removal. Results: Treatment involved neurolysis with absolute alcohol on the ganglion impar through the transsacrococcygeal junction. Pain was relieved without any complications. Conclusion: Our case report offers the ganglion impar blockade using the transsacrococcygeal approach with absolute alcohol can improve intractable coccydynia. PMID:27684866

  12. Intraocular retinal prosthesis.

    Science.gov (United States)

    Humayun, M S

    2001-01-01

    An electronic implant that can bypass the damaged photoreceptors and electrically stimulate the remaining retinal neurons to restore useful vision has been proposed. A number of key questions remain to make this approach feasible. The goal of this thesis is to address the following 2 specific null hypotheses: (1) Stimulus parameters make no difference in the electrically elicited retinal responses. (2) Just as we have millions of photoreceptors, so it will take a device that can generate millions of pixels/light points to create useful vision. For electrophysiologic experiments, 2 different setups were used. In the first setup, charge-balanced pulses were delivered to the retinal surface via electrodes inserted through an open sky approach in normal or blind retinal degenerate (rd) mice. In the second setup, the rabbit retina was removed under red light conditions from an enucleated eye and then maintained in a chamber while being superfused with oxygenated, heated Ames media. In both setups, stimulating electrodes and recording electrodes were positioned on the retinal surface to evaluate the effect of varying stimulation parameters on the orthodromic retinal responses (i.e., recording electrode placed between stimulating electrodes and optic nerve head). For psychophysical experiments, visual images were divided into pixels of light that could be projected in a pattern on the retina in up to 8 sighted volunteers. Subjects were asked to perform various tasks ranging from reading and face recognition to various activities of daily living. Electrophysiologic experiments: In a normal mouse, a single cycle of a 1-kHz sine wave was significantly more efficient than a 1-kHz square wave (P < .05), but no such difference was noted in either of the 8- or 16-week-old rd mouse groups (8-week-old, P = .426; 16-week-old, P = .078). Charge threshold was significantly higher in 16-week-old rd mouse versus both 8-week-old rd and normal mouse for every stimulus duration (P < .05

  13. Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

    Science.gov (United States)

    Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

    2015-01-01

    Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

  14. Astrocytes and Müller cells changes during retinal degeneration in a transgenic rat model of retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Laura eFernández-Sánchez

    2015-12-01

    Full Text Available Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer of P23H versus SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.

  15. Ciliary neurotrophic factor: a survival and differentiation inducer in human retinal progenitors.

    Science.gov (United States)

    Dutt, Kamla; Cao, Yang; Ezeonu, Ifeoma

    2010-07-01

    Retinitis pigmentosa, age-related macular degeneration, and Parkinson's disease remain major problems in the field of medicine. Some of the strategies being explored for treatment include replacement of damaged tissue by transplantation of healthy tissues or progenitor cells and delivery of neurotrophins to rescue degenerating tissue. One of the neurotrophins with promise is the ciliary neurotrophic factor (CNTF). In this study, we report the role played by CNTF in retinal cell differentiation and survival in retinal progenitors. We found that CNTF is a survival factor for multipotential human retinal cells and increased cell survival by 50%, over a 7-d period, under serum-free conditions, as determined by apoptotic assays (immunohistochemistry and flow cytometry). This effect is dose dependent with a maximum survival at a CNTF concentration of 20 ng/ml. We also report that CNTF might be a cell commitment factor, directing the differentiation mainly toward large multipolar cells with ganglionic and amacrine phenotype. These cells express tyrosine hydroxylase (amacrine cells) as well as, thy 1.1 and neuron-specific enolase (ganglionic cells). Additionally, there was also an increase in protein kinase C alpha, a protein expressed in rod and cone bipolars as well as cone photoreceptors and calbindin, a protein expressed in cone photoreceptors and horizontal cells. In our studies, CNTF doubled the number of cells with ganglionic phenotypes, and basic fibroblast growth factor doubled the number of cells with photoreceptor phenotype. Additionally, CNTF induced a subset of progenitors to undergo multiple rounds of cell division before acquiring the large multipolar ganglionic phenotype. Our conclusion is that CNTF could be an agent that has therapeutic potential and possibly induces differentiation of large multipolar ganglionic phenotype in a subset of progenitors.

  16. Effects of LAR and PTP-BL phosphatase deficiency on adult mouse retinal cells activated by lens injury.

    NARCIS (Netherlands)

    Lorber, B.; Hendriks, W.J.A.J.; Zee, C.E.E.M. van der; Berry, M.; Logan, A.

    2005-01-01

    Using intact and lens-lesioned wildtype, leucocyte common antigen-related phosphatase deficient (LARDeltaP) and protein tyrosine phosphatase (PTP)-BAS-like phosphatase deficient (PTP-BLDeltaP) mice, we have evaluated the role of LAR and PTP-BL in retinal ganglion cell survival and neuritogenesis,

  17. Finite element modeling of retinal prosthesis mechanics

    Science.gov (United States)

    Basinger, B. C.; Rowley, A. P.; Chen, K.; Humayun, M. S.; Weiland, J. D.

    2009-10-01

    Epiretinal prostheses used to treat degenerative retina diseases apply stimulus via an electrode array fixed to the ganglion cell side of the retina. Mechanical pressure applied by these arrays to the retina, both during initial insertion and throughout chronic use, could cause sufficient retinal damage to reduce the device's effectiveness. In order to understand and minimize potential mechanical damage, we have used finite element analysis to model mechanical interactions between an electrode array and the retina in both acute and chronic loading configurations. Modeling indicates that an acute tacking force distributes stress primarily underneath the tack site and heel edge of the array, while more moderate chronic stresses are distributed more evenly underneath the array. Retinal damage in a canine model chronically implanted with a similar array occurred in correlating locations, and model predictions correlate well with benchtop eyewall compression tests. This model provides retinal prosthesis researchers with a tool to optimize the mechanical electrode array design, but the techniques used here represent a unique effort to combine a modifiable device and soft biological tissues in the same model and those techniques could be extended to other devices that come into mechanical contact with soft neural tissues.

  18. Aldose reductase mediates retinal microglia activation

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kun-Che; Shieh, Biehuoy; Petrash, J. Mark, E-mail: mark.petrash@ucdenver.edu

    2016-04-29

    Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1{sup GFP} mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migration in vivo. When tested on an AR{sup WT} background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-α and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy. - Highlights: • AR inhibition prevents retinal microglial activation. • Endotoxin-induced ocular cytokine production is reduced in AR null mice. • Overexpression of AR spontaneously induces retinal microglial activation.

  19. Retinal Imaging with Smartphone

    African Journals Online (AJOL)

    2016-08-23

    10) for retinal imaging in a resource-limited economy. Methods: A ... information sharing. Retinal Imaging with Smartphone. Address for correspondence: Dr. Dupe S. Ademola-. Popoola, Department of Ophthalmology, University ...

  20. Retinal layer measurements after successful macula-off retinal detachment repair using optical coherence tomography.

    Science.gov (United States)

    Menke, Marcel N; Kowal, Jens H; Dufour, Pascal; Wolf-Schnurrbusch, Ute E; Ceklic, Lala; Framme, Carsten; Wolf, Sebastian

    2014-09-04

    Optical coherence tomography (OCT) was used to analyze the thickness of various retinal layers of patients following successful macula-off retinal detachment (RD) repair. Optical coherence tomography scans of patients after successful macula-off RD repair were reanalyzed with a subsegmentation algorithm to measure various retinal layers. Regression analysis was performed to correlate time after surgery with changes in layer thickness. In addition, patients were divided in two groups. Group 1 had a follow-up period after surgery of up to 7 weeks (range, 21-49 days). In group 2, the follow-up period was >8 weeks (range, 60-438 days). Findings were compared to a group of age-matched healthy controls. Correlation analysis showed a significant positive correlation between inner nuclear-outer plexiform layer (INL-OPL) thickness and time after surgery (P=0.0212; r2=0.1551). Similar results were found for the ellipsoid zone-retinal pigment epithelium complex (EZ-RPE) thickness (P=0.005; r2=0.2215). Ganglion cell-inner plexiform layer thickness (GCL-IPL) was negatively correlated with time after surgery (P=0.0064; r2=0.2101). For group comparison, the retinal nerve fiber layer in both groups was thicker compared to controls. The GCL-IPL showed significant thinning in group 2. The outer nuclear layer was significantly thinner in groups 1 and 2 compared to controls. The EZ-RPE complex was significantly thinner in groups 1 and 2 compared to controls. In addition, values in group 1 were significantly thinner than in group 2. Optical coherence tomography retinal layer thickness measurements after successful macular-off RD repair revealed time-dependent thickness changes. Inner nuclear-outer plexiform layer thickness and EZ-RPE thickness was positively correlated with time after surgery. Ganglion cell-inner plexiform layer thickness was negatively correlated with time after surgery. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  1. Piriformis ganglion: An uncommon cause of sciatica.

    Science.gov (United States)

    Park, J H; Jeong, H J; Shin, H K; Park, S J; Lee, J H; Kim, E

    2016-04-01

    Sciatica can occur due to a spinal lesion, intrapelvic tumor, diabetic neuropathy, and rarely piriformis syndrome. The causes of piriformis syndrome vary by a space-occupying lesion. A ganglionic cyst can occur in various lesions in the body but seldom around the hip joint. In addition, sciatica due to a ganglionic cyst around the hip joint has been reported in one patient in Korea who underwent surgical treatment. We experienced two cases of sciatica from a piriformis ganglionic cyst and we report the clinical characterics and progress after non-operative treatment by ultrasonography-guided aspiration. The two cases were diagnosed by magnetic resonance imaging and were treated by ultrasonography-guided aspiration. We followed the patients for more than 6months. The symptoms of piriformis syndrome from the ganglion improved following aspiration and this conservative treatment is a treatment method that can be used without extensive incision or cyst excision. Level IV historical case. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Ganglion cell loss in relation to visual disability in multiple sclerosis.

    Science.gov (United States)

    Walter, Scott D; Ishikawa, Hiroshi; Galetta, Kristin M; Sakai, Reiko E; Feller, Daniel J; Henderson, Sam B; Wilson, James A; Maguire, Maureen G; Galetta, Steven L; Frohman, Elliot; Calabresi, Peter A; Schuman, Joel S; Balcer, Laura J

    2012-06-01

    We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS). Cross-sectional study. A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment. The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined. The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score. Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (Pvisual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS. Proprietary or commercial disclosure may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  3. Retinal prosthetics, optogenetics, and chemical photoswitches.

    Science.gov (United States)

    Marc, Robert; Pfeiffer, Rebecca; Jones, Bryan

    2014-10-15

    Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream

  4. Decreased retinal sensitivity in depressive disorder

    DEFF Research Database (Denmark)

    Berman, G.; Muttuvelu, D.; Berman, D.

    2018-01-01

    . The pupil light reflex was measured at inclusion and in the following summer using a binocular pupillometer. A protocol of low (1 lux) and high (400 lux) intensity red and blue lights was used to assess rod, cone and melanopsin-containing intrinsic photosensitive retinal ganglion cell input to the pupil...... reflex. RESULTS: The mean group pupil responses associated with a melanopsin-mediated sustained pupil response at 400 lux blue light were significantly reduced in the depressed subjects (N = 39) as compared to the healthy controls (N = 24) (P = 0.023). Across all groups, a reduction in number of daylight...... hours was significantly associated with a reduction in sustained pupil response (P = 0.007). All groups showed an equal effect of daylight hours on the melanopsin-mediated sustained pupil response. CONCLUSION: The melanopsin-mediated sustained pupil contraction to offset of high-intensity blue light...

  5. Intersecting circuits generate precisely patterned retinal waves.

    Science.gov (United States)

    Akrouh, Alejandro; Kerschensteiner, Daniel

    2013-07-24

    The developing retina generates spontaneous glutamatergic (stage III) waves of activity that sequentially recruit neighboring ganglion cells with opposite light responses (ON and OFF RGCs). This activity pattern is thought to help establish parallel ON and OFF pathways in downstream visual areas. The circuits that produce stage III waves and desynchronize ON and OFF RGC firing remain obscure. Using dual patch-clamp recordings, we find that ON and OFF RGCs receive sequential excitatory input from ON and OFF cone bipolar cells (CBCs), respectively. This input sequence is generated by crossover circuits, in which ON CBCs control glutamate release from OFF CBCs via diffusely stratified inhibitory amacrine cells. In addition, neighboring ON CBCs communicate directly and indirectly through lateral glutamatergic transmission and gap junctions, both of which are required for wave initiation and propagation. Thus, intersecting lateral excitatory and vertical inhibitory circuits give rise to precisely patterned stage III retinal waves. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Histogenesis of retinal dysplasia in trisomy 13

    Directory of Open Access Journals (Sweden)

    Gonzalez-Fernandez Federico

    2007-12-01

    Full Text Available Abstract Background Although often associated with holoprosencephaly, little detail of the histopathology of cyclopia is available. Here, we describe the ocular findings in a case of trisomy 13 to better understand the histogenesis of the rosettes, or tubules, characteristic of the retinal dysplasia associated with this condition. Methods A full pediatric autopsy was performed of a near term infant who died shortly after birth from multiple congenital anomalies including fused facial-midline structures. A detailed histopathological study of the ocular structures was performed. The expression of interphotoreceptor retinoid-binding protein (IRBP, cellular retinal-binding protein (CRALBP, rod opsin, and Sonic Hedgehog (Shh were studied by immunohistochemistry. Results Holoprosencephaly, and a spectrum of anatomical findings characteristic of Patau's syndrome, were found. Cytogenetic studies demonstrated trisomy 13 [47, XY, +13]. The eyes were fused but contained two developed separate lenses. In contrast, the cornea, and angle structures were hypoplastic, and the anterior chamber had failed to form. The retina showed areas of normally laminated neural retina, whereas in other areas it was replaced by numerous neuronal rosettes. Histological and immunohistochemical studies revealed that the rosettes were composed of differentiated retinal neurons and Müller cell glia. In normally laminated retina, Shh expression was restricted to retinal-ganglion cells, and to a population of neurons in the inner zone of the outer nuclear layer. In contrast, Shh could not be detected in the dysplastic rosettes. Conclusion The histopathology of cyclopia appears to be more complex than what may have been previously appreciated. In fact, the terms "cyclopia" and "synophthalmia" are misnomers as the underlying mechanism is a failure of the eyes to form separately during development. The rosettes found in the dysplastic retina are fundamentally different than those of

  7. Histogenesis of retinal dysplasia in trisomy 13

    Science.gov (United States)

    Chan, Ada; Lakshminrusimha, Satyan; Heffner, Reid; Gonzalez-Fernandez, Federico

    2007-01-01

    Background Although often associated with holoprosencephaly, little detail of the histopathology of cyclopia is available. Here, we describe the ocular findings in a case of trisomy 13 to better understand the histogenesis of the rosettes, or tubules, characteristic of the retinal dysplasia associated with this condition. Methods A full pediatric autopsy was performed of a near term infant who died shortly after birth from multiple congenital anomalies including fused facial-midline structures. A detailed histopathological study of the ocular structures was performed. The expression of interphotoreceptor retinoid-binding protein (IRBP), cellular retinal-binding protein (CRALBP), rod opsin, and Sonic Hedgehog (Shh) were studied by immunohistochemistry. Results Holoprosencephaly, and a spectrum of anatomical findings characteristic of Patau's syndrome, were found. Cytogenetic studies demonstrated trisomy 13 [47, XY, +13]. The eyes were fused but contained two developed separate lenses. In contrast, the cornea, and angle structures were hypoplastic, and the anterior chamber had failed to form. The retina showed areas of normally laminated neural retina, whereas in other areas it was replaced by numerous neuronal rosettes. Histological and immunohistochemical studies revealed that the rosettes were composed of differentiated retinal neurons and Müller cell glia. In normally laminated retina, Shh expression was restricted to retinal-ganglion cells, and to a population of neurons in the inner zone of the outer nuclear layer. In contrast, Shh could not be detected in the dysplastic rosettes. Conclusion The histopathology of cyclopia appears to be more complex than what may have been previously appreciated. In fact, the terms "cyclopia" and "synophthalmia" are misnomers as the underlying mechanism is a failure of the eyes to form separately during development. The rosettes found in the dysplastic retina are fundamentally different than those of retinoblastoma, being

  8. Branched chain amino acids attenuate major pathologies in mouse models of retinal degeneration and glaucoma.

    Science.gov (United States)

    Hasegawa, Tomoko; Ikeda, Hanako Ohashi; Iwai, Sachiko; Muraoka, Yuki; Tsuruyama, Tatsuaki; Okamoto-Furuta, Keiko; Kohda, Haruyasu; Kakizuka, Akira; Yoshimura, Nagahisa

    2018-02-01

    Retinal neuronal cell death underlies many incurable eye diseases such as retinitis pigmentosa (RP) and glaucoma, and causes adult blindness. We have shown that maintenance of ATP levels via inhibiting ATP consumption is a promising strategy for preventing neuronal cell death. Here, we show that branched chain amino acids (BCAAs) are able to increase ATP production by enhancing glycolysis. In cell culture, supplementation of the culture media with BCAAs, but not glucose alone, enhanced cellular ATP levels, which was canceled by a glycolysis inhibitor. Administration of BCAAs to RP mouse models, rd10 and rd12 , significantly attenuated photoreceptor cell death morphologically and functionally, even when administration was started at later stages. Administration of BCAAs in a glaucoma mouse model also showed significant attenuation of retinal ganglion cell death. These results suggest that administration of BCAAs could contribute to a comprehensive therapeutic strategy for retinal neurodegenerative diseases such as RP and glaucoma.

