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  1. Intrinsically photosensitive retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    Gary; E.PICKARD; Patricia; J.SOLLARS

    2010-01-01

    A new mammalian photoreceptor was recently discovered to reside in the ganglion cell layer of the inner retina.These intrinsically photosensitive retinal ganglion cells(ipRGCs) express a photopigment,melanopsin,that confers upon them the ability to respond to light in the absence of all rod and cone photoreceptor input.Although relatively few in number,ipRGCs extend their dendrites across large expanses of the retina making them ideally suited to function as irradiance detectors to assess changes in ambient light levels.Phototransduction in ipRGCs appears to be mediated by transient receptor potential channels more closely resembling the phototransduction cascade of invertebrate rather than vertebrate photoreceptors.ipRGCs convey irradiance information centrally via the optic nerve to influence several functions.ipRGCs are the primary retinal input to the hypothalamic suprachiasmatic nucleus(SCN),a circadian oscillator and biological clock,and this input entrains the SCN to the day/night cycle.ipRGCs contribute irradiance signals that regulate pupil size and they also provide signals that interface with the autonomic nervous system to regulate rhythmic gene activity in major organs of the body.ipRGCs also provide excitatory drive to dopaminergic amacrine cells in the retina,providing a novel basis for the restructuring of retinal circuits by light.Here we review the ground-breaking discoveries,current progress and directions for future investigation.

  2. Melanopsin expressing human retinal ganglion cells

    DEFF Research Database (Denmark)

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

    2017-01-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex and sleep/wake cycles. The different functions seem...

  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. Genetic Networks in Mouse Retinal Ganglion Cells

    Directory of Open Access Journals (Sweden)

    Felix L Struebing

    2016-09-01

    Full Text Available Retinal ganglion cells (RGCs are the output neuron of the eye, transmitting visual information from the retina through the optic nerve to the brain. The importance of RGCs for vision is demonstrated in blinding diseases where RGCs are lost, such as in glaucoma or after optic nerve injury. In the present study, we hypothesize that normal RGC function is transcriptionally regulated. To test our hypothesis, we examine large retinal expression microarray datasets from recombinant inbred mouse strains in GeneNetwork and define transcriptional networks of RGCs and their subtypes. Two major and functionally distinct transcriptional networks centering around Thy1 and Tubb3 (Class III beta-tubulin were identified. Each network is independently regulated and modulated by unique genomic loci. Meta-analysis of publically available data confirms that RGC subtypes are differentially susceptible to death, with alpha-RGCs and intrinsically photosensitive RGCs (ipRGCs being less sensitive to cell death than other RGC subtypes in a mouse model of glaucoma.

  6. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    OpenAIRE

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

    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 inc...

  7. 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

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Retinal ganglion cell adaptation to small luminance fluctuations.

    Science.gov (United States)

    Freeman, Daniel K; Graña, Gilberto; Passaglia, Christopher L

    2010-08-01

    To accommodate the wide input range over which the visual system operates within the narrow output range of spiking neurons, the retina adjusts its sensitivity to the mean light level so that retinal ganglion cells can faithfully signal contrast, or relative deviations from the mean luminance. Given the large operating range of the visual system, the majority of work on luminance adaptation has involved logarithmic changes in light level. We report that luminance gain controls are recruited for remarkably small fluctuations in luminance as well. Using spike recordings from the rat optic tract, we show that ganglion cell responses to a brief flash of light are modulated in amplitude by local background fluctuations as little as 15% contrast. The time scale of the gain control is rapid (retinal locus of adaptation precedes the ganglion cell spike generator because response gain changes of on cells were uncorrelated with firing rate. The mechanism seems to reside within the inner retinal network and not in the photoreceptors, because the adaptation profiles of on and off cells differed markedly. The response gain changes follow Weber's law, suggesting that network mechanisms of luminance adaptation described in previous work modulates retinal ganglion cell sensitivity, not just when we move between different lighting environments, but also as our eyes scan a visual scene. Finally, we show that response amplitude is uniformly reduced for flashes on a modulated background that has spatial contrast, indicating that another gain control that integrates luminance signals nonlinearly over space operates within the receptive field center of rat ganglion cells.

  11. The functional diversity of retinal ganglion cells in the mouse.

    Science.gov (United States)

    Baden, Tom; Berens, Philipp; Franke, Katrin; Román Rosón, Miroslav; Bethge, Matthias; Euler, Thomas

    2016-01-21

    In the vertebrate visual system, all output of the retina is carried by retinal ganglion cells. Each type encodes distinct visual features in parallel for transmission to the brain. How many such 'output channels' exist and what each encodes are areas of intense debate. In the mouse, anatomical estimates range from 15 to 20 channels, and only a handful are functionally understood. By combining two-photon calcium imaging to obtain dense retinal recordings and unsupervised clustering of the resulting sample of more than 11,000 cells, here we show that the mouse retina harbours substantially more than 30 functional output channels. These include all known and several new ganglion cell types, as verified by genetic and anatomical criteria. Therefore, information channels from the mouse eye to the mouse brain are considerably more diverse than shown thus far by anatomical studies, suggesting an encoding strategy resembling that used in state-of-the-art artificial vision systems.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  14. Inhibition of BDNF-AS Provides Neuroprotection for Retinal Ganglion Cells against Ischemic Injury

    OpenAIRE

    Xu, Lifang; Zhang, Ziyin; Xie, Tianhua; Zhang, Xiaoyang; Dai, Tu

    2016-01-01

    Background: Brain-derived neurotrophic factor (BDNF) protects retinal ganglion cells against ischemia in ocular degenerative diseases. We aimed to determine the effect of BDNF-AS on the ischemic injury of retinal ganglion cells. Methods: The levels of BDNF and BDNF-AS were measured in retinal ganglion cells subjected to oxygen and glucose deprivation. The lentiviral vectors were constructed to either overexpress or knock out BDNF-AS. The luciferase reporter gene assay was used to determine wh...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

    Neuropeptide Y (NPY) is expressed in mammalian retina but the location and potential modulatory effects of NPY receptor activation remain largely unknown. Retinal ganglion cell (RGC) death is a hallmark of several retinal degenerative diseases, particularly glaucoma. Using purified RGCs and ex vivo...... actions detected in retinal explants can be translated into animal models of retinal degenerative diseases....

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    Directory of Open Access Journals (Sweden)

    Nicolas Froger

    Full Text Available 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.

  19. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    Science.gov (United States)

    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.