  9. Retinal cell imaging in myopic chickens using adaptive optics multiphoton microscopy.

    Science.gov (United States)

    Bueno, Juan M; Palacios, Raquel; Giakoumaki, Anastasia; Gualda, Emilio J; Schaeffel, Frank; Artal, Pablo

    2014-03-01

    Abnormal eye growth induced by visual deprivation can modify the structure and density of the retinal cells. We have used an adaptive optics multiphoton microscope to image photoreceptors (PRs) and ganglion cells (GCs) at different retinal locations in unstained retinas of chicken eyes with about 10D of myopia and their normal-sighted fellow eyes. In all samples, the local averaged inter-PR distance increased with eccentricity. No significant differences in PR density were found between control and myopic eyes. GC density declined in myopic eyes compared to control eyes and the inter-cell distance increased. In normal eyes, the size of the GC cell bodies increased approximately two-fold between the area centralis and the peripheral retina. In myopic eyes, this trend was preserved but the GC bodies were larger at each retinal location, compared to control eyes. Obviously, GC morphology is changing when the retinal area is enlarged in myopic eyes.

  10. FluoroGold-Labeled Organotypic Retinal Explant Culture for Neurotoxicity Screening Studies

    Directory of Open Access Journals (Sweden)

    Adrian Smedowski

    2018-01-01

    Full Text Available Preclinical toxicity screening of the new retinal compounds is an absolute requirement in the pathway of further drug development. Since retinal neuron cultivation and in vivo studies are relatively expensive and time consuming, we aimed to create a fast and reproducible ex vivo system for retinal toxicity screening. For this purpose, we used rat retinal explant culture that was retrogradely labeled with the FluoroGold before the isolation. Explants were exposed to a toxic concentration of gentamicin and ciliary neurotrophic factor (CNTF, a known neuroprotective agent. The measured outcomes showed the cell density in retinal ganglion cell layer (GCL and the activity of lactate dehydrogenase (LDH in the culture medium. Gentamicin-induced oxidative stress resulted in retinal cell damage and rapid LDH release to the culture medium (p0.05. As well as this, the LDH activity was directly correlated with the cell count in GCL (R=−0.84, p<0.00001, making a sensitive marker of retinal neuron damage. The FLOREC protocol could be considered as a fast, reproducible, and sensitive method to detect neurotoxicity in the screening studies of the retinal drugs.

  11. Whole exome sequencing identified a novel single base pair insertion mutation in the EYS gene in a six generation family with retinitis pigmentosa.

    Science.gov (United States)

    Hashmi, Jamil Amjad; Albarry, Maan Abdullah; Almatrafi, Ahmed M; Albalawi, Alia M; Mahmood, Amer; Basit, Sulman

    2018-01-01

    Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) and is characterized by photoreceptor degeneration. RP is clinically and genetically heterogeneous disorder. More than 70 genes are known and, thus, identification of causative genes and mutations in known genes is challenging. This study was designed to identify the underlying genetic defect in a large extended Saudi family with multiple RP affected members. Fundus photography, Optical Coherence Tomography (OCT) and visual field perimetry were performed for affected individuals. Whole exome sequencing was used to detect the underlying genetic defect in a large family with 12 affected individuals showing autosomal recessive isolated RP. WES data analysis identified a novel insertion mutation in the EYS (eyes shut homolog) gene (c.910_911insT; p.Trp304LeufsTer8). Sanger sequencing validates the variant discovered through exome in all 12 affected individuals and showed that this mutation is segregating with RP phenotype in an autosomal recessive manner in 51 individuals of the family tested here. Our study expands the mutation spectrum of EYS gene in RP patients and extends the body of evidence that supports the importance of EYS gene in eye development. © 2017 Japanese Teratology Society.

  12. Learning LM Specificity for Ganglion Cells

    Science.gov (United States)

    Ahumada, Albert J.

    2015-01-01

    Unsupervised learning models have been proposed based on experience (Ahumada and Mulligan, 1990;Wachtler, Doi, Lee and Sejnowski, 2007) that allow the cortex to develop units with LM specific color opponent receptive fields like the blob cells reported by Hubel and Wiesel on the basis of visual experience. These models used ganglion cells with LM indiscriminate wiring as inputs to the learning mechanism, which was presumed to occur at the cortical level.

  13. Sustained intraocular VEGF neutralization results in retinal neurodegeneration in the Ins2(Akita) diabetic mouse.

    Science.gov (United States)

    Hombrebueno, Jose R; Ali, Imran H A; Xu, Heping; Chen, Mei

    2015-12-16

    Current therapies that target vascular endothelial growth factor (VEGF) have become a mainstream therapy for the management of diabetic macular oedema. The treatment involves monthly repeated intravitreal injections of VEGF inhibitors. VEGF is an important growth factor for many retinal cells, including different types of neurons. In this study, we investigated the adverse effect of multiple intravitreal anti-VEGF injections (200 ng/μl/eye anti-mouse VEGF164, once every 2 weeks totalling 5-6 injections) to retinal neurons in Ins2(Akita) diabetic mice. Funduscopic examination revealed the development of cotton wool spot-like lesions in anti-VEGF treated Ins2(Akita) mice after 5 injections. Histological investigation showed focal swellings of retinal nerve fibres with neurofilament disruption. Furthermore, anti-VEGF-treated Ins2(Akita) mice exhibited impaired electroretinographic responses, characterized by reduced scotopic a- and b-wave and oscillatory potentials. Immunofluorescent staining revealed impairment of photoreceptors, disruptions of synaptic structures and loss of amacrine and retinal ganglion cells in anti-VEGF treated Ins2(Akita) mice. Anti-VEGF-treated WT mice also presented mild amacrine and ganglion cell death, but no overt abnormalities in photoreceptors and synaptic structures. At the vascular level, exacerbated albumin leakage was observed in anti-VEGF injected diabetic mice. Our results suggest that sustained intraocular VEGF neutralization induces retinal neurodegeneration and vascular damage in the diabetic eye.

  14. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    Science.gov (United States)

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases.

  15. Comparison of eye morphology and retinal topography in two species of new world vultures (Aves: Cathartidae)

    DEFF Research Database (Denmark)

    Lisney, Thomas J.; Stecyk, Karyn; Kolominsky, Jeffrey

    2013-01-01

    aura), with a highly developed olfactory sense, and black vultures (Coragyps atratus), with a less developed sense of olfaction. We found that eye size relative to body mass was the same in both species, but that black vultures have larger corneas relative to eye size than turkey vultures. However......, the overall retinal topography, the total number of cells in the retinal ganglion cell layer, peak and average cell densities, cell soma area frequency distributions, and the theoretical peak anatomical spatial resolving power were the same in both species. This suggests that the visual systems of these two...

  16. ["Point by point" approach to structure-function correlation of glaucoma on the ganglion cell complex in the posterior pole].

    Science.gov (United States)

    Zeitoun, M

    2017-01-01

    To try to establish a "point by point" relationship between the local thickness of the retinal ganglion cell complex and its sensitivity. In total, 104 glaucomatous eyes of 89 patients with a confirmed 24-2 visual field, were measured by superimposing the visual field, using imaging software, with the Wide 40° by 30° measurements of retinal ganglion cell complex obtained from the Topcon © 3D 2000 OCT, after upward adjustment, inversion and scaling. Visual fields were classified into two groups according to the extent of the disease: 58 mild to moderate (MD up to -12dB), and 46 severe (MD beyond -12dB). The 6mm by 6mm central region, equipped with a normative database, was studied, corresponding to 16 points in the visual field. These points were individually matched one by one to the local ganglion cell complex, which was classified into 2 groups depending on whether it was greater or less than 70 microns. The normative database confirmed the pathological nature of the thin areas, with a significance of 95 to 99%. Displacement of central retinal ganglion cells was compensated for. Of 1664 points (16 central points for 104 eyes), 283 points were found to be "borderline" and excluded. Of the 1381 analyzed points, 727 points were classified as "over 70 microns" and 654 points "under 70 microns". (1) For all stages combined, 85.8% of the 727 points which were greater than 70 microns had a deviation between -3 and +3dB: areas above 70 microns had no observable loss of light sensitivity. (2) In total, 92.5% of the 428 points having a gap ranging from -6 to -35dB were located on ganglion cell complex areas below 70 microns: functional visual loss was identified in thin areas, which were less than 70 microns. (3) Areas which were less than 70 microns, that is 654 points, had quite variable sensitivity and can be divided into three groups: the first with preserved sensitivity, another with obliterated sensitivity, and an intermediate group connecting

  17. Treatment of temporomandibular joint ganglion cyst.

    Science.gov (United States)

    Wu, Chao-I; Liu, Ka-Wai; Hsu, Yung-Chang; Chiang, I-Ping; Chang, Sophia Chia-Ning

    2011-09-01

    Ganglion cysts of the temporomandibular joint are very rare and always misdiagnosed as synovial cyst, parotid gland tumor, or other cystic lesions. They present with pain, swelling, or dysfunction. Image studies could facilitate to identify the tumor mass from the adjacent soft tissue, but a definitive diagnosis could be made from the pathologic report.A 59-year-old woman presented to the clinics with a chief complaint of a painless swelling mass in the right preauricular region of 3-month duration. Computed tomography was performed, which showed a small radiolucent lesion adjacent to the right condyle. Local excision was performed, and the specimen was sent for histologic examination.Microscopic examination showed a cystic space walled by dense fibrous connective tissue without epithelial or endothelial lining. Immunohistochemical staining of these lining cells showed positivity for vimentin and negativity for cytokeratin. These findings were consistent with the diagnosis of ganglion cyst.Ganglion cysts present as unilobulate or multilobulate cysts that arise from the collagenous tissue and is filled with highly viscous fluid. It does not communicate with the joint cavity. In contrast, synovial cyst is a true cyst lined by cuboidal or flattened cells from the synoviocytes and is filled with gelatinous fluid. It may or may not communicate with the joint cavity. Excision is the treatment of choice of symptomatic cystic lesions. Incomplete excision of these lesions may cause further recurrence or infection. Thus, injection of hydrocortisone or aspiration may be considered as an alternative management.

  18. Lycium barbarum polysaccharides reduce neuronal damage, blood-retinal barrier disruption and oxidative stress in retinal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Suk-Yee Li

    Full Text Available Neuronal cell death, glial cell activation, retinal swelling and oxidative injury are complications in retinal ischemia/reperfusion (I/R injuries. Lycium barbarum polysaccharides (LBP, extracts from the wolfberries, are good for "eye health" according to Chinese medicine. The aim of our present study is to explore the use of LBP in retinal I/R injury. Retinal I/R injury was induced by surgical occlusion of the internal carotid artery. Prior to induction of ischemia, mice were treated orally with either vehicle (PBS or LBP (1 mg/kg once a day for 1 week. Paraffin-embedded retinal sections were prepared. Viable cells were counted; apoptosis was assessed using TUNEL assay. Expression levels of glial fibrillary acidic protein (GFAP, aquaporin-4 (AQP4, poly(ADP-ribose (PAR and nitrotyrosine (NT were investigated by immunohistochemistry. The integrity of blood-retinal barrier (BRB was examined by IgG extravasations. Apoptosis and decreased viable cell count were found in the ganglion cell layer (GCL and the inner nuclear layer (INL of the vehicle-treated I/R retina. Additionally, increased retinal thickness, GFAP activation, AQP4 up-regulation, IgG extravasations and PAR expression levels were observed in the vehicle-treated I/R retina. Many of these changes were diminished or abolished in the LBP-treated I/R retina. Pre-treatment with LBP for 1 week effectively protected the retina from neuronal death, apoptosis, glial cell activation, aquaporin water channel up-regulation, disruption of BRB and oxidative stress. The present study suggests that LBP may have a neuroprotective role to play in ocular diseases for which I/R is a feature.

  19. Chitosan oligosaccharides attenuates oxidative-stress related retinal degeneration in rats.

    Directory of Open Access Journals (Sweden)

    I-Mo Fang

    Full Text Available This study investigated the therapeutic potential and mechanisms of chitosan oligosaccharides (COS for oxidative stress-induced retinal diseases. Retinal oxidative damage was induced in Sprague-Dawley rats by intravitreal injection of paraquat (PQ. Low-dose (5 mg/kg or high-dose (10 mg/kg COS or PBS was intragastrically given for 14 days after PQ injection. Electroretinograms were performed to determine the functionality of the retinas. The surviving neurons in the retinal ganglion cell layer and retinal apoptosis were determined by counting Neu N-positive cells in whole-mounted retinas and TUNEL staining, respectively. The generation of reactive oxygen species (ROS was determined by lucigenin- and luminol-enhanced chemiluminescence. Retinal oxidative damages were assessed by staining with nitrotyrosine, acrolein, and 8-hydroxy-2'-deoxyguanosine (8-OHdG. Immunohistochemical studies were used to demonstrate the expression of nuclear factor-kappa B (NF-κB p65 in retinas. An in vitro study using RGC-5 cells was performed to verify the results. We demonstrated COS significantly enhanced the recovery of retinal function, preserved inner retinal thickness, and decreased retinal neurons loss in a dose-dependent manner. COS administration demonstrated anti-oxidative effects by reducing luminol- and lucigenin-dependent chemiluminenscense levels and activating superoxide dismutase and catalase, leading to decreased retinal apoptosis. COS markedly reduced retinal NF-κB p65. An in vitro study demonstrated COS increased IκB expression, attenuated the increase of p65 and thus decreased NF-κB/DNA binding activity in PQ-stimulated RGC-5 cells. In conclusion, COS attenuates oxidative stress-induced retinal damages, probably by decreasing free radicals, maintaining the activities of anti-oxidative enzymes, and inhibiting the activation of NF-κB.

  20. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    International Nuclear Information System (INIS)

    Kim, Yeoun-Hee; Chang, Yongmin; Jung, Jae-Chang

    2012-01-01

    Highlights: ► Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. ► Staurosporine mediates uPA activation during RGC differentiation in vitro. ► Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. ► Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that uPA plays a role in the staurosporine-mediated stimulation of RGC differentiation.