  20. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    Science.gov (United States)

    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

  1. Retrograde degeneration of retinal ganglion cells in homonymous hemianopsia

    Directory of Open Access Journals (Sweden)

    Herro AM

    2015-06-01

    Full Text Available Angela M Herro, Byron L Lam Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, USA Background: The aim of this study was to demonstrate the relationship between topographic reduction in macular ganglion cell complex (GCC thickness as detected with spectral-domain optical coherence tomography and visual field defects caused by ischemic occipital cortical injury.Methods: This study was a retrospective review of all patients who presented to our eye institution between January 2012 and July 2014 with visual field defects secondary to ischemic cortical injury. The visual field defect pattern and mean deviation were analyzed. Retinal nerve fiber layer (RNFL and macular GCC were both assessed with spectral-domain optical coherence tomography. Patients with any ocular pathology that could affect these measurements were excluded. The topographic relationship of visual field defect to reduction in GCC was specifically analyzed. Results: Nine patients met the inclusion criteria. Their average age was 65 (57–73 years; eight were men and six had right hemianopsias. The laterality of the visual field defect was used to assign an affected and unaffected side of analysis for RNFL and GCC layer thickness. A right hemianopsia meant that the nasal fibers of the right eye and temporal fibers of the left eye were assigned as the “affected side”, and the temporal fibers of the right eye and nasal fibers of the left eye were assigned as “unaffected”. There was no statistically significant difference between affected and unaffected RNFL. However, there was a significant difference in GCC layer reduction between the affected and unaffected sides (P=0.029.Conclusion: There is evidence of retrograde trans-synaptic retinal ganglion cell loss in patients with homonymous hemianopsias from cortical visual impairment. This relationship is reflected in thinning of the GCC and maintains the topographic

  2. Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells.

    Science.gov (United States)

    Middleton, T P; Protti, D A

    2011-09-01

    The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14-P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.

  3. Melanopsin retinal ganglion cell loss in Alzheimer disease

    Science.gov (United States)

    Ross‐Cisneros, Fred N.; Koronyo, Yosef; Hannibal, Jens; Gallassi, Roberto; Cantalupo, Gaetano; Sambati, Luisa; Pan, Billy X.; Tozer, Kevin R.; Barboni, Piero; Provini, Federica; Avanzini, Pietro; Carbonelli, Michele; Pelosi, Annalisa; Chui, Helena; Liguori, Rocco; Baruzzi, Agostino; Koronyo‐Hamaoui, Maya; Sadun, Alfredo A.; Carelli, Valerio

    2015-01-01

    Objective Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction. Methods We assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls. Results We demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs. Interpretation We show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109 PMID:26505992

  4. Specific inhibition of TRPV4 enhances retinal ganglion cell survival in adult porcine retinal explants.

    Science.gov (United States)

    Taylor, Linnéa; Arnér, Karin; Ghosh, Fredrik

    2017-01-01

    Signaling through the polymodal cation channel Transient Receptor Potential Vanilloid 4 (TRPV4) has been implicated in retinal neuronal degeneration. To further outline the involvement of this channel in this process, we here explore modulation of Transient Receptor Potential Vanilloid 4 (TRPV4) activity on neuronal health and glial activation in an in vitro model of retinal degeneration. For this purpose, adult porcine retinal explants were cultured using a previously established standard protocol for up to 5 days with specific TRPV4 agonist GSK1016790A (GSK), or specific antagonist RN-1734, or culture medium only. Glial and neuronal cell health were evaluated by a battery of immunohistochemical markers, as well as morphological staining. Specific inhibition of TRPV4 by RN-1734 significantly enhanced ganglion cell survival, improved the maintenance of the retinal laminar architecture, reduced apoptotic cell death and attenuated the gliotic response as well as preserved the expression of TRPV4 in the plexiform layers and ganglion cells. In contrast, culture controls, as well as specimens treated with GSK, displayed rapid remodeling and neurodegeneration as well as a downregulation of TRPV4 and the Müller cell homeostatic mediator glutamine synthetase. Our results indicate that TRPV4 signaling is an important contributor to the retinal degeneration in this model, affecting neuronal cell health and glial homeostasis. The finding that pharmacological inhibition of the receptor significantly attenuates neuronal degeneration and gliosis in vitro, suggests that TRPV4 signaling may be an interesting pharmaceutical target to explore for treatment of retinal degenerative disease.

  5. Contrast Adaptation Decreases Complexity in Retinal Ganglion Cell Spike Train

    Institute of Scientific and Technical Information of China (English)

    WANG Guang-Li; HUANG Shi-Yong; ZHANG Ying-Ying; LIANG Pei-Ji

    2007-01-01

    @@ The difference in temporal structures of retinal ganglion cell spike trains between spontaneous activity and firing activity after contrast adaptation is investigated. The Lempel-Ziv complexity analysis reveals that the complexity of the neural spike train decreases after contrast adaptation. This implies that the behaviour of the neuron becomes ordered, which may carry relevant information about the external stimulus. Thus, during the neuron activity after contrast adaptation, external information could be encoded in forms of some certain patterns in the temporal structure of spike train that is significantly different, compared to that of the spike train during spontaneous activity, although the firing rates in spontaneous activity and firing activity after contrast adaptation are sometime similar.

  6. Retinal ganglion cell density of the black rhinoceros (Diceros bicornis): calculating visual resolution.

    Science.gov (United States)

    Pettigrew, John D; Manger, Paul R

    2008-01-01

    A single right retina from a black rhinoceros was whole mounted, stained and analyzed to determine the visual resolution of the rhinoceros, an animal with reputedly poor eyesight. A range of small (15-microm diameter) to large (100-microm diameter) ganglion cell types was seen across the retina. We observed two regions of high density of retinal ganglion cells at either end of a long, but thin, horizontal streak. The temporal specialization, which receives light from the anterior visual field, exhibited a ganglion cell density of approximately 2000/mm2, while the nasal specialization exhibited a density of approximately 1500/mm2. The retina exhibited a ganglion cell density bias toward the upper half, especially so, the upper temporal quadrant, indicating that the rhinoceros would be processing visual information from the visual field below the anterior horizon for the most part. Our calculations indicate that the rhinoceros has a visual resolution of 6 cycles/degree. While this resolution is one-tenth that of humans (60 cycles/deg) and less than that of the domestic cat (9 cycles/deg), it is comparable to that of the rabbit (6 cycles/deg), and exceeds that seen in a variety of other mammals including seals, dolphins, microbats, and rats. Thus, the reputation of the rhinoceros as a myopic, weakly visual animal is not supported by our observations of the retina. We calculate that the black rhinoceros could readily distinguish a 30 cm wide human at a distance of around 200 m given the appropriate visual background.