  1. Guidance of retinal axons in mammals.

    Science.gov (United States)

    Herrera, Eloísa; Erskine, Lynda; Morenilla-Palao, Cruz

    2017-11-26

    In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway. The proper formation of this pathway during development is essential for normal vision in the adult individual. Along this pathway there are several points where visual axons face 'choices' in their direction of growth. Understanding how these choices are made has advanced significantly our knowledge of axon guidance mechanisms. Thus, the development of the visual pathway has served as an extremely useful model to reveal general principles of axon pathfinding throughout the nervous system. However, due to its particularities, some cellular and molecular mechanisms are specific for the visual circuit. Here we review both general and specific mechanisms involved in the guidance of mammalian RGC axons when they are traveling from the retina to the brain to establish precise and stereotyped connections that will sustain vision. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Effect of axonal micro-tubules on the morphology of retinal nerve fibers studied by second-harmonic generation

    Science.gov (United States)

    Lim, Hyungsik; Danias, John

    2012-11-01

    Many studies suggest that the degradation of microtubules in the retinal ganglion cells may be an early event in the progression of glaucoma. Because reflectance and birefringence of the retinal nerve fibers arise primarily from microtubules, the optical properties have been intensively studied for early detection of the disease. We previously reported a novel nonlinear optical signal from axonal microtubules for visualizing the retinal nerve fibers, namely second-harmonic generation (SHG). We demonstrate the use of axonal SHG to investigate the effect of microtubules on the morphology of the retinal nerve fiber bundles. Time-lapse SHG imaging of ex vivo rat retinal flat mounts was performed during pharmacological treatment of nocodazole, and the intensity of axonal SHG and the changes in nerve fiber bundle morphology were monitored. We found that the microtubule disruption does not lead to immediate modification in the morphology of the nerve fibers. Our results indicate that microtubular SHG may provide a useful means for sensitive detection of axonal injuries. Since the intrinsic radiation depends on the regular architecture of the cytoskeleton element as maintained by active cellular regulations, the intensity of signal reflects the health of the retinal ganglion cell axons.

  3. NMDA Receptors Contribute to Retrograde Synaptic Transmission from Ganglion Cell Photoreceptors to Dopaminergic Amacrine Cells

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    Lei-Lei Liu

    2017-09-01

    Full Text Available Recently, a line of evidence has demonstrated that the vertebrate retina possesses a novel retrograde signaling pathway. In this pathway, phototransduction is initiated by the photopigment melanopsin, which is expressed in a small population of retinal ganglion cells. These ganglion cell photoreceptors then signal to dopaminergic amacrine cells (DACs through glutamatergic synapses, influencing visual light adaptation. We have previously demonstrated that in Mg2+-containing solution, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptors mediate this glutamatergic transmission. Here, we demonstrate that removing extracellular Mg2+ enhances melanopsin-based DAC light responses at membrane potentials more negative than −40 mV. Melanopsin-based responses in Mg2+-free solution were profoundly suppressed by the selective N-methyl-D-aspartate (NMDA receptor antagonist D-AP5. In addition, application of NMDA to the retina produced excitatory inward currents in DACs. These data strongly suggest that DACs express functional NMDA receptors. We further found that in the presence of Mg2+, D-AP5 reduced the peak amplitude of melanopsin-based DAC responses by ~70% when the cells were held at their resting membrane potential (−50 mV, indicating that NMDA receptors are likely to contribute to retrograde signal transmission to DACs under physiological conditions. Moreover, our data show that melanopsin-based NMDA-receptor-mediated responses in DACs are suppressed by antagonists specific to either the NR2A or NR2B receptor subtype. Immunohistochemical results show that NR2A and NR2B subunits are expressed on DAC somata and processes. These results suggest that DACs express functional NMDA receptors containing both NR2A and NR2B subunits. Collectively, our data reveal that, along with AMPA receptors, NR2A- and NR2B-containing NMDA receptors mediate retrograde signal transmission from ganglion cell photoreceptors to DACs.

  4. PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities.

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    Samba, R; Herrmann, T; Zeck, G

    2015-02-01

    The aim of this study was to compare two different microelectrode materials--the conductive polymer composite poly-3,4-ethylenedioxythiophene (PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)--at activating spikes in retinal ganglion cells in whole mount rat retina through stimulation of the local retinal network. Stimulation efficacy of the microelectrodes was analyzed by comparing voltage, current and transferred charge at stimulation threshold. Retinal ganglion cell spikes were recorded by a central electrode (30 μm diameter) in the planar grid of an electrode array. Extracellular stimulation (monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using constant voltage pulses applied to the eight surrounding electrodes. The stimulation electrodes were equally spaced on the four sides of a square (400 × 400 μm). Threshold voltage was determined as the pulse amplitude required to evoke network-mediated ganglion cell spiking in a defined post stimulus time window in 50% of identical stimulus repetitions. For the two electrode materials threshold voltage, transferred charge at threshold, maximum current and the residual current at the end of the pulse were compared. Stimulation of retinal interneurons using PEDOT-CNT electrodes is achieved with lower stimulation voltage and requires lower charge transfer as compared to TiN. The key parameter for effective stimulation is a constant current over at least 0.5 ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to its faradaic charge transfer mechanism. In neuroprosthetic implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a safe voltage regime and lower energy-consumption. Our study also indicates, that the charge transferred at threshold or the charge injection capacity per se does not determine stimulation efficacy.

  5. PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities

    Science.gov (United States)

    Samba, R.; Herrmann, T.; Zeck, G.

    2015-02-01

    Objective. The aim of this study was to compare two different microelectrode materials—the conductive polymer composite poly-3,4-ethylenedioxythiophene (PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)—at activating spikes in retinal ganglion cells in whole mount rat retina through stimulation of the local retinal network. Stimulation efficacy of the microelectrodes was analyzed by comparing voltage, current and transferred charge at stimulation threshold. Approach. Retinal ganglion cell spikes were recorded by a central electrode (30 μm diameter) in the planar grid of an electrode array. Extracellular stimulation (monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using constant voltage pulses applied to the eight surrounding electrodes. The stimulation electrodes were equally spaced on the four sides of a square (400 × 400 μm). Threshold voltage was determined as the pulse amplitude required to evoke network-mediated ganglion cell spiking in a defined post stimulus time window in 50% of identical stimulus repetitions. For the two electrode materials threshold voltage, transferred charge at threshold, maximum current and the residual current at the end of the pulse were compared. Main results. Stimulation of retinal interneurons using PEDOT-CNT electrodes is achieved with lower stimulation voltage and requires lower charge transfer as compared to TiN. The key parameter for effective stimulation is a constant current over at least 0.5 ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to its faradaic charge transfer mechanism. Significance. In neuroprosthetic implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a safe voltage regime and lower energy-consumption. Our study also indicates, that the charge transferred at threshold or the charge injection capacity per se does not determine stimulation efficacy.

  6. Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model in vivo.

    Science.gov (United States)

    Fransen, James W; Pangeni, Gobinda; Pardue, Machelle T; McCall, Maureen A

    2014-08-01

    In clinical trials, retinitis pigmentosa patients implanted with a retinal prosthetic device show enhanced spatial vision, including the ability to read large text and navigate. New prosthetics aim to increase spatial resolution by decreasing pixel/electrode size and limiting current spread. To examine spatial resolution of a new prosthetic design, we characterized and compared two photovoltaic array (PVA) designs and their interaction with the retina after subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3). PVAs were implanted subretinally at two stages of degeneration and assessed in vivo using extracellular recordings in the superior colliculus (SC). Several aspects of this interaction were evaluated by varying duration, irradiance and position of a near infrared laser focused on the PVA. These characteristics included: activation threshold, response linearity, SC signal topography and spatial localization. The major design difference between the two PVA designs is the inclusion of local current returns in the newer design. When tested in vivo, PVA-evoked response thresholds were independent of pixel/electrode size, but differ between the new and old PVA designs. Response thresholds were independent of implantation age and duration (⩽7.5 months). For both prosthesis designs, threshold intensities were within established safety limits. PVA-evoked responses require inner retina synaptic transmission and do not directly activate retinal ganglion cells. The new PVA design evokes local retinal activation, which is not found with the older PVA design that lacks local current returns. Our study provides in vivo evidence that prosthetics make functional contacts with the inner nuclear layer at several stages of degeneration. The new PVA design enhances local activation within the retina and SC. Together these results predict that the new design can potentially harness the inherent processing within the retina and is likely to produce higher

  7. In vitro biomechanical modulation--retinal detachment in a box.

    Science.gov (United States)

    Ghosh, Fredrik; Arnér, Karin; Taylor, Linnéa

    2016-03-01

    To illustrate the importance of biomechanical impact on tissue health within the central nervous system (CNS), we herein describe an in vitro model of rhegmatogenous retinal detachment (RRD) in which disruption and restoration of physical tissue support can be studied in isolation. Adult retinal porcine explants were kept in culture for 3 or 12 hours without any tissue support, simulating clinical RRD, after which they were either maintained in this state or reattached to the culture membrane for an additional 48 hours. In vitro detachment resulted in gliosis and severe progressive loss of retinal neurons. In contrast, if the explant was reattached, gliosis and overall cell death was attenuated, ganglion cell death was arrested, and the number of transducin-expressing cone photoreceptors increased. These results support the hypothesis that removal of the elastic retina from its normal physical environment results in degenerative damage, and, if restored, rescues retinal neurons. Our study reinforces the notion of a strong relationship between the biomechanical environment and homeostasis within the retina, which has significant bearing on pathologic events related to RRD, and may also have impact on other regions within the CNS under biomechanical influence.

  8. Macular retinal and choroidal thickness in unilateral amblyopia using swept-source optical coherence tomography.

    Science.gov (United States)

    Araki, Syunsuke; Miki, Atsushi; Goto, Katsutoshi; Yamashita, Tsutomu; Takizawa, Go; Haruishi, Kazuko; Ieki, Yoshiaki; Kiryu, Junichi; Yaoeda, Kiyoshi

    2017-09-15

    To investigate macular retinal and choroidal thickness in amblyopic eyes compared to that in fellow and normal eyes using swept-source optical coherence tomography (SS-OCT). This study examined 31 patients with hyperopic anisometropic amblyopia (6.9 ± 3.8 years, mean ± standard deviation), 15 patients with strabismic amblyopia without anisometropia (7.9 ± 4.2 years), and 24 age-matched controls (7.8 ± 3.3 years). Retinal and choroidal thickness was measured by 3D scans using SS-OCT. A 6-mm area around the fovea was automatically analyzed using the Early Treatment Diabetic Retinopathy Study map. The thickness from SS-OCT was corrected for magnification error using individual axial length, spherical refraction, cylinder refraction, and corneal radius. Retinal thickness was divided into the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL+IPL), ganglion cell complex (GCC), and the inner limiting membrane to the retinal pigment epithelium (ILM-RPE) thickness. Retinal and choroidal thickness was compared among amblyopic, fellow, and normal eyes. In both amblyopia groups, there was no significant difference in the mRNFL, GCL+IPL, and GCC thicknesses among the amblyopic, fellow, and control eyes. In the anisometropic amblyopia group, choroidal thickness (subfovea, center 1 mm, nasal and inferior of the inner ring, nasal of the outer ring, and center 6 mm) of amblyopic eyes were significantly greater than that of fellow and normal eyes. In contrast, none of the choroidal thicknesses were significantly different among the investigated eyes in the strabismic amblyopia group. We found no significant difference in inner retinal thickness in patients with unilateral amblyopia. Although there were significant differences in choroidal thickness with hyperopic anisometropic amblyopia, there was no significant difference for the strabismic amblyopia. The discrepancy in choroidal thickness between the two types of amblyopia may be due

  9. Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity.

    Science.gov (United States)

    Yamauchi, Mika; Tsuruma, Kazuhiro; Imai, Shunsuke; Nakanishi, Tomohiro; Umigai, Naofumi; Shimazawa, Masamitsu; Hara, Hideaki

    2011-01-10

    Crocetin is a carotenoid that is the aglicone of crocin, which are found in saffron stigmas (Crocus sativus L.) and gardenia fruit (Gardenia jasminoides Ellis). In this study, we investigated the effects of crocetin on retinal damage. To examine whether crocetin affects stress pathways, we investigated intracellular oxidation induced by reactive oxygen species, expression of endoplasmic reticulum (ER) stress-related proteins, disruption of the mitochondrial membrane potential (ΔΨ(m)), and caspases activation. In vitro, we employed cultured retinal ganglion cells (RGC-5, a mouse ganglion cell-line transformed using E1A virus). Cell damage was induced by tunicamycin or hydrogen peroxide (H(2)O(2)) exposure. Crocetin at a concentration of 3μM showed the inhibitory effect of 50-60% against tunicamycin- and H(2)O(2)-induced cell death and inhibited increase in caspase-3 and -9 activity. Moreover, crocetin inhibited the enzymatic activity of caspase-9 in a cell-free system. In vivo, retinal damage in mice was induced by exposure to white light at 8000lx for 3h after dark adaptation. Photoreceptor damage was evaluated by measuring the outer nuclear layer thickness at 5days after light exposure and recording the electroretinogram (ERG). Retinal cell damage was also detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at 48h after light exposure. Crocetin at 100mg/kg, p.o. significantly inhibited photoreceptor degeneration and retinal dysfunction and halved the expression of TUNEL-positive cells. These results indicate that crocetin has protective effects against retinal damage in vitro and in vivo, suggesting that the mechanism may inhibit increase in caspase-3 and -9 activities after retinal damage. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Subchondral synovial cysts (intra-osseous ganglion)

    International Nuclear Information System (INIS)

    Graf, L.; Freyschmidt, J.

    1988-01-01

    Twelve cases of subchondral synovial cysts (intra-osseous ganglion) have been seen and their clinical features, radiological findings and differential diagnosis are described. The lesion is a benign cystic tumour-like mass in the subchondral portion of a synovial joint. Our findings in respect of age, sex and localisation are compared with those of other authors. The aetiology and pathogenesis of the lesion is not completely understood. There is an increased incidence in middle life and joints with high dynamic and static stress are favoured, particularly in the lower extremities. Chronic stress or microtrauma, causing damage to the involved joint, therefore appears to be a plausible explanation. (orig.) [de

  11. Retinal profile and structural differences between myopes and emmetropes

    Science.gov (United States)

    Clark, Christopher Anderson

    Refractive development has been shown to be influenced by optical defocus in the eye and the interpretation of this signal appears to be localized in the retina. Optical defocus is not uniform across the retina and has been suggested as a potential cause of myopia development. Specifically hyperopic focus, i.e. focusing light behind the retina, may signal the eye to elongate, causing myopia. This non-uniform hyperopic signal appears to be due to the retinal shape. Ultimately, these signals are detected by the retina in an as yet undetermined manner. The purpose of this thesis is to examine the retinal profile using a novel method developed at Indiana University and then to examine retinal structural changes across the retina associated with myopia. Myopes exhibited more prolate retinas than hyperopes/emmetropes using the SD OCT. Using the SD OCT, this profile difference was detectable starting at 5 degrees from the fovea, which was closer than previously reported in the literature. These results agreed significantly with results found from peripheral refraction and peripheral axial length at 10 degrees. Overall, the total retina was thinner for myopes than hyperopes/emmetropes. It was also statistically significantly thinner for the Outer Nuclear Layer (ONL), Inner Nuclear Layer (INL) and Outer Plexiform Layer (OPL) but not for other retinal layers such as the Ganglion Layer. Thinning generally occurred outside of 5 degrees. The SD OCT method provided a nearly 10 fold increase in sensitivity which allowed for detection of profile changes closer to the fovea. The location of the retinal changes may be interesting as the layers that showed significant differences in thickness are also layers that contain cells believed to be associated with refractive development (amacrine, bipolar, and photoreceptor cells.) The reason for the retinal changes cannot be determined with this study, but possible theories include stretch due to axial elongation, neural remodeling due to

  12. Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities.

    Science.gov (United States)

    Mwachaka, Philip Maseghe; Saidi, Hassan; Odula, Paul Ochieng; Mandela, Pamela Idenya

    2015-01-01

    To describe the effect of monocular deprivation on densities of neural retinal cells in rabbits. Thirty rabbits, comprised of 18 subject and 12 control animals, were included and monocular deprivation was achieved through unilateral lid suturing in all subject animals. The rabbits were observed for three weeks. At the end of each week, 6 experimental and 3 control animals were euthanized, their retinas was harvested and processed for light microscopy. Photomicrographs of the retina were taken and imported into FIJI software for analysis. Neural retinal cell densities of deprived eyes were reduced along with increasing period of deprivation. The percentage of reductions were 60.9% (P < 0.001), 41.6% (P = 0.003), and 18.9% (P = 0.326) for ganglion, inner nuclear, and outer nuclear cells, respectively. In non-deprived eyes, cell densities in contrast were increased by 116% (P < 0.001), 52% (P < 0.001) and 59.6% (P < 0.001) in ganglion, inner nuclear, and outer nuclear cells, respectively. In this rabbit model, monocular deprivation resulted in activity-dependent changes in cell densities of the neural retina in favour of the non-deprived eye along with reduced cell densities in the deprived eye.