  7. Enriched retinal ganglion cells derived from human embryonic stem cells

    Science.gov (United States)

    Gill, Katherine P.; Hung, Sandy S. C.; Sharov, Alexei; Lo, Camden Y.; Needham, Karina; Lidgerwood, Grace E.; Jackson, Stacey; Crombie, Duncan E.; Nayagam, Bryony A.; Cook, Anthony L.; Hewitt, Alex W.; Pébay, Alice; Wong, Raymond C. B.

    2016-01-01

    Optic neuropathies are characterised by a loss of retinal ganglion cells (RGCs) that lead to vision impairment. Development of cell therapy requires a better understanding of the signals that direct stem cells into RGCs. Human embryonic stem cells (hESCs) represent an unlimited cellular source for generation of human RGCs in vitro. In this study, we present a 45-day protocol that utilises magnetic activated cell sorting to generate enriched population of RGCs via stepwise retinal differentiation using hESCs. We performed an extensive characterization of these stem cell-derived RGCs by examining the gene and protein expressions of a panel of neural/RGC markers. Furthermore, whole transcriptome analysis demonstrated similarity of the hESC-derived RGCs to human adult RGCs. The enriched hESC-RGCs possess long axons, functional electrophysiological profiles and axonal transport of mitochondria, suggestive of maturity. In summary, this RGC differentiation protocol can generate an enriched population of functional RGCs from hESCs, allowing future studies on disease modeling of optic neuropathies and development of cell therapies. PMID:27506453

  8. A filter based encoding model for mouse retinal ganglion cells.

    Science.gov (United States)

    Zhong, Q; Roychowdhury, V; Boykin, P; Jacobs, A; Nirenberg, S

    2005-01-01

    We adopt a system theoretic approach and explore the model of retinal ganglion cells as linear filters followed by a maximum-likelihood Bayesian predictor. We evaluate the model by using cross-validation, i.e., first the model parameters are estimated using a training set, and then the prediction error is computed (by comparing the stochastic rate predicted by the model with the rate code of the response) for a test set. As in system identification theory, we present spatially uniform stimuli to the retina, whose temporal intensity is drawn independently from a Gaussian distribution, and we simultaneously record the spike trains from multiple neurons. The optimal linear filter for each cell is obtained by maximizing the mutual information between the filtered stimulus values and the output of the cell (as measured in terms of a stochastic rate code). Our results show that the model presented in this paper performs well on the test set, and it outperforms the identity Bayesian model and the traditional linear model. Moreover, in order to reduce the number of optimal filters needed for prediction, we cluster the cells based on the filters' shapes, and use the cluster consensus filters to predict the firing rates of all neurons in the same class. We obtain almost the same performance with these cluster filters. These results provide hope that filter-based retinal prosthetics might be an effective and feasible idea.

  9. Evaluation of ultraviolet light toxicity on cultured retinal pigment epithelial and retinal ganglion cells

    Directory of Open Access Journals (Sweden)

    Sankarathi Balaiya

    2010-01-01

    Full Text Available Sankarathi Balaiya, Ravi K Murthy, Vikram S Brar, Kakarla V ChalamDepartment of Ophthalmology, University of Florida College of Medicine, Jacksonville, FL, USAPurpose: Our study is aimed at evaluating the role of UVB light in inducing cytotoxicity in an in vitro model.Methods: RGC-5 and ARPE-19 cells were exposed to different time periods of UVB light: 0, 15, 30, and 45 min. They were subsequently examined for changes in cell morphology, cell viability (neutral red uptake assay, generation of reactive oxygen species (ROS, expression of bax, bcl-2 and cytochome C by reverse transcriptase polymerase chain reaction and western blot, respectively.Results: Dose-dependent reduction in cell viability to UVB light was demonstrated with parallel increase in ROS. Increased duration of exposure (>15 minutes, was associated with increased expression of bax and cytochrome C, and absence of bcl-2 expression.Conclusion: UVB light exposure results in cell cytotoxicity. The concomitant generation of ROS and expression of apoptotic markers suggests the role of oxidative stress in UVB-mediated apoptosis in an in vitro model of retinal ganglion and pigment epithelial cells.Keywords: ultraviolet light, retinal pigment epithelium, retinal ganglion cell, reactive oxygen species, cytochrome C

  10. Caspase-dependent retinal ganglion cell apoptosis in the rat model of acute diabetes

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Neural apoptosis is generally believed to be mediated by two distinct pathways, caspase-dependant and caspase-independent pathways. This study investigated the apoptotic pathways involved in retinal ganglion ceils in acute diabetes in rats. Methods Diabetes was induced in male Wistar rats by a peritoneal injection of streptozotocin (STZ). Expression and localization of caspase-3 and apoptosis-inducing factor (AIF) proteins in the retina of diabetic rats was examined by Western blotting and immunohistochemistry analyses. Terminal transferase dUTP nick end labeling (TUNEL) assay and immunofluorescent staining specific for caspase-3 and AIF were applied to analyze for apoptosis of retinal ganglion cells. In addition, a caspase-3 inhibitor DEVD-CHO was injected intravitreally to further determine the apoptotic pathways of retinal ganglion cells triggered in acute diabetes. Results Two weeks after induction of diabetes, a significant increase in caspase-3 protein expression and localization occurred in the nerve fiber layer, ganglion cell layer, and inner plexiform layer of the retina. Four weeks after the onset of diabetes, the increase in caspase-3 expression was profound eight weeks postinduction of diabetes (P<0.05). Meanwhile, no AIF protein expression was detected in this study. In addition, intravitreal administration of the caspase-3 inhibitor DEVD-CHO reduced apoptosis of retinal ganglion cells by its direct inhibitory action on caspase-3. Conclusion Caspase-dependent apoptotic pathways may be the main stimulant of STZ-induced retinal ganglion cell apoptosis in acute diabetes.

  11. Retinal ganglion cells of high cytochrome oxidase activity in the rat

    Institute of Scientific and Technical Information of China (English)

    JENLS; CHAURMW

    1990-01-01

    Retinal ganglion cells in the rat were studied using the heavy metal intensified cytochrome oxidase and horseradish peroxidase histochemical methods.The results show that a population of large retinal ganglion cells was consistently observed with the cytochrome oxidase staining method in retinas of normal rats or rats which received unilateral thalamotomy at birth.These cytochrome oxidase rich ganglion cells appeared to have large somata,3-6 primary dendrites and extensive dendritic arbors,and are comparable to ganglion cells labeled by the wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP).However,the morphological details of some of the cells revealed by the cytochrome oxidase staining method are frequently better than those shown by the HRP histochemical method.These results suggest that the mitochondrial enzyme cytochrome oxidase can be used as a simple but reliable marker for identifying and studying a population of retinal genglion cells with high metabolic rate in the rat.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Developmental patterning of glutamatergic synapses onto retinal ganglion cells

    Directory of Open Access Journals (Sweden)

    Schubert Timm

    2008-03-01

    Full Text Available Abstract Background Neurons receive excitatory synaptic inputs that are distributed across their dendritic arbors at densities and with spatial patterns that influence their output. How specific synaptic distributions are attained during development is not well understood. The distribution of glutamatergic inputs across the dendritic arbors of mammalian retinal ganglion cells (RGCs has long been correlated to the spatial receptive field profiles of these neurons. Thus, determining how glutamatergic inputs are patterned onto RGC dendritic arbors during development could provide insight into the cellular mechanisms that shape their functional receptive fields. Results We transfected developing and mature mouse RGCs with plasmids encoding fluorescent proteins that label their dendrites and glutamatergic postsynaptic sites. We found that as dendritic density (dendritic length per unit area of dendritic field decreases with maturation, the density of synapses along the dendrites increases. These changes appear coordinated such that RGCs attain the mature average density of postsynaptic sites per unit area (areal density by the time synaptic function emerges. Furthermore, stereotypic centro-peripheral gradients in the areal density of synapses across the arbor of RGCs are established at an early developmental stage. Conclusion The spatial pattern of glutamatergic inputs onto RGCs arises early in synaptogenesis despite ensuing reorganization of dendritic structure. We raise the possibility that these early patterns of synaptic distributions may arise from constraints placed on the number of contacts presynaptic neurons are able to make with the RGCs.

  14. Selective degeneration of the parvocellular-projecting retinal ganglion cells in a New World monkey, Saimiri sciureus.

    Science.gov (United States)

    Lynch, J J; Eskin, T A; Merigan, W H

    1989-10-16

    Selective degeneration of retinal ganglion cells projecting to parvocellular layers of the dorsal lateral geniculate nucleus (LGN) was observed in squirrel monkeys (Saimiri sciureus) exposed to a range of doses of acrylamide monomer. Similar acrylamide-induced neuronal loss has previously been reported in parvocellular-projecting ganglion cells of macaques, but no such selective degeneration has been found in acrylamide-dosed rats, squirrels, rabbits or cats. The extent of ganglion cell loss observed in the present study suggests that in the squirrel monkey, as in the macaque, a majority of ganglion cells project to parvocellular layers of the LGN. The locus of optic tract degeneration suggests that the squirrel monkey parvocellular pathway passes in dorsolateral optic tract, as does that of the macaque. Patterns of decreases in cytochrome oxidase activity confirm that, in both of these primates, geniculocortical pathways driven by these vulnerable neurons project to cortical layers 4A and 4C beta. These results suggest close parallels in the neuroanatomical projections and toxic vulnerability of the parvocellular-projecting pathway in New and Old World monkeys. They indicate that acrylamide intoxication can be used to selectively damage this pathway in order to study the functional roles of parallel visual pathways in both New and Old World monkeys.

  15. 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 retinal...... for the preservation of pupillary light reaction despite profound visual loss in patients with mitochondrial optic neuropathy, revealing the robustness of melanopsin retinal ganglion cells to a metabolic insult and opening the question of mechanisms that might protect these cells....... ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex...

  16. Effects of Lead on Temporal Response Properties of Retinal Ganglion Cells in Developing Rats

    Institute of Scientific and Technical Information of China (English)

    阮迪云; 汤立新; 赵晨; 郭宇静

    1994-01-01

    Neonatal rats have taken in lead, during the period from their parturition to their weaning, from the milk of dams fed with water containing 0.2% lead acetate solutions. The alterations in the temporal response properties of retinal ganglion cells in adult rats (90 days) following the lead exposure at their developing stage have been studied. The results of this investigation demonstrate that the lead exposure in neonatal rats causes decreases in the optimal temporal frequency, bandwidth at half amplitude, temporal resolution and response phase of the retinal ganglion cells in adult rats. Compared with the sustained cells, the transient cells have a much greater alteration in temporal response properties.

  17. Chicken retinal ganglion cells response characteristics: multi-channel electrode recording study

    Institute of Scientific and Technical Information of China (English)

    CHEN; Aihua; (陈爱华); ZHOU; Yi(周; 艺); GONG; Haiqing; (龚海庆); LIANG; Peiji; (梁培基)

    2003-01-01

    The first stage of visual processing occurs in the retina, the function of which is to process the raw information obtained from the outside world. In the present study, the electrical activities of a group of retinal ganglion cells were recorded from a small functioning piece of retina, using multi-electrode array (MEA), and the action potentials were detected by applying nonlinear algorithm. By analyzing the ensemble retinal ganglion output characteristics, it is revealed that both firing rates and correlated activity between adjacent neurons in the retina contribute to visual information encoding.

  18. Ganglion cell distribution and retinal resolution in the Florida manatee, Trichechus manatus latirostris.

    Science.gov (United States)

    Mass, Alla M; Ketten, Darlene R; Odell, Daniel K; Supin, Alexander Ya

    2012-01-01

    The topographic organization of retinal ganglion cells was examined in the Florida manatee (Trichechus manatus latirostris) to assess ganglion cell size and distribution and to estimate retinal resolution. The ganglion cell layer of the manatee's retina was comprised primarily of large neurons with broad intercellular spaces. Cell sizes varied from 10 to 60 μm in diameter (mean 24.3 μm). The retinal wholemounts from adult animals measured 446-501 mm(2) in area with total ganglion cell counts of 62,000-81,800 (mean 70,200). The cell density changed across the retina, with the maximum in the area below the optic disc and decreasing toward the retinal edges and in the immediate vicinity of the optic disc. The maximum cell density ranged from 235 to 337 cells per millimeter square in the adult retinae. Two wholemounts obtained from juvenile animals were 271 and 282 mm(2) in area with total cell numbers of 70,900 and 68,700, respectively (mean 69,800), that is, nearly equivalent to those of adults, but juvenile retinae consequently had maximum cell densities that were higher than those of adults: 478 and 491 cells per millimeter square. Calculations indicate a retinal resolution of ∼19' (1.6 cycles per degree) in both adult and juvenile retinae.

  19. Efficacy of electrical stimulation of retinal ganglion cells with temporal patterns resembling light-evoked spike trains.