  13. Mouse ganglion-cell photoreceptors are driven by the most sensitive rod pathway and by both types of cones.

    Directory of Open Access Journals (Sweden)

    Shijun Weng

    Full Text Available Intrinsically photosensitive retinal ganglion cells (iprgcs are depolarized by light by two mechanisms: directly, through activation of their photopigment melanopsin; and indirectly through synaptic circuits driven by rods and cones. To learn more about the rod and cone circuits driving ipRGCs, we made multielectrode array (MEA and patch-clamp recordings in wildtype and genetically modified mice. Rod-driven ON inputs to ipRGCs proved to be as sensitive as any reaching the conventional ganglion cells. These signals presumably pass in part through the primary rod pathway, involving rod bipolar cells and AII amacrine cells coupled to ON cone bipolar cells through gap junctions. Consistent with this interpretation, the sensitive rod ON input to ipRGCs was eliminated by pharmacological or genetic disruption of gap junctions, as previously reported for conventional ganglion cells. A presumptive cone input was also detectable as a brisk, synaptically mediated ON response that persisted after disruption of rod ON pathways. This was roughly three log units less sensitive than the rod input. Spectral analysis revealed that both types of cones, the M- and S-cones, contribute to this response and that both cone types drive ON responses. This contrasts with the blue-OFF, yellow-ON chromatic opponency reported in primate ipRGCs. The cone-mediated response was surprisingly persistent during steady illumination, echoing the tonic nature of both the rod input to ipRGCs and their intrinsic, melanopsin-based phototransduction. These synaptic inputs greatly expand the dynamic range and spectral bandpass of the non-image-forming visual functions for which ipRGCs provide the principal retinal input.

  14. Anterior cruciate ligament ganglion: case report

    Directory of Open Access Journals (Sweden)

    André Pedrinelli

    Full Text Available CONTEXT: A ganglion is a cystic formation close to joints or tendinous sheaths, frequently found in the wrist, foot or knee. Intra-articular ganglia of the knee are rare, and most of them are located in the anterior cruciate ligament. The clinical picture for these ganglia comprises pain and movement restrictions in the knee, causing significant impairment to the patient. Symptoms are non-specific, and anterior cruciate ligament ganglia are usually diagnosed through magnetic resonance imaging or arthroscopy. Not all ganglia diagnosed through magnetic resonance imaging need to undergo surgical treatment: only those that cause clinical signs and symptoms do. Surgical results are considered good or excellent in the vast majority of cases. CASE REPORT: A 29-year-old male presented with pain in the left knee during a marathon race. Physical examination revealed limitation in the maximum range of knee extension and pain in the posterior aspect of the left knee. Radiographs of the left knee were normal, but magnetic resonance imaging revealed a multi-lobed cystic structure adjacent to the anterior cruciate ligament, which resembled a ganglion cyst. The mass was removed through arthroscopy, and pathological examination revealed a synovial cyst. Patient recovery was excellent, and he resumed his usual training routine five months later.

  15. Sciatica and claudication caused by ganglion cyst.

    Science.gov (United States)

    Yang, Guang; Wen, Xiaoyu; Gong, Yubao; Yang, Chen

    2013-12-15

    Case report. We report a rare case that a ganglion cyst compressed the sciatic nerve and caused sciatica and claudication in a 51-year-old male. Sciatica and claudication commonly occurs in spinal stenosis. To our knowledge, only 4 cases have been reported on sciatica resulting from posterior ganglion cyst of hip. A 51-year-old male had a 2-month history of radiating pain on his right leg. He could only walk 20 to 30 m before stopping and standing to rest for 1 to 3 minutes. Interestingly, he was able to walk longer distances (about 200 m) when walking slowly in small steps, without any rest. He had been treated as a case of lumbar disc herniation, but conservative treatment was ineffective. On buttock examination, a round, hard, and fixative mass was palpated at the exit of the sciatic nerve. MR imaging of hip revealed a multilocular cystic mass located on the posterior aspect of the superior gemellus and obturator internus, compressing the sciatic nerve. On operation, we found that the cyst extended to the superior gemellus and the obturator internus, positioned right at the outlet of the sciatic nerve. At 18 months of follow-up, the patient continued to be symptom free. He returned to comprehensive physical activity with no limitations. For an extraspinal source, a direct compression on the sciatic nerve also resulted in sciatica and claudication. A meticulous physical examination is very important for the differential diagnosis of extraspinal sciatica from spinal sciatica.

  16. Adaptive optics retinal imaging in the living mouse eye

    Science.gov (United States)

    Geng, Ying; Dubra, Alfredo; Yin, Lu; Merigan, William H.; Sharma, Robin; Libby, Richard T.; Williams, David R.

    2012-01-01

    Correction of the eye’s monochromatic aberrations using adaptive optics (AO) can improve the resolution of in vivo mouse retinal images [Biss et al., Opt. Lett. 32(6), 659 (2007) and Alt et al., Proc. SPIE 7550, 755019 (2010)], but previous attempts have been limited by poor spot quality in the Shack-Hartmann wavefront sensor (SHWS). Recent advances in mouse eye wavefront sensing using an adjustable focus beacon with an annular beam profile have improved the wavefront sensor spot quality [Geng et al., Biomed. Opt. Express 2(4), 717 (2011)], and we have incorporated them into a fluorescence adaptive optics scanning laser ophthalmoscope (AOSLO). The performance of the instrument was tested on the living mouse eye, and images of multiple retinal structures, including the photoreceptor mosaic, nerve fiber bundles, fine capillaries and fluorescently labeled ganglion cells were obtained. The in vivo transverse and axial resolutions of the fluorescence channel of the AOSLO were estimated from the full width half maximum (FWHM) of the line and point spread functions (LSF and PSF), and were found to be better than 0.79 μm ± 0.03 μm (STD)(45% wider than the diffraction limit) and 10.8 μm ± 0.7 μm (STD)(two times the diffraction limit), respectively. The axial positional accuracy was estimated to be 0.36 μm. This resolution and positional accuracy has allowed us to classify many ganglion cell types, such as bistratified ganglion cells, in vivo. PMID:22574260

  17. The retinal clock in mammals: role in health and disease

    Directory of Open Access Journals (Sweden)

    Felder-Schmittbuhl MP

    2017-05-01

    Full Text Available Marie-Paule Felder-Schmittbuhl,1,* Hugo Calligaro,2 Ouria Dkhissi-Benyahya2,* 1Institute of Cellular and Integratives Neurosciences, UPR3212, CNRS, Université de Strasbourg, Strasbourg, 2University of Lyon, Stem Cell and Brain Research Institute, INSERM U1208, Bron, France *These authors contributed equally to this work Abstract: The mammalian retina contains an extraordinary diversity of cell types that are highly organized into precise circuits to perceive and process visual information in a dynamic manner and transmit it to the brain. Above this builds up another level of complex dynamic, orchestrated by a circadian clock located within the retina, which allows retinal physiology, and hence visual function, to adapt to daily changes in light intensity. The mammalian retina is a remarkable model of circadian clock because it harbors photoreception, self-sustained oscillator function, and physiological outputs within the same tissue. However, the location of the retinal clock in mammals has been a matter of long debate. Current data have shown that clock properties are widely distributed among retinal cells and that the retina is composed of a network of circadian clocks located within distinct cellular layers. Nevertheless, the identity of the major pacemaker, if any, still warrants identification. In addition, the retina coordinates rhythmic behavior by providing visual input to the master hypothalamic circadian clock in the suprachiasmatic nuclei (SCN. This light entrainment of the SCN to the light/dark cycle involves a network of retinal photoreceptor cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs. Although it was considered that these photoreceptors synchronized both retinal and SCN clocks, new data challenge this view, suggesting that none of these photoreceptors is involved in photic entrainment of the retinal clock. Because circadian organization is a ubiquitous feature of the retina and controls

  18. The Role of Microglia and Peripheral Monocytes in Retinal Damage Following Corneal Chemical Injury.

    Science.gov (United States)

    Paschalis, Eleftherios I; Lei, Fengyang; Zhou, Chengxin; Kapoulea, Vassiliki; Thanos, Aristomenis; Dana, Reza; Vavvas, Demetrios; Chodosh, James; Dohlman, Claes H

    2018-04-06

    Eyes that have suffered alkali burn to the surface are excessively susceptible to subsequent severe glaucoma and retinal ganglion cell loss, despite maximal efforts to prevent or slow down the disease. Recently, we have shown in mice and rabbits, that such retinal damage is neither mediated by the alkali itself reaching the retina nor by intraocular pressure elevation. Rather, it is caused by the up-regulation of tumor necrosis factor alpha (TNF-α) that rapidly diffuses posteriorly, causing retinal ganglion cell apoptosis and CD45 + cell activation. Here, we investigated the involvement of peripheral blood monocytes and microglia in retinal damage. Using CX3CR1 +/EGFP ::CCR2 +/RFP reporter mice and bone marrow chimeras, we show that peripheral CX3CR1 + CD45 hi CD11b + MHC-II + monocyte infiltrate into the retina from the optic nerve at 24 hours after the burn and release further TNF-α. A secondary source of peripheral monocyte response originates from a rare population of 'patrolling' myeloid CCR2 + cells of the retina that differentiate into CX3CR1 + macrophages within hours after the injury. As a result, CX3CR1 + CD45 lo CD11b + microglia become reactive at 7 days, causing further TNF-α release. Prompt TNF-α inhibition after corneal burn suppresses monocyte infiltration and microglia activation, and protects the retina. This study may prove relevant to other injuries of the central nervous system. Copyright © 2018. Published by Elsevier Inc.

  19. Differential diagnosis of retinal vasculitis.

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; Herbort, Carl P; Tabbara, Khalid F

    2009-10-01

    Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings.

  20. Analysis the macular ganglion cell complex thickness in monocular strabismic amblyopia patients by Fourier-domain OCT

    Directory of Open Access Journals (Sweden)

    Hong-Wei Deng

    2014-11-01

    Full Text Available AIM: To detect the macular ganglion cell complex thickness in monocular strabismus amblyopia patients, in order to explore the relationship between the degree of amblyopia and retinal ganglion cell complex thickness, and found out whether there is abnormal macular ganglion cell structure in strabismic amblyopia. METHODS: Using a fourier-domain optical coherence tomography(FD-OCTinstrument iVue®(Optovue Inc, Fremont, CA, Macular ganglion cell complex(mGCCthickness was measured and statistical the relation rate with the best vision acuity correction was compared Gman among 26 patients(52 eyesincluded in this study. RESULTS: The mean thickness of the mGCC in macular was investigated into three parts: centrial, inner circle(3mmand outer circle(6mm. The mean thicknesses of mGCC in central, inner and outer circle was 50.74±21.51μm, 101.4±8.51μm, 114.2±9.455μm in the strabismic amblyopia eyes(SAE, and 43.79±11.92μm,92.47±25.01μm, 113.3±12.88μm in the contralateral sound eyes(CSErespectively. There was no statistically significant difference among the eyes(P>0.05. But the best corrected vision acuity had a good correlation rate between mGcc thicknesses, which was better relative for the lower part than the upper part.CONCLUSION:There is a relationship between the amblyopia vision acuity and the mGCC thickness. Although there has not statistically significant difference of the mGCC thickness compared with the SAE and CSE. To measure the macular center mGCC thickness in clinic may understand the degree of amblyopia.

  1. Laser speckle analysis of retinal vascular dynamics

    DEFF Research Database (Denmark)

    Neganova, Anastasiia Y.; Postnov, Dmitry D.; Jacobsen, Jens Christian B.

    2016-01-01

    -field laser speckle imaging to evaluate vascular responses of the retinal network. Image segmentation and vessel recognition algorithms together with response mapping allow us to analyze diameter changes and blood flow responses in the intact retinal network upon systemic administration of the vasoconstrictor......Studies of vascular responses are usually performed on isolated vessels or on single vessels in vivo. This allows for precise measurements of diameter or blood flow. However, dynamical responses of the whole microvascular network are difficult to access experimentally. We suggest to use full...

  2. Retinal specialisations in the dogfish Centroscymnus coelolepis from the Mediterranean deep-sea

    Directory of Open Access Journals (Sweden)

    Anna Bozzano

    2004-12-01

    Full Text Available The present work attempted to study the importance of vision in Centroscymnuscoelolepis, the most abundant shark in the Mediterranean beyond a depthof 1000 m, by using anatomical and histological data. C.coelolepis exhibited large lateral eyes with a large pupil, spherical lens and a tapetum lucidum that gave the eye a strong greenish-golden “eye shine”. In the outer retinal layer, a uniform population of rod-like photoreceptors was observed while in the vitreal retina a thick inner plexiform layer comprised up to 30% of the whole retinal thickness. The cell distribution of the ganglion cell layer formed a thin elongated visual streak in the central plane of the eye that provided a horizontal panoramic field of view. A specialised area of higher visual acuity was located caudally at 32-44º from the geometric centre of the retina and 5-10º above the horizontal plane of the eye. This position indicated that the visual axis pointed in a slightly outward-forward direction with respect to the fish body axis. A non-uniform distribution of large ganglion cells was also found in the horizontal plane of the retina that practically coincided with the distribution of the total cell population in the ganglion cell layer. This is the first time that this type of retinal specialisation has been observed in the elasmobranchs. These characteristics indicate that the retina of C.coelolepis is designed not only to increase sensitivity in the horizontal field of view, as was also observed in other sharks, but also to improve motion detection in the same plane. The visual capacities evolved by C.coelolepis make this species adapted for discriminating the horizontal gradation of light that exists in the mesopelagic environment. Similarly, the large ganglion cell distribution observed in its retina seems to be related to its predatory behaviour, since it allows this shark to perceive the movement of bioluminescent prey against a totally dark background.

  3. Retinal oximetry in patients with ischaemic retinal diseases

    DEFF Research Database (Denmark)

    Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob

    2017-01-01

    retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic...... retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO2 ) were associated with present as well as increasing levels of DR. Four of six studies also found...... whether retinal oximetry could be a potential tool for screening or a biomarker of treatment outcome in patients with ischaemic retinal diseases....

  4. The protective effect of prophylactic ozone administration against retinal ischemia-reperfusion injury.

    Science.gov (United States)

    Kal, Ali; Kal, Oznur; Akillioglu, Ishak; Celik, Esin; Yilmaz, Mustafa; Gonul, Saban; Solmaz, Merve; Onal, Ozkan

    2017-03-01

    Retinal ischemia-reperfusion (IR) injury is associated with many ocular diseases. Retinal IR injury leads to the death of retinal ganglion cells (RGCs), loss of retinal function and ultimately vision loss. The aim of this study was to show the protective effects of prophylactic ozone administration against retinal IR injury. A sham group (S) (n = 7) was administered physiological saline (PS) intraperitoneally (i.p.) for 7 d. An ischemia reperfusion (IR) group (n = 7) was subjected to retinal ischemia followed by reperfusion for 2 h. An ozone group (O) (n = 7) was administered 1 mg/kg of ozone i.p. for 7 d. In the ozone + IR (O + IR) group (n = 7), 1 mg/kg of ozone was administered i.p. for 7 d before the IR procedure and at 8 d, the IR injury was created (as in IR group). The rats were anesthetized after second hour of reperfusion and their intracardiac blood was drawn completely and they were sacrificed. Blood samples were sent to a laboratory for analysis of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total oxidant score (TOS) and total antioxidant capacity (TAC). The degree of retinal injury was evaluated according to changes in retinal cells and necrotic and apoptotic cells using the TUNEL method. Data were evaluated statistically with the Kruskal-Wallis test. The number of RGCs and the inner retinal thickness were significantly decreased after ischemia, and treatment with ozone significantly inhibited retinal ischemic injury. In the IR group, the degree of retinal injury was found to be the highest. In the O + IR group, retinal injury was found to be decreased in comparison to the IR group. In the ozone group without retinal IR injury, the retinal injury score was the lowest. The differences in the antioxidant parameters SOD, GSH-Px and TAC were increased in the ozone group and the lowest in the IR group. The oxidant parameters MDA and TOS were found to be the highest in the IR group and

  5. Retinal detachment repair

    Science.gov (United States)

    ... area (the macula). This can help prevent further detachment of the retina. It also will increase the chance of preserving ... buckling; Vitrectomy; Pneumatic retinopexy; Laser retinopexy; Rhegmatogenous retinal detachment repair Images ... detachment repair - series References Connolly BP, Regillo ...