    Science.gov (United States)

    Wong, Raymond C S; Garrett, David J; Grayden, David B; Ibbotson, Michael R; Cloherty, Shaun L

    2014-01-01

    People with degenerative retinal diseases such as retinitis pigmentosa lose most of their photoreceptors but retain a significant proportion (~30%) of their retinal ganglion cells (RGCs). Microelectronic retinal prostheses aim to bypass the lost photoreceptors and restore vision by directly stimulating the surviving RGCs. Here we investigate the extent to which electrical stimulation of RGCs can evoke neural spike trains with statistics resembling those of normal visually-evoked responses. Whole-cell patch clamp recordings were made from individual cat RGCs in vitro. We first recorded the responses of each cell to short sequences of visual stimulation. These responses were converted to trains of electrical stimulation that we then presented to the same cell via an epiretinal stimulating electrode. We then quantified the efficacy of the electrical stimuli and the latency of the evoked spikes. In all cases, spikes were evoked with sub-millisecond latency (0.55 ms, median, ON cells, n = 8; 0.75 ms, median, OFF cells, n = 6) and efficacy ranged from 0.4-1.0 (0.79, median, ON cells; 0.97, median, OFF cells). These data demonstrate that meaningful spike trains, resembling normal responses of RGCs to visual stimulation, can be reliably evoked by epiretinal prostheses.

  20. Neuroprotective Effect of Melatonin on Retinal Ganglion Cells in Rats

    Institute of Scientific and Technical Information of China (English)

    TANG Qiongyan; HU Yizhen; CAO Yang

    2006-01-01

    To investigate the neuroprotective effect of melatonin (MT) on retinal ganglion cells (RGCs) in rats with ischemia reperfusion injury (RIR), 24 healthy SD rats were randomly divided into two groups:group A and group B. RIR model was induced in the left eyes by increasing the pressure of the anterior chamber. Group A was treated with 10 % alcohol- normal saline (1 mL/kg/d, ip), while group B was treated with 0.5 % MT (1 mL/kg/d, ip). On the basis of the time interval between the left eyes RIR and the sacrifice, rats in both group A and group B were further divided into 3 subgroups: groups A1 and B1 (days 7), groups A2 and B2 (days 14), groups A3 and B3 (days 30), with4 rats in each subgroup. 7 day before the sacrifice, 3 % fluorogold was bilaterally injected into superior colliculi and geniculate body. The eyes were enucleated after being sacrificed, and mounting of the retina from both eyes was performed on a slide and observed under a fluorescence microscope. Four photos were taken from each of the four quadrants of the retina.The labeled-RGCs were counted by using a computerized image analyzer. The rate of the labeledRGCs was used for statistical analysis. Our results showed that, in group A, the rate of the labeled-RGCs was (77. 16±6.35) %, (65.53±7.01) %, (53.85±4.38) % on day 7, 14 and 30.In group B, the rate of the labeled-RGCs was (81.33±9.27) %, (79.80±8.36) %, (80.34±11.05) % on day 7, 14 and 30. In group B, which was treated with MT after RIR, the rate of labeled-RGCs was significantly higher than that of group A on day 14 and day 30 (P<0.05). It is concluded that, in the RIR rats, MT therapy could increase the survival rate of the RGCs and could rescue and restore the injured RGCs.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Morphology, dendritic field size, somal size, density, and coverage of M and P retinal ganglion cells of dichromatic Cebus monkeys.

    Science.gov (United States)

    Yamada, E S; Silveira, L C; Perry, V H

    1996-01-01

    Male Cebus monkeys are all dichromats, but about two thirds of the females are trichromats. M and P retinal ganglion cells were studied in the male Cebus monkey to investigate the relationship of their morphology to retinal eccentricity. Retinal ganglion cells were retrogradely labeled after optic nerve deposits of biocytin to reveal their entire dendritic tree. Cebus M and P ganglion cell morphology revealed by biocytin retrograde filling is similar to that described for macaque and human M and P ganglion cells obtained by in vitro intracellular injection of HRP and neurobiotin. We measured 264 and 441 M and P ganglion cells, respectively. M ganglion cells have larger dendritic field and cell body size than P ganglion cells at any comparable temporal or nasal eccentricity. Dendritic trees of both M and P ganglion cells are smaller in the nasal than in the temporal region at eccentricities greater than 5 mm and 2 mm for M and P ganglion cells, respectively. The depth of terminal dendrites allows identification of both inner and outer subclasses of M and P ganglion cells. The difference in dendritic tree size between inner and outer cells is small or absent. Comparison between Cebus and Macaca shows that M and P ganglion cells have similar sizes in the central retinal region. The results support the view that M and P pathways are similarly organized in diurnal dichromat and trichromat primates.

  3. Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration.

    Directory of Open Access Journals (Sweden)

    Violeta Gómez-Vicente

    Full Text Available Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss.

  4. Detecting Determinism in Firing Activities of Retinal Ganglion Cells during Response to Complex Stimuli

    Institute of Scientific and Technical Information of China (English)

    CAI Chao-Feng; ZHANG Ying-Ying; LIU Xue; LIANG Pei-Ji; ZHANG Pu-Ming

    2008-01-01

    Complex stimuli are used to probe the response properties of the chicken's retinal ganglion cells (GCs). Thecorrelation dimension method and the nonlinear forecasting method are applied to detect the determinism in the firing activities of the retinal GCs during response to complex stimuli.The inter-spike interval (ISI) series and the first difference of the ISI (DISI) series are analysed.Two conclusions are drawn.Firstly,the first difference operation of the ISI series makes it comparatively easier for determinism detection in the firing activities of retinal GCs.Secondly,the nonlinear forecasting method is more efficient and reliable than the correlation dimension method for determinism detection.

  5. 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.

  6. Postconditioning with inhaled hydrogen promotes survival of retinal ganglion cells in a rat model of retinal ischemia/reperfusion injury.

    Science.gov (United States)

    Wang, Ruobing; Wu, Jiangchun; Chen, Zeli; Xia, Fangzhou; Sun, Qinglei; Liu, Lin

    2016-02-01

    Retinal ischemia/reperfusion (I/R) injury plays a crucial role in the pathophysiology of various ocular diseases. Intraperitoneal injection or ocular instillation with hydrogen (H2)-rich saline was recently shown to be neuroprotective in the retina due to its anti-oxidative and anti-inflammatory effects. Our study aims to explore whether postconditioning with inhaled H2 can protect retinal ganglion cells (RGCs) in a rat model of retinal I/R injury. Retinal I/R injury was performed on the right eyes of rats and was followed by inhalation of 67% H2 mixed with 33% oxygen immediately after ischemia for 1h daily for one week. RGC density was counted using haematoxylin and eosin (HE) staining and retrograde labeling with cholera toxin beta (CTB). Visual function was assessed using flash visual evoked potentials (FVEP) and pupillary light reflex (PLR). Potential biomarkers of retinal oxidative stress and inflammatory responses were measured, including the expression of 4-Hydroxynonenalv (4-HNE), interleukin-1 beta (IL1-β) and tumor necrosis factor alpha (TNF-α). HE and CTB tracing showed that the survival rate of RGCs in the H2-treated group was significantly higher than the rate in the I/R group. Rats with H2 inhalation showed better visual function in assessments of FVEP and PLR. Moreover, H2 treatment significantly decreased the number of 4-HNE-stained cells in the ganglion cell layer and inhibited the retinal overexpression of IL1-β and TNF-α that was induced by retinal I/R injury. Our results demonstrate that postconditioning with inhaled high-dose H2 appears to confer neuroprotection against retinal I/R injury via anti-oxidative, anti-inflammatory and anti-apoptosis pathways.

  7. KR-31378, a potassium-channel opener, induces the protection of retinal ganglion cells in rat retinal ischemic models.

    Science.gov (United States)

    Choi, Anho; Choi, Jun-Sub; Yoon, Yone-Jung; Kim, Kyung-A; Joo, Choun-Ki

    2009-04-01

    KR-31378 is a newly developed K(ATP)-channel opener. To investigate the ability of KR-31378 to protect retinal ganglion cells (RGC), experiments were conducted using two retinal ischemia models. Retinal ischemia was induced by transient high intraocular pressure (IOP) for acute ischemia and by three episcleral vein occlusion for chronic retinal ischemia. KR-31378 was injected intraperitoneally and administered orally in the acute and chronic ischemia models, respectively. Under the condition of chronic ischemia, RGC density in the KR-31378-treated group was statistically higher than that in the non-treated group, and IOP was reduced. In the acute retinal ischemia model, 90% of RGC were degenerated after one week in non-treated retina, but, RGC in KR-31378-treated retina were protected from ischemic damage in a dose-dependent manner and showed inhibited glial fibrillary acidic protein (GFAP) expression. Furthermore, the KR-31378 protective effect was inhibited by glibenclamide treatment in acute ischemia. These findings indicate that systemic KR-31378 treatment may protect against ischemic injury-induced ganglion cell loss in glaucoma.

  8. The antibiotic neomycin abolishes directional selectivity in rabbit retinal ganglion cells.

    Science.gov (United States)

    Jensen, R J

    1996-12-01

    1. Extracellular recordings from ON/OFF directionally selective ganglion cells in superfused rabbit retinas were made to study the effect of the aminoglycoside antibiotic, neomycin, on the responses of these cells to a moving light stimulus. 2. Neomycin, at 480-800 microM, reversibly abolished the directional selectivity in these ganglion cells by bringing out a response to movement in one ("null") direction that was similar in magnitude to the response to movement in the reverse ("preferred") direction. 3. Gentamicin, streptomycin, and tobramycin were also able to abolish directional selectivity in these ganglion cells but only at concentrations greater than 1000 microM. 4. It is proposed that neomycin abolishes directional selectivity in rabbit retinal ganglion cells by blocking omega-conotoxin MVIIC-sensitive Ca2+ channels in the retina.

  9. Population activity changes during a trial-to-trial adaptation of bullfrog retinal ganglion cells.

    Science.gov (United States)

    Ding, Wei; Xiao, Lei; Jing, Wei; Zhang, Pu-Ming; Liang, Pei-Ji

    2014-07-09

    A 'trial-to-trial adaptation' of bullfrog retinal ganglion cells in response to a repetitive light stimulus was investigated in the present study. Using the multielectrode recording technique, we studied the trial-to-trial adaptive properties of ganglion cells and explored the activity of population neurons during this adaptation process. It was found that the ganglion cells adapted with different degrees: their firing rates were decreased in different extents from early-adaptation to late-adaptation stage, and this was accompanied by a decrease in cross-correlation strength. In addition, adaptation behavior was different for ON-response and OFF-response, which implied that the mechanism of the trial-to-trial adaptation might involve bipolar cells and/or their synapses with other neurons and the stronger adaptation in the ganglion cells' OFF-responses might reflect the requirement to avoid possible saturation in the OFF circuit.

  10. Internalization and synaptogenic effect of GH in retinal ganglion cells (RGCs).

    Science.gov (United States)

    Fleming, Thomas; Martínez-Moreno, Carlos G; Mora, Janeth; Aizouki, Miray; Luna, Maricela; Arámburo, Carlos; Harvey, Steve

    2016-08-01

    In the chicken embryo, GH gene expression occurs in the neural retina and retinal GH promotes cell survival and induces axonal growth of retinal ganglion cells. Neuroretinal GH is therefore of functional importance before the appearance of somatotrophs and the onset of pituitary GH secretion to the peripheral plasma (at ED15-17). Endocrine actions of pituitary GH in the development and function of the chicken embryo eye are, however, unknown. This possibility has therefore been investigated in ED15 embryos and using the quail neuroretinal derived cell line (QNR/D). During this research, we studied for the first time, the coexistence of exogenous (endocrine) and local GH (autocrine/paracrine) in retinal ganglion cells (RGCs). In ovo systemic injections of Cy3-labeled GH demonstrated that GH in the embryo bloodstream was translocated into the neural retina and internalized into RGC's. Pituitary GH may therefore be functionally involved in retinal development during late embryogenesis. Cy3-labelled GH was similarly internalized into QNR/D cells after its addition into incubation media. The uptake of exogenous GH was by a receptor-mediated mechanism and maximal after 30-60min. The exogenous (endocrine) GH induced STAT5 phosphorylation and increased growth associated protein 43 (GAP43) and SNAP-25 immunoreactivity. Ex ovo intravitreal injections of Cy3-GH in ED12 embryos resulted in GH internalization and STAT5 activation. Interestingly, the CY3-labeled GH accumulated in perinuclear regions of the QNR/D cells, but was not found in the cytoplasm of neurite outgrowths, in which endogenous retinal GH is located. This suggests that exogenous (endocrine) and local (autocrine/paracrine) GH are both involved in retinal function in late embryogenesis but they co-exist in separate intracellular compartments within retinal ganglion cells.