  6. Learning about Retinitis Pigmentosa

    Science.gov (United States)

    ... visit NEI's Photos and Images page. Retina International [retina-international.org] Promotes the search for a treatment for RP, Usher Syndrome, macular degeneration and allied retinal dystrophies. RP International [rpinternational.org] ...

  7. Retinal artery occlusion

    Science.gov (United States)

    ... angiography Intraocular pressure Pupil reflex response Refraction Retinal photography Slit lamp examination Testing of side vision (visual ... In: Rakel RE, Rakel D, eds. Textbook of Family Medicine . 9th ed. Philadelphia, PA: Elsevier; 2016:chap ...

  8. Retinal vein occlusion

    Science.gov (United States)

    ... person's prescription for eyeglasses or contact lenses Retinal photography Slit lamp examination Testing of side vision (visual ... TR. Ophthalmology. In: Rakel RE, ed. Textbook of Family Medicine . 9th ed. Philadelphia, PA: Saunders Elsevier; 2016: ...

  9. Morphological patterns in children with ganglion related enteric neuronal abnormalities.

    Science.gov (United States)

    Henna, Nausheen; Nagi, Abdul H; Sheikh, Muhammad A; Shaukat, Mahmood

    2011-01-01

    Hirschsprung's Disease (HD) is a developmental disorder of enteric nervous system characterised by the absence of ganglion cells in submucosal (Meissner's) and myenteric (Aurbach's) plexuses of distal bowel. The purpose of the present study was to observe and report the morphological patterns of ganglion related enteric neuronal abnormalities in children presented with clinical features of (HD) in a Pakistani population. A total of 92 patients with clinical presentation of HD were enrolled between March 2009 and October 2009. Among them, 8 were excluded according to the exclusion criteria. After detailed history and physical examination, paraffin embedded H and E stained sections were prepared from the serial open biopsies from colorectum. The data was analysed using SPSS-17. Frequencies and percentages are given for qualitative variables. Non-parametric Binomial Chi-Square test was applied to observe within group associations and pganglionic whereas 71 (84.5%) showed ganglion related enteric neuronal abnormalities namely isolated hypoganglionosis 9 (12.7%), immaturity of ganglion cells 9 (12.7%), isolated hyperganglionosis (IND Type B) 2 (2.8%) and Hirschsprung's disease 51 (71.8%). Among HD group, 34 (66.7%) belonged to isolated form and 17 (33.3%) showed combined ganglion related abnormalities. Hirschsprung's disease is common in Pakistani population, followed by hypoganglionosis, immaturity of ganglion cells and IND type B. The presence of hypertrophic nerve fibres was significant in HD, hyperganglionosis and hypoganglionosis, whereas, no hypertrophic nerve fibres were appreciated in immaturity of ganglion cell group.

  10. Using Matrix and Tensor Factorizations for the Single-Trial Analysis of Population Spike Trains

    Science.gov (United States)

    Onken, Arno; Liu, Jian K.; Karunasekara, P. P. Chamanthi R.; Delis, Ioannis; Gollisch, Tim; Panzeri, Stefano

    2016-01-01

    Advances in neuronal recording techniques are leading to ever larger numbers of simultaneously monitored neurons. This poses the important analytical challenge of how to capture compactly all sensory information that neural population codes carry in their spatial dimension (differences in stimulus tuning across neurons at different locations), in their temporal dimension (temporal neural response variations), or in their combination (temporally coordinated neural population firing). Here we investigate the utility of tensor factorizations of population spike trains along space and time. These factorizations decompose a dataset of single-trial population spike trains into spatial firing patterns (combinations of neurons firing together), temporal firing patterns (temporal activation of these groups of neurons) and trial-dependent activation coefficients (strength of recruitment of such neural patterns on each trial). We validated various factorization methods on simulated data and on populations of ganglion cells simultaneously recorded in the salamander retina. We found that single-trial tensor space-by-time decompositions provided low-dimensional data-robust representations of spike trains that capture efficiently both their spatial and temporal information about sensory stimuli. Tensor decompositions with orthogonality constraints were the most efficient in extracting sensory information, whereas non-negative tensor decompositions worked well even on non-independent and overlapping spike patterns, and retrieved informative firing patterns expressed by the same population in response to novel stimuli. Our method showed that populations of retinal ganglion cells carried information in their spike timing on the ten-milliseconds-scale about spatial details of natural images. This information could not be recovered from the spike counts of these cells. First-spike latencies carried the majority of information provided by the whole spike train about fine-scale image

  11. Using Matrix and Tensor Factorizations for the Single-Trial Analysis of Population Spike Trains.

    Directory of Open Access Journals (Sweden)

    Arno Onken

    2016-11-01

    Full Text Available Advances in neuronal recording techniques are leading to ever larger numbers of simultaneously monitored neurons. This poses the important analytical challenge of how to capture compactly all sensory information that neural population codes carry in their spatial dimension (differences in stimulus tuning across neurons at different locations, in their temporal dimension (temporal neural response variations, or in their combination (temporally coordinated neural population firing. Here we investigate the utility of tensor factorizations of population spike trains along space and time. These factorizations decompose a dataset of single-trial population spike trains into spatial firing patterns (combinations of neurons firing together, temporal firing patterns (temporal activation of these groups of neurons and trial-dependent activation coefficients (strength of recruitment of such neural patterns on each trial. We validated various factorization methods on simulated data and on populations of ganglion cells simultaneously recorded in the salamander retina. We found that single-trial tensor space-by-time decompositions provided low-dimensional data-robust representations of spike trains that capture efficiently both their spatial and temporal information about sensory stimuli. Tensor decompositions with orthogonality constraints were the most efficient in extracting sensory information, whereas non-negative tensor decompositions worked well even on non-independent and overlapping spike patterns, and retrieved informative firing patterns expressed by the same population in response to novel stimuli. Our method showed that populations of retinal ganglion cells carried information in their spike timing on the ten-milliseconds-scale about spatial details of natural images. This information could not be recovered from the spike counts of these cells. First-spike latencies carried the majority of information provided by the whole spike train about fine

  12. [Progression of nerve fiber layer defects in retrobulbar optic neuritis by the macular ganglion cell complex].

    Science.gov (United States)

    Hong, D; Bosc, C; Chiambaretta, F

    2017-11-01

    Recent studies with SD OCT had shown early axonal damage to the macular ganglion cell complex (which consists of the three innermost layers of the retina: Inner Plexiform Layer [IPL], Ganglion Cell Layer [GCL], Retinal Nerve Fibre layer [RNFL]) in optic nerve pathology. Retrobulbar optic neuritis (RBON), occurring frequently in demyelinating diseases, leads to atrophy of the optic nerve fibers at the level of the ganglion cell axons, previously described in the literature. The goal of this study is to evaluate the progression of optic nerve fiber defects and macular ganglion cell complex defects with the SPECTRALIS OCT via a reproducible method by calculating a mean thickness in each quadrant after an episode of retrobulbar optic neuritis. This is a prospective monocentric observational study including 8 patients at the Clermont-Ferrand university medical center. All patients underwent ocular examination with macular and disc OCT analysis and a Goldmann visual field at the time of inclusion (onset or recurrence of RBON), at 3 months and at 6 months. Patients were 40-years-old on average at the time of inclusion. After 6 months of follow-up, there was progression of the atrophy of the macular ganglion cell complex in the affected eye on (11.5% or 11μm) predominantly inferonasally (13.9% or 16μm) and superonasally (12.9% or 14μm) while the other eye remained stable. The decrease in thickness occurred mainly in the most internal 3 layers of the retina. On average, the loss in thickness of the peripapillary RNFL was predominantly inferotemporal (24.9% or 39μm) and superotemporal (21.8% or 28μm). In 3 months of progression, the loss of optic nerve fibers is already seen on macular and disc OCT after an episode of RBON, especially in inferior quadrants in spite of the improvement in the Goldmann visual field and visual acuity. Segmentation by quadrant was used here to compare the progression of the defect by region compared to the fovea in a global and reproducible

  13. SOCS3 in retinal neurons and glial cells suppresses VEGF signaling to prevent pathological neovascular growth.

    Science.gov (United States)

    Sun, Ye; Ju, Meihua; Lin, Zhiqiang; Fredrick, Thomas W; Evans, Lucy P; Tian, Katherine T; Saba, Nicholas J; Morss, Peyton C; Pu, William T; Chen, Jing; Stahl, Andreas; Joyal, Jean-Sébastien; Smith, Lois E H

    2015-09-22

    Neurons and glial cells in the retina contribute to neovascularization, or the formation of abnormal new blood vessels, in proliferative retinopathy, a condition that can lead to vision loss or blindness. We identified a mechanism by which suppressor of cytokine signaling 3 (SOCS3) in neurons and glial cells prevents neovascularization. We found that Socs3 expression was increased in the retinal ganglion cell and inner nuclear layers after oxygen-induced retinopathy. Mice with Socs3 deficiency in neuronal and glial cells had substantially reduced vaso-obliterated retinal areas and increased pathological retinal neovascularization in response to oxygen-induced retinopathy, suggesting that loss of neuronal/glial SOCS3 increased both retinal vascular regrowth and pathological neovascularization. Furthermore, retinal expression of Vegfa (which encodes vascular endothelial growth factor A) was higher in these mice than in Socs3 flox/flox controls, indicating that neuronal and glial SOCS3 suppressed Vegfa expression during pathological conditions. Lack of neuronal and glial SOCS3 resulted in greater phosphorylation and activation of STAT3, which led to increased expression of its gene target Vegfa, and increased endothelial cell proliferation. In summary, SOCS3 in neurons and glial cells inhibited the STAT3-mediated secretion of VEGF from these cells, which suppresses endothelial cell activation, resulting in decreased endothelial cell proliferation and angiogenesis. These results suggest that neuronal and glial cell SOCS3 limits pathological retinal angiogenesis by suppressing VEGF signaling. Copyright © 2015, American Association for the Advancement of Science.

  14. Stellate ganglion blockade for analgesia following upper limb surgery.

    LENUS (Irish Health Repository)

    McDonnell, J G

    2012-01-31

    We report the successful use of a stellate ganglion block as part of a multi-modal postoperative analgesic regimen. Four patients scheduled for orthopaedic surgery following upper limb trauma underwent blockade of the stellate ganglion pre-operatively under ultrasound guidance. Patients reported excellent postoperative analgesia, with postoperative VAS pain scores between 0 and 2, and consumption of morphine in the first 24 h ranging from 0 to 14 mg. While these are preliminary findings, and must be confirmed in a clinical trial, they highlight the potential for stellate ganglion blockade to provide analgesia following major upper limb surgery.

  15. Visual advantage in deaf adults linked to retinal changes.

    Directory of Open Access Journals (Sweden)

    Charlotte Codina

    Full Text Available The altered sensory experience of profound early onset deafness provokes sometimes large scale neural reorganisations. In particular, auditory-visual cross-modal plasticity occurs, wherein redundant auditory cortex becomes recruited to vision. However, the effect of human deafness on neural structures involved in visual processing prior to the visual cortex has never been investigated, either in humans or animals. We investigated neural changes at the retina and optic nerve head in profoundly deaf (N = 14 and hearing (N = 15 adults using Optical Coherence Tomography (OCT, an in-vivo light interference method of quantifying retinal micro-structure. We compared retinal changes with behavioural results from the same deaf and hearing adults, measuring sensitivity in the peripheral visual field using Goldmann perimetry. Deaf adults had significantly larger neural rim areas, within the optic nerve head in comparison to hearing controls suggesting greater retinal ganglion cell number. Deaf adults also demonstrated significantly larger visual field areas (indicating greater peripheral sensitivity than controls. Furthermore, neural rim area was significantly correlated with visual field area in both deaf and hearing adults. Deaf adults also showed a significantly different pattern of retinal nerve fibre layer (RNFL distribution compared to controls. Significant correlations between the depth of the RNFL at the inferior-nasal peripapillary retina and the corresponding far temporal and superior temporal visual field areas (sensitivity were found. Our results show that cross-modal plasticity after early onset deafness may not be limited to the sensory cortices, noting specific retinal adaptations in early onset deaf adults which are significantly correlated with peripheral vision sensitivity.

  16. Retinal Detachment Due to Retinal Dialysis: Surgical Outcome After Scleral Buckling.

    Science.gov (United States)

    Jan, Sanaullah; Hussain, Zakir; Khan, Umer; Khan, Mohammad Tariq; Karim, Samina

    2015-01-01

    The aim of this study was to determine the efficacy and safety of scleral buckling surgery in retinal detachment due to retinal dialysis. This study was a prospective, interventional case series. A total of 48 eyes of 48 consecutive patients were included after obtaining informed written consent. Besides taking a thorough history, all eyes were examined by a retinal surgeon. The macula status, site, and extent of retinal dialysis and rhegmatogenous retinal detachment (RRD) were particularly noted. Proliferative vitreoretinopathy grading was done. Buckling was performed by a single surgeon. At every follow-up, visual acuity, intraocular pressure, retina status, and buckle position were noted. Any complication found was recorded. Follow-up was done for at least 6 months. SPSS version 16 was used for data analysis. We included 48 cases of RRD due to retinal dialysis. The mean ± SD age of the patients was 26.85 ± 15.1 years. The macula was detached in 85.4% of the cases, and proliferative vitreoretinopathy grade C was found in 25% of the cases. A surgical reattachment rate of 95.8% was attained after a single primary buckling procedure. Final Snellen best-corrected visual acuity of 6/18 or better was attained in 12.5% of the cases. However, 62.5% of the cases had best-corrected visual acuity in the range of 6/24 to 6/60. Subretinal hemorrhage occurred in 8.3% of cases intraoperatively after subretinal fluid drainage. We conclude that scleral buckling has a definite role in the management of RRD due to retinal dialysis.

  17. CNTF induces dose-dependent alterations in retinal morphology in normal and rcd-1 canine retina.

    Science.gov (United States)

    Zeiss, Caroline J; Allore, Heather G; Towle, Virginia; Tao, Weng

    2006-03-01

    Ciliary neurotrophic factor (CNTF) provides morphologic preservation of rods in several animal models of retinitis pigmentosa (RP). However, CNTF may alter photoreceptor morphology and rod photoreceptor differentiation in vitro, as well as affecting normal retinal electrophysiology. In addition, the capacity of CNTF to support other cell types affected secondarily in RP (cones and ganglion cells) is unclear. The purposes of this study were to examine the effects of CNTF upon a canine model of RP, the rod-cone degeneration (rcd-1) dog. Archival tissue from a previous study assessing the capacity of CNTF to rescue photoreceptors in rcd-1 dogs was used. One eye was treated for 7 weeks before being explanted. The contralateral eye was untreated. A total of 23 rcd-1 dogs and seven control dogs (four untreated and three CNTF-treated) were used. Morphometric data describing outer and inner nuclear layer thickness, inner retinal thickness, cones and ganglion cells were collected at nine evenly spaced points along each retina and analysed using a mixed effects model. Immunohistochemistry was performed on a subset of 11 dogs for expression of rhodopsin, human cone arrestin (hCAR) and recoverin. CNTF protected the outer nuclear layer and increased inner retinal thickness in a dose-dependent manner (both were maximal at CNTF doses of 1-6 ng day-1). Significant cone loss or reduction of inner nuclear layer width in rcd-1 did not occur in this model, therefore we were unable to assess the protective effect of CNTF upon these parameters. CNTF did not afford significant ganglion cell protection. CNTF induced morphologic changes in rods and ganglion cells, as well as reducing expression of hCAR and rhodopsin, but not recoverin. The dose of CNTF which provided optimal outer nuclear layer protection also resulted in several other effects, including altered ganglion cell morphology, increased thickness of the entire retina, and reduced expression of some phototransduction proteins

  18. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    Science.gov (United States)

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-08-10

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. 2016 BMJ Publishing Group Ltd.