  11. Role of calcium conductance in firing behavior of retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    Dan Wang; Qingli Qiao; Nan Xie

    2011-01-01

    Fohlmeister-Coleman-Miller model of retinal ganglion cells consists of five ion channels; these are sodium channels, calcium channels, and 3 types of potassium channels. An increasing number of studies have investigated sodium channels, voltage-gated potassium channels, and delayed rectifier potassium channels. However, little is known about calcium channels, and in particular the dynamics and computational models of calcium ions. Retinal prostheses have been designed to assist with sight recovery for the blind, and in the present study, the effects of calcium ions in retinal ganglion cell models were analyzed with regard to calcium channel potential and calcium-activated potassium potential. Using MATLAB software, calcium conductance and calcium current from the Fohlmeister-Coleman-Miller model, under clamped voltages, were numerically computed using backward Euler methods. Subsequently, the Fohlmeister-Coleman-Miller model was simulated with the absence of calcium-current (lc,) or calcium-activated potassium current (IK, ca). The model was also analyzed according to the phase plane method.The relationship curve between peak calcium current and clamped potentials revealed an inverted bell shape, and the calcium-activated potassium current increased the frequency of firing and the peak of membrane potential. Results suggested that calcium ion concentrations play an important role in controlling the peak and the magnitude of peak membrane voltage in retinal ganglion cells.

  12. Retrograde degeneration of retinal ganglion cells in homonymous hemianopsia

    OpenAIRE

    Herro AM; Lam BL

    2015-01-01

    Angela M Herro, Byron L Lam Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, USA Background: The aim of this study was to demonstrate the relationship between topographic reduction in macular ganglion cell complex (GCC) thickness as detected with spectral-domain optical coherence tomography and visual field defects caused by ischemic occipital cortical injury.Methods: This study was a retrospective review of all pat...

  13. Effects of low level laser treatment on the survival of axotomized retinal ganglion cells in adult Hamsters

    Institute of Scientific and Technical Information of China (English)

    Kwok-Fai So; Mason Chin Pang Leung; Qi Cui

    2014-01-01

    Injury to axons close to the neuronal bodies in the mammalian central nervous system causes a large proportion of parenting neurons to degenerate. It is known that optic nerve transection close to the eye in rodents leads to a loss of about half of retinal ganglion cells in 1 week and about 90% in 2 weeks. Using low level laser treatment in the present study, we demonstrated that treatment with helium-neon (660 nm) laser with 15 mW power could delay retinal ganglion cell death after optic nerve axotomy in adult hamsters. The effect was most apparent in the ifrst week with a short period of treatment time (5 minutes) in which 65–66% of retinal ganglion cells survived the optic nerve axotomy whereas 45–47% of retinal ganglion cells did so in optic nerve axotomy controls. We also found that single dose and early commencement of laser irradiation were important in protecting retinal ganglion cells following optic nerve axotomy. These ifndings thus convincingly show that appropriate laser treatment may be neuroprotective to retinal gan-glion cells.

  14. 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.

  15. Direction selectivity is computed by active dendritic integration in retinal ganglion cells.

    Science.gov (United States)

    Sivyer, Benjamin; Williams, Stephen R

    2013-12-01

    Active dendritic integration is thought to enrich the computational power of central neurons. However, a direct role of active dendritic processing in the execution of defined neuronal computations in intact neural networks has not been established. Here we used multi-site electrophysiological recording techniques to demonstrate that active dendritic integration underlies the computation of direction selectivity in rabbit retinal ganglion cells. Direction-selective retinal ganglion cells fire action potentials in response to visual image movement in a preferred direction. Dendritic recordings revealed that preferred-direction moving-light stimuli led to dendritic spike generation in terminal dendrites, which were further integrated and amplified as they spread through the dendritic arbor to the axon to drive action potential output. In contrast, when light bars moved in a null direction, synaptic inhibition vetoed neuronal output by directly inhibiting terminal dendritic spike initiation. Active dendritic integration therefore underlies a physiologically engaged circuit-based computation in the retina.

  16. Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion.

    Science.gov (United States)

    Becker, Silke; Eastlake, Karen; Jayaram, Hari; Jones, Megan F; Brown, Robert A; McLellan, Gillian J; Charteris, David G; Khaw, Peng T; Limb, G Astrid

    2016-02-01

    Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA). Unlike previous observations in the rat, transplantation of hMGSC-derived RGCs into the feline vitreous formed aggregates and elicited a severe inflammatory response without improving visual function. In contrast, allogeneic transplantation of feline MGSC (fMGSC)-derived RGCs into the vitrectomized eye improved the scotopic threshold response (STR) of the electroretinogram (ERG). Despite causing functional improvement, the cells did not attach onto the retina and formed aggregates on peripheral vitreous remnants, suggesting that vitreous may constitute a barrier for cell attachment onto the retina. This was confirmed by observations that cellular scaffolds of compressed collagen and enriched preparations of fMGSC-derived RGCs facilitated cell attachment. Although cells did not migrate into the RGC layer or the optic nerve, they significantly improved the STR and the photopic negative response of the ERG, indicative of increased RGC function. These results suggest that MGSCs have a neuroprotective ability that promotes partial recovery of impaired RGC function and indicate that cell attachment onto the retina may be necessary for transplanted cells to confer neuroprotection to the retina. Significance: Müller glia with stem cell characteristics are present in the adult human retina, but they do not have regenerative ability. These cells, however, have potential for

  17. Density, proportion, and dendritic coverage of retinal ganglion cells of the common marmoset (Callithrix jacchus jacchus

    Directory of Open Access Journals (Sweden)

    F.L. Gomes

    2005-06-01

    Full Text Available We performed a quantitative analysis of M and P cell mosaics of the common-marmoset retina. Ganglion cells were labeled retrogradely from optic nerve deposits of Biocytin. The labeling was visualized using horseradish peroxidase (HRP histochemistry and 3-3'diaminobenzidine as chromogen. M and P cells were morphologically similar to those found in Old- and New-World primates. Measurements were performed on well-stained cells from 4 retinas of different animals. We analyzed separate mosaics for inner and outer M and P cells at increasing distances from the fovea (2.5-9 mm of eccentricity to estimate cell density, proportion, and dendritic coverage. M cell density decreased towards the retinal periphery in all quadrants. M cell density was higher in the nasal quadrant than in other retinal regions at similar eccentricities, reaching about 740 cells/mm² at 2.5 mm of temporal eccentricity, and representing 8-14% of all ganglion cells. P cell density increased from peripheral to more central regions, reaching about 5540 cells/mm² at 2.5 mm of temporal eccentricity. P cells represented a smaller proportion of all ganglion cells in the nasal quadrant than in other quadrants, and their numbers increased towards central retinal regions. The M cell coverage factor ranged from 5 to 12 and the P cell coverage factor ranged from 1 to 3 in the nasal quadrant and from 5 to 12 in the other quadrants. These results show that central and peripheral retinal regions differ in terms of cell class proportions and dendritic coverage, and their properties do not result from simply scaling down cell density. Therefore, differences in functional properties between central and peripheral vision should take these distinct regional retinal characteristics into account.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Spontaneous oscillatory rhythms in the degenerating mouse retina modulate retinal ganglion cell responses to electrical stimulation

    Directory of Open Access Journals (Sweden)

    Yong Sook eGoo

    2016-01-01

    Full Text Available Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD and retinitis pigmentosa (RP, but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice, where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs. Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties.