  19. Thinning of Inner Retinal Layers after Vitrectomy with Silicone Oil versus Gas Endotamponade in Eyes with Macula-Off Retinal Detachment.

    Science.gov (United States)

    Purtskhvanidze, Konstantine; Hillenkamp, Jost; Tode, Jan; Junge, Olaf; Hedderich, Jürgen; Roider, Johann; Treumer, Felix

    2017-01-01

    To evaluate retinal layer thickness with optical coherence tomography (OCT) in eyes with macula-off retinal detachment after silicone oil (SiO) or gas endotamponade. Cross-sectional study of 40 eyes with macula-off rhegmatogenous retinal detachment that underwent vitrectomy. 20 eyes received SiO tamponade and 20 matched eyes received gas. 33 healthy fellow eyes served as controls. Macular spectral domain OCT was performed with automated layer detection in the 5 inner subfields of the Early Treatment Diabetic Retinopathy Study (ETDRS) map. Comparing the SiO group with the gas group, the ganglion cell layer showed a significant thinning in all fields of the inner ring of the ETDRS map, the inner plexiform layer in the nasal, superior and temporal quadrants, and the outer plexiform layer in the nasal quadrant. Inner retinal layers in the fovea/parafovea were significantly thinner in the SiO group. Prospective studies are warranted to further elucidate possible retinal adverse effects of SiO tamponade. © 2017 S. Karger AG, Basel.

  20. CT brain demonstration of basal ganglion calcification in adult HIV ...

    African Journals Online (AJOL)

    brain barrier has been postulated. Calcification of the basal ganglia in encephalopathic HIV/AIDS children has been relatively well documented. Only two adult HIV cases with basal ganglion calcification (BGC) have been reported in the literature.

  1. Evaluation of new approach to ultrasound guided stellate ganglion block

    Directory of Open Access Journals (Sweden)

    Anju Ghai

    2016-01-01

    Conclusion: There is a significant variation in the anatomy of stellate ganglion at the level of C 6 and C 7 . Ultrasound guided lateral approach increases the efficacy of SGB by deposition of drug subfascially with real-time imaging.

  2. Melatonin: An Underappreciated Player in Retinal Physiology and Pathophysiology

    Science.gov (United States)

    Tosini, Gianluca; Baba, Kenkichi; Hwang, Christopher K.; Iuvone, P. Michael

    2012-01-01

    In the vertebrate retina, melatonin is synthesized by the photoreceptors with high levels of melatonin at night and lower levels during the day. Melatonin exerts its influence by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylyl cyclase. Melatonin receptors belonging to the subtypes MT1 and MT2 have been identified in the mammalian retina. MT1 and MT2 receptors are found in all layers of the neural retina and in the retinal pigmented epithelium. Melatonin in the eye is believed to be involved in the modulation of many important retinal functions; it can modulate the electroretinogram (ERG), and administration of exogenous melatonin increases light-induced photoreceptor degeneration. Melatonin may also have protective effects on retinal pigment epithelial cells, photoreceptors and ganglion cells. A series of studies have implicated melatonin in the pathogenesis of age-related macular degeneration, and melatonin administration may represent a useful approach to prevent and treat glaucoma. Melatonin is used by millions of people around the world to retard aging, improve sleep performance, mitigate jet lag symptoms, and treat depression. Administration of exogenous melatonin at night may also be beneficial for ocular health, but additional investigation is needed to establish its potential. PMID:22960156

  3. Rhegmatogenous retinal detachment and uveitis.

    Science.gov (United States)

    Kerkhoff, Frank T; Lamberts, Querin J; van den Biesen, Pieter R; Rothova, Aniki

    2003-02-01

    To evaluate the frequency, high-risk factors, and visual prognosis of rhegmatogenous retinal detachment (RRD) in patients with uveitis. Retrospective case-control study. We included 1387 consecutive patients with uveitis who consulted our uveitis clinic from January 1990 through December 1997 of whom 43 patients (46 eyes) with RRD were identified. The retinal detachment (RD) controls were 212 consecutive patients with RRD (221 eyes, first occurrence of RD, not associated with uveitis) who were admitted for surgery in the period from April 1999 to April 2000. The uveitis control group consisted of 150 age-matched patients (210 eyes) selected from the entire uveitis series. Retrospective analysis of clinical data. The presence of RRD and eventual risk factors for RRD, such as myopia, retinal lattice degeneration, prior intraocular surgery, anatomic location of uveitis, its specific diagnosis, and clinical manifestations. Furthermore, the surgical and nonsurgical outcomes of RRD, as well as the results of various treatment regimens, were analyzed. RRD was identified in 3.1% of the patients with uveitis. RRD was most frequently associated with panuveitis (6.6%). RRD was associated more frequently with infectious (7.6%) than noninfectious uveitis (2.1%). At the onset of RRD, uveitis was active in most (46%) affected eyes. Proliferative vitreoretinopathy was present in 30% of the uveitic RRD eyes at presentation in contrast to 12% of the RRD control eyes. In uveitic RRD, the retina was reattached in 59% of eyes with a single operation; the final anatomic reattachment rate was 88%. Finally, a visual acuity of less than 20/200 was present in 71% of the uveitic RRD eyes, 10% of which had no light perception. We discovered a high prevalence of RRD in patients with active panuveitis and infectious uveitis and document that uveitis in itself is a risk factor for the development of RRD. The visual prognosis of RRD in uveitis was poor because of the uveitis itself and the

  4. Recurrence of a Periosteal Ganglion in the Tibia

    Directory of Open Access Journals (Sweden)

    Ka-Kin Samuel Ling

    2013-12-01

    Full Text Available Periosteal ganglion is a rare type of ganglia most commonly located in the tibia. The clinical outcomes after surgical excision have not been documented in literature. We report a case of a periosteal ganglion in the proximal tibia with repeated recurrences despite surgical excisions. Magnetic resonance imaging (MRI, contrast arthrogram, and arthroscopy may have their values, especially for the detection of intra-articular communication in juxta-articular lesions.

  5. Spontaneous activity in the statoacoustic ganglion of the chicken embryo.

    Science.gov (United States)

    Jones, T A; Jones, S M

    2000-03-01

    Statoacoustic ganglion cells in the mature bird include neurons that are responsive to sound (auditory) and those that are not (nonauditory). Those that are nonauditory have been shown to innervate an otolith organ, the macula lagena, whereas auditory neurons innervate the basilar papilla. In the present study, single-unit recordings of statoacoustic ganglion cells were made in embryonic (E19, mean = 19.2 days of incubation) and hatchling (P6-P14, mean = 8.6 days posthatch) chickens. Spontaneous activity from the two age groups was compared with developmental changes. Activity was evaluated for 47 auditory, 11 nonauditory, and 6 undefined eighth nerve neurons in embryos and 29 auditory, 26 nonauditory, and 1 undefined neurons in hatchlings. For auditory neurons, spontaneous activity displayed an irregular pattern [discharge interval coefficient of variation (CV) was >0.5, mean CV for embryos was 1.46 +/- 0.58 and for hatchlings was 1.02 +/- 0.25; means +/- SD]. Embryonic discharge rates ranged from 0.05 to 97.6 spikes per second (sp/s) for all neurons (mean 18.6 +/- 16.9 sp/s). Hatchling spontaneous rates ranged from 1.2 to 185.2 sp/s (mean 66.5 +/- 39.6 sp/s). Discharge rates were significantly higher for hatchlings (P embryonic auditory neurons displayed long silent periods between irregular bursts of neural activity, a feature not seen posthatch. All regular bursting discharge patterns were correlated with heart rate in both embryos and hatchlings. Preferred intervals were visible in the time interval histograms (TIHs) of only one embryonic neuron in contrast to 55% of the neurons in posthatch animals. Generally, the embryonic auditory TIH displayed a modified quasi-Poisson distribution. Nonauditory units generally displayed regular (CV 0.5) activity and Gaussian and modified-Gaussian TIHs. Long silent periods or bursting patterns were not a characteristic of embryonic nonauditory neurons. CV varied systematically as a function of discharge rate in nonauditory

  6. Retinal shows its true colours

    DEFF Research Database (Denmark)

    Coughlan, N. J.A.; Adamson, B. D.; Gamon, L.

    2015-01-01

    Retinal is one of Nature's most important and widespread chromophores, exhibiting remarkable versatility in its function and spectral response, depending on its protein environment. Reliable spectroscopic and photochemical data for the isolated retinal molecule are essential for calibrating theor...

  7. The effects of temperature changes on retinal ganglion cell responses to electrical stimulation.

    Science.gov (United States)

    Maturana, Matias I; Apollo, Nicholas V; Garrett, David J; Kameneva, Tatiana; Meffin, Hamish; Ibbotson, Michael R; Cloherty, Shaun L; Grayden, David B

    2015-01-01

    Little is known about how the retina's response to electrical stimulation is modified by temperatures. In vitro experiments are often used to inform in vivo studies, hence it is important to understand what changes occur at physiological temperature. To investigate this, we recorded from eight RGCs in vitro at three temperatures; room temperature (24°C), 30°C and 34°C. Results show that response latencies and thresholds are reduced, bursting spike rates in response to stimulation increases, and the spiking becomes more consistently locked to the stimulus at higher temperatures.

  8. Sensitivity of Retinal Ganglion Cell Photoreceptors in Traumatic Brain Injury Patients with Photophobia

    Science.gov (United States)

    2015-11-01

    significant difference in the pupil response to monochrome flickering stimuli (red or blue light only), presented after dark adaptation, in the two...regarding the amount of light present in the environment. ipRGCs are particularly sensitive to blue light and their responses typically persist for...with a relatively bright blue light , relative to that for comparable red light. Our guiding hypothesis for this research was that ipRGCs respond

  9. Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro

    DEFF Research Database (Denmark)

    Martins, João; Elvas, Filipe; Brudzewsky, Dan

    2015-01-01

    -reperfusion injury, pretreatment with NPY or (Leu31, Pro34)-NPY was not able to prevent apoptosis or rescue RGCs. In conclusion, we found modulatory effects of NPY application that for the first time were detected at the level of RGCs. However, further studies are needed to evaluate whether NPY neuroprotective...

  10. GAP-43 expression is upregulated in retinal ganglion cells after ischemia/reperfusion-induced damage

    NARCIS (Netherlands)

    Dijk, Frederike; Bergen, Arthur A. B.; Kamphuis, Willem

    2007-01-01

    In response to injury, the adult mammalian retina shows signs of structural remodeling, possibly in an attempt to preserve or regain some of its functional neural connections. In order to study the mechanisms involved in injury-induced plasticity, we have studied changes in growth associated protein

  11. Melanopsin-expressing retinal ganglion cells are resistant to cell injury, but not always

    DEFF Research Database (Denmark)

    Georg, Birgitte; Ghelli, Anna; Giordano, Carla

    2017-01-01

    Atrophy). However, these cells are affected in other neurodegenerative conditions, such as glaucoma and Alzheimer's disease. We here review the current evidences that may underlie this dichotomy. We also present our unpublished data on cell experiments demonstrating that melanopsin itself does not explain...

  12. Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity

    Science.gov (United States)

    El-Remessy, Azza B.; Khalil, Ibrahim E.; Matragoon, Suraporn; Abou-Mohamed, Gamal; Tsai, Nai-Jer; Roon, Penny; Caldwell, Ruth B.; Caldwell, Robert W.; Green, Keith; Liou, Gregory I.

    2003-01-01

    In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death. In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation. Excitotoxicity of the retina was induced by intravitreal injection of N-methyl-d-aspartate (NMDA) in rats, which also received 4-hydroxy-2,2,6,6-tetramethylpiperidine-n-oxyl (TEMPOL,a superoxide dismutase-mimetic), N-ω-nitro-l-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), THC, or CBD. Retinal neuron loss was determined by TDT-mediated dUTP nick-end labeling assay, inner retinal thickness, and quantification of the mRNAs of ganglion cell markers. NMDA induced a dose- and time-dependent accumulation of nitrite/nitrate, lipid peroxidation, and nitrotyrosine (foot print of peroxynitrite), and a dose-dependent apoptosis and loss of inner retinal neurons. Treatment with L-NAME or TEMPOL protected retinal neurons and confirmed the involvement of peroxynitrite in retinal neurotoxicity. The neuroprotection by THC and CBD was because of attenuation of peroxynitrite. The effect of THC was in part mediated by the cannabinoid receptor CB1. These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma. PMID:14578199

  13. TWENTY-FIVE-GAUGE PARS PLANA VITRECTOMY IN COMPLEX RETINAL DETACHMENTS ASSOCIATED WITH GIANT RETINAL TEAR.

    Science.gov (United States)

    Kumar, Vinod; Kumawat, Devesh; Bhari, Anju; Chandra, Parijat

    2018-04-01

    To study the structural and functional outcomes of 25-gauge pars plana vitrectomy in giant retinal tear-associated retinal detachments. Seventeen eyes of 17 patients with giant retinal tear, who underwent 25-gauge pars plana vitrectomy over a period of 15 months at a tertiary eye care center by a single surgeon, were recruited in this retrospective interventional study. Giant retinal tears were mostly traumatic (35.3%) or associated with myopia (35.3%) and occurred in young (mean age 25.7 years) males (94.1%). Most eyes had best-corrected visual acuity ≤20/1,200 (in 82.3%), foveal detachment (in 88.2%), and proliferative vitreoretinopathy ≤Grade B (in 82.3%). The giant retinal tear extent was more than 180° in 29.4% and the fellow eye was involved in 35.2% of eyes. All eyes underwent 25-gauge pars plana vitrectomy with encircling band in 41.1%, perfluorocarbon liquid use in 82.3%, and endotamponade with sulphur hexafluoride (23.6%) or silicone oil (76.4%). At mean follow-up of 10.2 months, reattachment rate was 88.2%. Only 35.2% of eyes achieved final visual acuity ≥20/80 with a cause of poor vision being cataract, secondary glaucoma, macular pucker, and corneal edema. Twenty-five-gauge pars plana vitrectomy can achieve excellent attachment rates in eyes with giant retinal tear-associated retinal detachment. It can be as efficient as larger-gauge vitrectomy, at the same time retaining all advantages of smaller-gauge surgery.

  14. Matrix metalloproteinase 14 in the zebrafish: an eye on retinal and retinotectal development.

    Directory of Open Access Journals (Sweden)

    Els Janssens

    Full Text Available Matrix metalloproteinases (MMPs are members of the metzincin superfamily of proteinases that cleave structural elements of the extracellular matrix and many molecules involved in signal transduction. Although there is evidence that MMPs promote the proper development of retinotectal projections, the nature and working mechanisms of specific MMPs in retinal development remain to be elucidated. Here, we report a role for zebrafish Mmp14a, one of the two zebrafish paralogs of human MMP14, in retinal neurogenesis and retinotectal development.Whole mount in situ hybridization and immunohistochemical stainings for Mmp14a in developing zebrafish embryos reveal expression in the optic tectum, in the optic nerve and in defined retinal cell populations, including retinal ganglion cells (RGCs. Furthermore, Mmp14a loss-of-function results in perturbed retinoblast cell cycle kinetics and consequently, in a delayed retinal neurogenesis, differentiation and lamination. These Mmp14a-dependent retinal defects lead to microphthalmia and a significantly reduced innervation of the optic tectum (OT by RGC axons. Mmp14b, on the contrary, does not appear to alter retinal neurogenesis or OT innervation. As mammalian MMP14 is known to act as an efficient MMP2-activator, we also explored and found a functional link and a possible co-involvement of Mmp2 and Mmp14a in zebrafish retinotectal development.Both the Mmp14a expression in the developing visual system and the Mmp14a loss-of-function phenotype illustrate a critical role for Mmp14a activity in retinal and retinotectal development.

  15. Retinal Detachment in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Prado Renata Silva do

    2002-01-01

    Full Text Available Preeclampsia is an obstetric disease of unknown cause that affects approximately 5% of pregnant women. The visual system may be affected with variable intensity, being the retinal detachment a rare complication. The retinal detachment in preeclampsia is usually bilateral and serous, and its pathogenesis is related to the choroidal ischemia secondary to an intense arteriolar vasospasm. The majority of patients have complete recovery of vision with clinical management, and surgery is unnecessary. This is a case report of a 27 year old patient who developed the severe form of preeclampsia on her first pregnancy. She had progressive blurred vision, until she could see only shadows. Ophthalmic examination diagnosed spread and bilateral retinal detachment. With blood pressure control at postpartum, the patient had her retina reattached, and recovery of vision.

  16. Bioelectronic retinal prosthesis

    Science.gov (United States)

    Weiland, James D.

    2016-05-01

    Retinal prosthesis have been translated to clinical use over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa and one device is in clinical trials for treatment of age-related macular degeneration. These devices provide partial sight restoration and patients use this improved vision in their everyday lives to navigate and to detect large objects. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. In particular, current retinal prostheses do not provide peripheral visions due to technical and surgical limitations, thus limiting the effectiveness of the treatment. This paper reviews recent results from human implant patients and presents technical approaches for peripheral vision.

  17. [Retinal pneumopexy in the treatment of rhegmatogenous retinal detachment].

    Science.gov (United States)

    Levai, L; Gavriş, Monica; Gábor, Radó; Bagosi, P

    2014-01-01

    To evaluate the efficiency of retinal pneumopexy in patients with rhegmatogenous retinal detachment. This clinical prospective study unrolled between november 2010-june 2012 in the Ophthalmology Department of the Military Hospital in Cluj-Napoca and Satu Mare Emergency Hospital included 20 patients (20 eyes) with rhegmatogenous retinal detachment. Patients were treated with retinal pneumopexy followed by laser photocoagulation. Anatomical and functional results were evaluated 1, 3, 6, 12 and 19 months after treatment. In 17 eyes out of 20, we achieved retinal reattachment and visual recovery. Three cases yelded no success, these being further treated with posterior vitrectomy. Retinal pneumopexy is a minimally invasive treatment method of rhegmatogenous retinal detachment with very good results in well selected cases.

  18. Contrast sensitivity, ocular blood flow and their potential role in assessing ischaemic retinal disease.

    Science.gov (United States)

    Shoshani, Yochai Z; Harris, Alon; Rusia, Deepam; Spaeth, George L; Siesky, Brent; Pollack, Ayala; Wirostko, Barbara

    2011-08-01

    To examine the definition, evaluation methodology, association to ocular blood flow and potential clinical value of contrast sensitivity (CS) testing in clinical and research settings, focusing in patients with ischemic retinal disease. A review of the medical literature focusing on CS and ocular blood flow in ischemic retinal disease. CS may be more sensitive than other methods at detecting subtle defects or improvements in primarily central retinal ganglion cell function early on in a disease process. CS testing attempts to provide spatial detection differences which are not directly assessed with standard visual acuity chart testing. Analyzing all studies that have assessed both CS change and ocular blood flow, it is apparent that both choroidal circulation and retinal circulation may have an important role in influencing CS. The concept that CS is directly influenced by ocular blood flow is supported by reviewing the studies involving both. Although the studies in the literature have not established a direct cause and effect relationship per se, the literature review makes it logical to assume that changes in retinal and choroidal blood flow influence CS. This raises the possibility that a subjective visual characteristic, specifically CS, may be able to be evaluated more objectively by studying blood flow. It appears appropriate to study the relationship between blood flow and CS more extensively to develop improved ways of measuring various aspects of blood flow to the eye and to best quantify early changes in visual function. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

  19. Deep Learning Models of the Retinal Response to Natural Scenes.

    Science.gov (United States)

    McIntosh, Lane T; Maheswaranathan, Niru; Nayebi, Aran; Ganguli, Surya; Baccus, Stephen A

    2016-01-01

    A central challenge in sensory neuroscience is to understand neural computations and circuit mechanisms that underlie the encoding of ethologically relevant, natural stimuli. In multilayered neural circuits, nonlinear processes such as synaptic transmission and spiking dynamics present a significant obstacle to the creation of accurate computational models of responses to natural stimuli. Here we demonstrate that deep convolutional neural networks (CNNs) capture retinal responses to natural scenes nearly to within the variability of a cell's response, and are markedly more accurate than linear-nonlinear (LN) models and Generalized Linear Models (GLMs). Moreover, we find two additional surprising properties of CNNs: they are less susceptible to overfitting than their LN counterparts when trained on small amounts of data, and generalize better when tested on stimuli drawn from a different distribution (e.g. between natural scenes and white noise). An examination of the learned CNNs reveals several properties. First, a richer set of feature maps is necessary for predicting the responses to natural scenes compared to white noise. Second, temporally precise responses to slowly varying inputs originate from feedforward inhibition, similar to known retinal mechanisms. Third, the injection of latent noise sources in intermediate layers enables our model to capture the sub-Poisson spiking variability observed in retinal ganglion cells. Fourth, augmenting our CNNs with recurrent lateral connections enables them to capture contrast adaptation as an emergent property of accurately describing retinal responses to natural scenes. These methods can be readily generalized to other sensory modalities and stimulus ensembles. Overall, this work demonstrates that CNNs not only accurately capture sensory circuit responses to natural scenes, but also can yield information about the circuit's internal structure and function.

  20. Eye Morphology and Retinal Topography in Hummingbirds (Trochilidae: Aves).

    Science.gov (United States)

    Lisney, Thomas J; Wylie, Douglas R; Kolominsky, Jeffrey; Iwaniuk, Andrew N

    2015-01-01

    Hummingbirds are a group of small, highly specialized birds that display a range of adaptations to their nectarivorous lifestyle. Vision plays a key role in hummingbird feeding and hovering behaviours, yet very little is known about the visual systems of these birds. In this study, we measured eye morphology in 5 hummingbird species. For 2 of these species, we used stereology and retinal whole mounts to study the topographic distribution of neurons in the ganglion cell layer. Eye morphology (expressed as the ratio of corneal diameter to eye transverse diameter) was similar among all 5 species and was within the range previously documented for diurnal birds. Retinal topography was similar in Amazilia tzacatl and Calypte anna. Both species had 2 specialized retinal regions of high neuron density: a central region located slightly dorso-nasal to the superior pole of the pecten, where densities reached ∼ 45,000 cells · mm(-2), and a temporal area with lower densities (38,000-39,000 cells · mm(-2)). A weak visual streak bridged the two high-density areas. A retina from Phaethornis superciliosus also had a central high-density area with a similar peak neuron density. Estimates of spatial resolving power for all 3 species were similar, at approximately 5-6 cycles · degree(-1). Retinal cross sections confirmed that the central high-density region in C. anna contains a fovea, but not the temporal area. We found no evidence of a second, less well-developed fovea located close to the temporal retina margin. The central and temporal areas of high neuron density allow for increased spatial resolution in the lateral and frontal visual fields, respectively. Increased resolution in the frontal field in particular may be important for mediating feeding behaviors such as aerial docking with flowers and catching small insects. © 2015 S. Karger AG, Basel.

  1. Nanomaterials and Retinal Toxicity

    Science.gov (United States)

    The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra­ vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...

  2. Protection of retinal function by sulforaphane following retinal ischemic injury.

    Science.gov (United States)

    Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

    2015-09-01

    Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Oxidative Stress in Retinal Muller Cells contributes to Dysfunction of Retinal Glutamate Uptake and Altered Protein Expression

    DEFF Research Database (Denmark)

    Toft-Kehler, Anne Katrine; Skytt, Dorte Marie; Kolko, Miriam

    2015-01-01

    Purpose: The viability of retinal ganglion cells (RGC) is essential to maintain the neuronal function of the retina. Müller cells (MC) are assumed to be vital in neuroprotection of the RGC. In this study, we evaluate the ability of oxidative stressed and energy restricted MC to remove glutamate...... from the extracellular space and evaluate related changes in gene and protein expressions. Methods: The human Müller glial cell line, MIO-M1, kindly provided by Astrid Limb, was used in all experiments. Changes in glutamate uptake were evaluated by kinetic uptake studies using 3H......-L-glutamate in oxidative stressed MC. The cell viability and mitochondrial function were evaluated by LDH and MTT assays, respectively. The expression of glutamate receptors as well as apoptotic and oxidative stress genes were evaluated by qPCR. By means of Western blot analysis the gene regulations were confirmed...

  4. Acute retinal ischemia caused by controlled low ocular perfusion pressure in a porcine model. Electrophysiological and histological characterisation

    DEFF Research Database (Denmark)

    Kyhn, Maria Voss; Warfvinge, Karin; Scherfig, Erik

    2009-01-01

    The purpose of this study was to establish, and characterize a porcine model of acute, controlled retinal ischemia. The controlled retinal ischemia was produced by clamping the ocular perfusion pressure (OPP) in the left eye to 5 mm Hg for 2 h. The OPP was defined as mean arterial blood pressure...... of the amplitudes obtained in the experimental, left eye, and the control, right eye. Quantitative histology was performed to measure the survival of ganglion cells, amacrine cells and horizontal cells 2-6 weeks after the ischemic insult. An OPP of 5 mm Hg for 2h induced significant reductions in the amplitudes...... the ischemic insult. This model seems to be suitable for investigations of therapeutic initiatives in diseases involving acute retinal ischemia....

  5. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeoun-Hee [Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Chang, Yongmin [Department of Molecular Medicine, Kyungpook National University College of Medicine, Kyungpook National University, 200 Dongduk-Ro Jung-Gu, Daegu 700-714 (Korea, Republic of); Jung, Jae-Chang, E-mail: jcjung@knu.ac.kr [Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. Black-Right-Pointing-Pointer Staurosporine mediates uPA activation during RGC differentiation in vitro. Black-Right-Pointing-Pointer Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. Black-Right-Pointing-Pointer Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that

  6. Peripheral retinal degenerations and the risk of retinal detachment.

    Science.gov (United States)

    Lewis, Hilel

    2003-07-01

    To review the degenerative diseases of the peripheral retina in relationship with the risk to develop a rhegmatogenous retinal detachment and to present recommendations for use in eyes at increased risk of developing a retinal detachment. Focused literature review and author's clinical experience. Retinal degenerations are common lesions involving the peripheral retina, and most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and, rarely, zonular traction tufts, can result in a rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic therapy; however, adequate studies have not been performed to date. Well-designed, prospective, randomized clinical studies are necessary to determine the benefit-risk ratio of prophylactic treatment. In the meantime, the evidence available suggests that most of the peripheral retinal degenerations should not be treated except in rare, high-risk situations.

  7. The Structure and Function of the Macula in Patients with Advanced Retinitis Pigmentosa

    Science.gov (United States)

    Vámos, Rita; Tátrai, Erika; Németh, János; Holder, Graham E.; DeBuc, Delia Cabrera

    2011-01-01

    Purpose. To assess the structure and function of the macula in advanced retinitis pigmentosa (RP). Methods. Twenty-nine eyes of 22 patients with RP were compared against 17 control eyes. Time-domain optical coherence tomography (OCT) data were processed using OCTRIMA (optical coherence tomography retinal image analysis) as a means of quantifying commercial OCT system images. The thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer and outer plexiform layer complex (INL+OPL), and the outer nuclear layer (ONL) were measured. Multifocal electroretinography (mfERG) was performed; two groups were formed based on the mfERG findings. Fourteen eyes had no detectable central retinal function (NCRF) on mfERG; detectable but abnormal retinal function (DRF) was present in the mfERG of the other 15 eyes. Results. The thickness of the ONL in the central macular region was significantly less in the NCRF eyes compared with that in both DRF eyes and controls. The ONL was significantly thinner in the pericentral region in both patient groups compared with that in controls, whereas the thickness of the GCL+IPL and INL+OPL was significantly decreased only in the NCRF eyes. The RNFL in the peripheral region was significantly thicker, whereas the thickness of the GCL+IPL and ONL was significantly thinner in both patient groups compared with that in controls. Conclusions. The results are consistent with degeneration of the outer retina preceding inner retinal changes in RP. OCT image segmentation enables objective evaluation of retinal structural changes in RP, with potential use in the planning of therapeutic interventions and conceivably as an outcome measure. PMID:21948552

  8. Automated segmentation by pixel classification of retinal layers in ophthalmic OCT images.

    Science.gov (United States)

    Vermeer, K A; van der Schoot, J; Lemij, H G; de Boer, J F

    2011-06-01

    Current OCT devices provide three-dimensional (3D) in-vivo images of the human retina. The resulting very large data sets are difficult to manually assess. Automated segmentation is required to automatically process the data and produce images that are clinically useful and easy to interpret. In this paper, we present a method to segment the retinal layers in these images. Instead of using complex heuristics to define each layer, simple features are defined and machine learning classifiers are trained based on manually labeled examples. When applied to new data, these classifiers produce labels for every pixel. After regularization of the 3D labeled volume to produce a surface, this results in consistent, three-dimensionally segmented layers that match known retinal morphology. Six labels were defined, corresponding to the following layers: Vitreous, retinal nerve fiber layer (RNFL), ganglion cell layer & inner plexiform layer, inner nuclear layer & outer plexiform layer, photoreceptors & retinal pigment epithelium and choroid. For both normal and glaucomatous eyes that were imaged with a Spectralis (Heidelberg Engineering) OCT system, the five resulting interfaces were compared between automatic and manual segmentation. RMS errors for the top and bottom of the retina were between 4 and 6 μm, while the errors for intra-retinal interfaces were between 6 and 15 μm. The resulting total retinal thickness maps corresponded with known retinal morphology. RNFL thickness maps were compared to GDx (Carl Zeiss Meditec) thickness maps. Both maps were mostly consistent but local defects were better visualized in OCT-derived thickness maps.

  9. Risk factors for retinal breaks in patients with symptom of floaters.

    Science.gov (United States)

    Singalavanija, Apichart; Amornrattanapan, Chutiwan; Nitiruangjarus, Kanjanee; Tongsai, Sasima

    2010-06-01

    To identify the risk factors of retinal breaks in patients with the symptom of floaters, and to determine the association between those risk factors and retinal breaks. A retrospective analytic study of 184 patients (55 males and 129 females) that included 220 eyes was conducted. Patient information such as age, symptoms (multiple floaters, flashing), duration of symptom, refractive error, history of cataract surgery, family history of retinal detachment, and complete eye examination were recorded. The patients were divided into two groups, the first group (control group) had symptoms of floaters and no retinal breaks, the second group (retinal breaks group) had symptoms of floaters with retinal breaks. Chi-square test, and the multiple logistic regression were used for statistical analysis. Two hundred twenty eyes, 175 eyes of the control group and 45 eyes of the retinal breaks group were examined and included in this study. The multiple logistic regression analysis revealed that patients with multiple floaters, and floaters and flashing increased the risk of retinal breaks to 5.8 and 4.3 times, respectively, when compared to patients with single floater or floaters alone. Lattice degeneration increased the risk of retinal breaks to 5.9 times when compared to eyes that did not have lattice degeneration. Multiple floaters, flashing and lattice degeneration are risk factors of retinal breaks in patients with symptoms of floaters. Therefore, it is important for the ophthalmologists to be aware of these risk factors and the patients at risk should have follow-up examinations.

  10. Influence of Clinical Factors and Magnification Correction on Normal Thickness Profiles of Macular Retinal Layers Using Optical Coherence Tomography

    Science.gov (United States)

    Higashide, Tomomi; Ohkubo, Shinji; Hangai, Masanori; Ito, Yasuki; Shimada, Noriaki; Ohno-Matsui, Kyoko; Terasaki, Hiroko; Sugiyama, Kazuhisa; Chew, Paul; Li, Kenneth K. W.; Yoshimura, Nagahisa

    2016-01-01

    Purpose To identify the factors which significantly contribute to the thickness variabilities in macular retinal layers measured by optical coherence tomography with or without magnification correction of analytical areas in normal subjects. Methods The thickness of retinal layers {retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCLIPL), RNFL plus GCLIPL (ganglion cell complex, GCC), total retina, total retina minus GCC (outer retina)} were measured by macular scans (RS-3000, NIDEK) in 202 eyes of 202 normal Asian subjects aged 20 to 60 years. The analytical areas were defined by three concentric circles (1-, 3- and 6-mm nominal diameters) with or without magnification correction. For each layer thickness, a semipartial correlation (sr) was calculated for explanatory variables including age, gender, axial length, corneal curvature, and signal strength index. Results Outer retinal thickness was significantly thinner in females than in males (sr2, 0.07 to 0.13) regardless of analytical areas or magnification correction. Without magnification correction, axial length had a significant positive sr with RNFL (sr2, 0.12 to 0.33) and a negative sr with GCLIPL (sr2, 0.22 to 0.31), GCC (sr2, 0.03 to 0.17), total retina (sr2, 0.07 to 0.17) and outer retina (sr2, 0.16 to 0.29) in multiple analytical areas. The significant sr in RNFL, GCLIPL and GCC became mostly insignificant following magnification correction. Conclusions The strong correlation between the thickness of inner retinal layers and axial length appeared to result from magnification effects. Outer retinal thickness may differ by gender and axial length independently of magnification correction. PMID:26814541

  11. Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung-A [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of); Shim, Sang Hee [School of Biotechnology, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Ahn, Hong Ryul [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of); Jung, Sang Hoon, E-mail: shjung507@gmail.com [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of)

    2013-06-01

    The mechanism underlying glaucoma remains controversial, but apoptosis caused by increased levels of reactive oxygen species (ROS) is thought to play a role in its pathogenesis. We investigated the effects of compounds isolated from Psoralea corylifolia on oxidative stress-induced cell death in vitro and in vivo. Transformed retinal ganglion cells (RGC-5) were treated with L-buthione-(S,R)-sulfoximine (BSO) and glutamate in the presence or with pre-treatment with compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhibited the oxidative stress-induced decrease of mitochondrial membrane potential (MMP, ΔΨm). Furthermore, while intracellular Ca{sup 2+} was high in RGC-5 cells after exposure to oxidative stress, bakuchiol reduced these levels. In an in vivo study, in which rat retinal damage was induced by intravitreal injection of N-methyl-D-aspartate (NMDA), bakuchiol markedly reduced translocation of AIF and release of cytochrome c, and inhibited up-regulation of cleaved caspase-3, cleaved caspase-9, and cleaved PARP. The survival rate of retinal ganglion cells (RGCs) 7 days after optic nerve crush (ONC) in mice was significantly decreased; however, bakuchiol attenuated the loss of RGCs. Moreover, bakuchiol attenuated ONC-induced up-regulation of apoptotic proteins, including cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Bakuchiol also significantly inhibited translocation of mitochondrial AIF into the nuclear fraction and release of mitochondrial cytochrome c into the cytosol. These results demonstrate that bakuchiol isolated from P. corylifolia has protective effects against oxidative stress-induced retinal damage, and may be considered as an agent for treating or preventing retinal degeneration. - Highlights: • Psoralea corylifolia have neuroprotective effects in vitro and in vivo. • Bakuchiol attenuated the increase of apoptotic proteins induced by oxidative

  12. Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage

    International Nuclear Information System (INIS)

    Kim, Kyung-A; Shim, Sang Hee; Ahn, Hong Ryul; Jung, Sang Hoon

    2013-01-01

    The mechanism underlying glaucoma remains controversial, but apoptosis caused by increased levels of reactive oxygen species (ROS) is thought to play a role in its pathogenesis. We investigated the effects of compounds isolated from Psoralea corylifolia on oxidative stress-induced cell death in vitro and in vivo. Transformed retinal ganglion cells (RGC-5) were treated with L-buthione-(S,R)-sulfoximine (BSO) and glutamate in the presence or with pre-treatment with compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhibited the oxidative stress-induced decrease of mitochondrial membrane potential (MMP, ΔΨm). Furthermore, while intracellular Ca 2+ was high in RGC-5 cells after exposure to oxidative stress, bakuchiol reduced these levels. In an in vivo study, in which rat retinal damage was induced by intravitreal injection of N-methyl-D-aspartate (NMDA), bakuchiol markedly reduced translocation of AIF and release of cytochrome c, and inhibited up-regulation of cleaved caspase-3, cleaved caspase-9, and cleaved PARP. The survival rate of retinal ganglion cells (RGCs) 7 days after optic nerve crush (ONC) in mice was significantly decreased; however, bakuchiol attenuated the loss of RGCs. Moreover, bakuchiol attenuated ONC-induced up-regulation of apoptotic proteins, including cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Bakuchiol also significantly inhibited translocation of mitochondrial AIF into the nuclear fraction and release of mitochondrial cytochrome c into the cytosol. These results demonstrate that bakuchiol isolated from P. corylifolia has protective effects against oxidative stress-induced retinal damage, and may be considered as an agent for treating or preventing retinal degeneration. - Highlights: • Psoralea corylifolia have neuroprotective effects in vitro and in vivo. • Bakuchiol attenuated the increase of apoptotic proteins induced by oxidative

  13. Adenosine A2A Receptor Up-Regulates Retinal Wave Frequency via Starburst Amacrine Cells in the Developing Rat Retina

    Science.gov (United States)

    Huang, Pin-Chien; Hsiao, Yu-Tien; Kao, Shao-Yen; Chen, Ching-Feng; Chen, Yu-Chieh; Chiang, Chung-Wei; Lee, Chien-fei; Lu, Juu-Chin; Chern, Yijuang; Wang, Chih-Tien

    2014-01-01

    Background Developing retinas display retinal waves, the patterned spontaneous activity essential for circuit refinement. During the first postnatal week in rodents, retinal waves are mediated by synaptic transmission between starburst amacrine cells (SACs) and retinal ganglion cells (RGCs). The neuromodulator adenosine is essential for the generation of retinal waves. However, the cellular basis underlying adenosine's regulation of retinal waves remains elusive. Here, we investigated whether and how the adenosine A2A receptor (A2AR) regulates retinal waves and whether A2AR regulation of retinal waves acts via presynaptic SACs. Methodology/Principal Findings We showed that A2AR was expressed in the inner plexiform layer and ganglion cell layer of the developing rat retina. Knockdown of A2AR decreased the frequency of spontaneous Ca2+ transients, suggesting that endogenous A2AR may up-regulate wave frequency. To investigate whether A2AR acts via presynaptic SACs, we targeted gene expression to SACs by the metabotropic glutamate receptor type II promoter. Ca2+ transient frequency was increased by expressing wild-type A2AR (A2AR-WT) in SACs, suggesting that A2AR may up-regulate retinal waves via presynaptic SACs. Subsequent patch-clamp recordings on RGCs revealed that presynaptic A2AR-WT increased the frequency of wave-associated postsynaptic currents (PSCs) or depolarizations compared to the control, without changing the RGC's excitability, membrane potentials, or PSC charge. These findings suggest that presynaptic A2AR may not affect the membrane properties of postsynaptic RGCs. In contrast, by expressing the C-terminal truncated A2AR mutant (A2AR-ΔC) in SACs, the wave frequency was reduced compared to the A2AR-WT, but was similar to the control, suggesting that the full-length A2AR in SACs is required for A2AR up-regulation of retinal waves. Conclusions/Significance A2AR up-regulates the frequency of retinal waves via presynaptic SACs, requiring its full

  14. Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina.

    Science.gov (United States)

    Huang, Pin-Chien; Hsiao, Yu-Tien; Kao, Shao-Yen; Chen, Ching-Feng; Chen, Yu-Chieh; Chiang, Chung-Wei; Lee, Chien-Fei; Lu, Juu-Chin; Chern, Yijuang; Wang, Chih-Tien

    2014-01-01

    Developing retinas display retinal waves, the patterned spontaneous activity essential for circuit refinement. During the first postnatal week in rodents, retinal waves are mediated by synaptic transmission between starburst amacrine cells (SACs) and retinal ganglion cells (RGCs). The neuromodulator adenosine is essential for the generation of retinal waves. However, the cellular basis underlying adenosine's regulation of retinal waves remains elusive. Here, we investigated whether and how the adenosine A(2A) receptor (A(2A)R) regulates retinal waves and whether A(2A)R regulation of retinal waves acts via presynaptic SACs. We showed that A(2A)R was expressed in the inner plexiform layer and ganglion cell layer of the developing rat retina. Knockdown of A(2A)R decreased the frequency of spontaneous Ca²⁺ transients, suggesting that endogenous A(2A)R may up-regulate wave frequency. To investigate whether A(2A)R acts via presynaptic SACs, we targeted gene expression to SACs by the metabotropic glutamate receptor type II promoter. Ca²⁺ transient frequency was increased by expressing wild-type A(2A)R (A2AR-WT) in SACs, suggesting that A(2A)R may up-regulate retinal waves via presynaptic SACs. Subsequent patch-clamp recordings on RGCs revealed that presynaptic A(2A)R-WT increased the frequency of wave-associated postsynaptic currents (PSCs) or depolarizations compared to the control, without changing the RGC's excitability, membrane potentials, or PSC charge. These findings suggest that presynaptic A(2A)R may not affect the membrane properties of postsynaptic RGCs. In contrast, by expressing the C-terminal truncated A(2A)R mutant (A(2A)R-ΔC) in SACs, the wave frequency was reduced compared to the A(2A)R-WT, but was similar to the control, suggesting that the full-length A(2A)R in SACs is required for A(2A)R up-regulation of retinal waves. A(2A)R up-regulates the frequency of retinal waves via presynaptic SACs, requiring its full-length protein structure. Thus, by

  15. Adenosine A(2A receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina.

    Directory of Open Access Journals (Sweden)

    Pin-Chien Huang

    Full Text Available BACKGROUND: Developing retinas display retinal waves, the patterned spontaneous activity essential for circuit refinement. During the first postnatal week in rodents, retinal waves are mediated by synaptic transmission between starburst amacrine cells (SACs and retinal ganglion cells (RGCs. The neuromodulator adenosine is essential for the generation of retinal waves. However, the cellular basis underlying adenosine's regulation of retinal waves remains elusive. Here, we investigated whether and how the adenosine A(2A receptor (A(2AR regulates retinal waves and whether A(2AR regulation of retinal waves acts via presynaptic SACs. METHODOLOGY/PRINCIPAL FINDINGS: We showed that A(2AR was expressed in the inner plexiform layer and ganglion cell layer of the developing rat retina. Knockdown of A(2AR decreased the frequency of spontaneous Ca²⁺ transients, suggesting that endogenous A(2AR may up-regulate wave frequency. To investigate whether A(2AR acts via presynaptic SACs, we targeted gene expression to SACs by the metabotropic glutamate receptor type II promoter. Ca²⁺ transient frequency was increased by expressing wild-type A(2AR (A2AR-WT in SACs, suggesting that A(2AR may up-regulate retinal waves via presynaptic SACs. Subsequent patch-clamp recordings on RGCs revealed that presynaptic A(2AR-WT increased the frequency of wave-associated postsynaptic currents (PSCs or depolarizations compared to the control, without changing the RGC's excitability, membrane potentials, or PSC charge. These findings suggest that presynaptic A(2AR may not affect the membrane properties of postsynaptic RGCs. In contrast, by expressing the C-terminal truncated A(2AR mutant (A(2AR-ΔC in SACs, the wave frequency was reduced compared to the A(2AR-WT, but was similar to the control, suggesting that the full-length A(2AR in SACs is required for A(2AR up-regulation of retinal waves. CONCLUSIONS/SIGNIFICANCE: A(2AR up-regulates the frequency of retinal waves via

  16. An alternative pathway for signal flow from rod photoreceptors to ganglion cells in mammalian retina.

    OpenAIRE

    DeVries, S H; Baylor, D A

    1995-01-01

    Rod signals in the mammalian retina are thought to reach ganglion cells over the circuit rod-->rod depolarizing bipolar cell-->AII amacrine cell-->cone bipolar cells-->ganglion cells. A possible alternative pathway involves gap junctions linking the rods and cones, the circuit being rod-->cone-->cone bipolar cells-->ganglion cells. It is not clear whether this second pathway indeed relays rod signals to ganglion cells. We studied signal flow in the isolated rabbit retina with a multielectrode...

  17. 30{mu}m spacing 519-electrode arrays for in vitro retinal studies

    Energy Technology Data Exchange (ETDEWEB)

    Gunning, D. [Department of Physics and Astronomy, University of Glasgow, G12 8QQ, Scotland (United Kingdom)]. E-mail: d.gunning@physics.gla.ac.uk; Adams, C. [Department of Physics and Astronomy, University of Glasgow, G12 8QQ, Scotland (United Kingdom); Cunningham, W. [Department of Physics and Astronomy, University of Glasgow, G12 8QQ, Scotland (United Kingdom); Mathieson, K. [Department of Physics and Astronomy, University of Glasgow, G12 8QQ, Scotland (United Kingdom); O' Shea, V. [Department of Physics and Astronomy, University of Glasgow, G12 8QQ, Scotland (United Kingdom); Smith, K.M. [Department of Physics and Astronomy, University of Glasgow, G12 8QQ, Scotland (United Kingdom); Chichilnisky, E.J. [The Salk Institute for Biological Studies, La Jolla, CA 92037-1099 (United States); Litke, A.M. [SCIPP, University of California Santa Cruz, Santa Cruz, CA 95064 (United States); Rahman, M. [Department of Physics and Astronomy, University of Glasgow, G12 8QQ, Scotland (United Kingdom)

    2005-07-01

    To understand how biological neural networks, such as the retina, process information, transparent microelectrode arrays have been made using the semiconductor indium tin oxide (ITO). These arrays have been used for in vitro biological experiments where it is possible to record simultaneously the action potentials from hundreds of retinal ganglion cells. To combat inefficient detection of a particular class of retinal output neuron, an array with 30{mu}m spaced 519-electrodes has been developed. These arrays are characterised electrically before being employed in biological experiments. With a view to future higher density arrays, impedance and capacitance measurements were made over varying width, length and separation of ITO wires. These tests led to an equivalent circuit model representing electrode array characteristics. The results suggest array sizes of 2000 electrodes and beyond should be feasible.

  18. Inherited Retinal Degenerative Disease Registry

    Science.gov (United States)

    2017-09-13

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  19. Blocking retinal chloride co-transporters KCC2 and NKCC: impact on direction selective ON and OFF responses in the rat's nucleus of the optic tract.

    Directory of Open Access Journals (Sweden)

    Katharina Spoida

    Full Text Available In the present study we investigated in vivo the effects of pharmacological manipulation of retinal processing on the response properties of direction selective retinal slip cells in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN, the key visuomotor interface in the pathway underlying the optokinetic reflex. Employing a moving visual stimulus consisting of either a large dark or light edge we could differentiate direction selective ON and OFF responses in retinal slip cells. To disclose the origin of the retinal slip cells' unexpected OFF response we selectively blocked the retinal ON channels and inactivated the visual cortex by cooling. Cortical cooling had no effect on the direction selectivity of the ON or the OFF response in NOT-DTN retinal slip cells. Blockade of the retinal ON channel with APB led to a loss of the ON and, to a lesser degree, of the OFF response and a reduction in direction selectivity. Subsequent blocking of GABA receptors in the retina with picrotoxin unmasked a vigorous albeit direction unselective OFF response in the NOT-DTN. Disturbing the retinal chloride homeostasis by intraocular injections of bumetanide or furosemide led to a loss of direction selectivity in both the NOT-DTN's ON and the OFF response due to a reduced response in the neuron's preferred direction under bumetanide as well as under furosemide and a slightly increased response in the null direction under bumetanide. Our results indicate that the direction specificity of retinal slip cells in the NOT-DTN of the rat strongly depends on direction selective retinal input which depends on intraretinal chloride homeostasis. On top of the well established input from ON center direction selective ganglion cells we could demonstrate an equally effective input from the retinal OFF system to the NOT-DTN.

  20. File list: Oth.Neu.05.AllAg.Superior_Cervical_Ganglion [Chip-atlas[Archive

    Lifescience Database Archive (English)

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