  4. Alpha B-crystallin improved survival of retinal ganglion cells in a rat model of acute ocular hypertension

    Institute of Scientific and Technical Information of China (English)

    Zhihong Wu; Layi Wang; Shike Hou

    2012-01-01

    Increased endogenous αB-crystallin protein levels have been shown to reduce cell apoptosis,although the effects of exogenous αB-crystallin protein remain poorly understood.The present study established an acute ocular hypertension model in the right eye of Sprague-Dawley rats.Fluorogold retrograde tracing and immunofluorescence methods showed that the number of retinal ganglion cells decreased in the right eyes and caspase-3 expression increased following acute ocular hypertension.Intravitreal injection of αB-crystallin in the right eye increased the number of retinal ganglion cells and reduced caspase-3 expression.Results demonstrated that exogenous αB-crystallin protein inhibited caspase-3 expression and improved retinal ganglion cell survival following acute ocular hypertension.

  5. Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

    Science.gov (United States)

    Madeira, Maria H.; Ortin-Martinez, Arturo; Nadal-Nícolas, Francisco; Ambrósio, António F.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Santiago, Ana Raquel

    2016-01-01

    Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma. PMID:27270337

  6. Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Liping Yang; Lemeng Wu; Dongmei Wang; Ying Li; Hongliang Dou; Mark OMTso; Zhizhong Ma

    2013-01-01

    Endoplasmic reticulum stress is closely involved in the early stage of diabetic retinopathy. In the present study, a streptozotocin-induced diabetic animal model was given an intraperitoneal injection of tauroursodeoxycholic acid. Results from immunofluorescent co-localization experiments showed that both caspase-12 protein and c-Jun N-terminal kinase 1 phosphorylation levels significantly in-creased, which was associated with retinal ganglion celldeath in diabetic retinas. The C/ERB ho-mologous protein pathway directly contributed to glial reactivity, and was subsequently responsible for neuronal loss and vascular abnormalities in diabetic retinopathy. Our experimental findings in-dicate that endoplasmic reticulum stress plays an important role in diabetes-induced retinal neu-ronal loss and vascular abnormalities, and that inhibiting the activation of the endoplasmic reticulum stress pathway provides effective protection against diabetic retinopathy.

  7. 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.

  8. Retinal Arterial Occlusive Disease in a Young Patient with Cat Scratch Disease

    OpenAIRE

    Georgios Batsos; Kabanarou, Stamatina A.; Pantelis Fotiou; Alexandros Rouvas; Tina Xirou

    2013-01-01

    Purpose: To report an unusual case of a branch retinal arterial occlusion and bilateral multifocal retinitis in a young woman with cat scratch disease. Methods: A 23-year-old woman was referred to our clinic complaining of a sudden scotoma in the upper part of the visual field of her left eye. Fundoscopy revealed occlusion of an inferior temporal branch of the retinal artery in the left eye and bilateral multifocal retinitis, which was confirmed by fluorescein angiography. Subsequent indocyan...

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

    Science.gov (United States)

    Hannibal, J; Kankipati, L; Strang, C E; Peterson, B B; Dacey, D; Gamlin, P D

    2014-07-01

    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). The ipRGCs regulate other nonimage-forming visual functions such as the pupillary light reflex, masking behavior, and light-induced melatonin suppression. To evaluate whether PACAP-immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we characterized the occurrence of PACAP in melanopsin-expressing ipRGCs and in the retinal target areas in the brain visualized by the anterograde tracer cholera toxin subunit B (CtB) in combination with PACAP staining. In the retina, PACAP and melanopsin were found to be costored in 99% of melanopsin-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 including the pregeniculate nucleus, the pretectal olivary nucleus, the nucleus of the optic tract, the brachium of the superior colliculus, and the superior colliculus. In conclusion, PACAP-immunoreactive projections with colocalized CtB represent retinal projections of ipRGCs in the macaque monkey, supporting previous retrograde tracer studies demonstrating that melanopsin-containing retinal projections reach areas in the primate brain involved in both image- and nonimage-forming visual processing.

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

    Science.gov (United States)

    Hannibal, J.; Kankipati, L.; Strang, C.E.; Peterson, B.B.; Dacey, D.; Gamlin, P.D.

    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 PACAP. The ipRGCs regulate other non-image-forming visual functions such as the pupillary light reflex, masking behaviour and light induced melatonin suppression. To evaluate whether PACAP immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we characterized the occurrence of PACAP in melanopsin expressing ipRGCs and in the retinal target areas in the brain visualized by the anterograde tracer Cholera Toxin subunit B (CtB) in combination with PACAP staining. In the retina, PACAP and melanopsin were found to be co-stored in 99% of melanopsin 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 co-localized CtB and PACAP immunostaining were identified in the SCN, the lateral geniculate complex (LGN) including the pregeniculate nucleus (PrGC), the pretectal olivary nucleus (PON), the nucleus of the optic tract (NOT), the brachium of the superior colliculus (BSC), and the superior colliculus (SC). In conclusion, PACAP immunoreactive projections with co-localized CtB represent retinal projections of ipRGCs in the macaque monkey, and support previous retrograde tracer studies demonstrating that melanopsin containing retinal projections reach areas in the primate brain involved in both image and non-image-forming visual processing. PMID:24752373

  11. Retinal Arterial Occlusive Diseasein a Young Patient with Cat Scratch Disease

    Directory of Open Access Journals (Sweden)

    Georgios Batsos

    2013-08-01

    Full Text Available Purpose: To report an unusual case of a branch retinal arterial occlusion and bilateral multifocal retinitis in a young woman with cat scratch disease. Methods: A 23-year-old woman was referred to our clinic complaining of a sudden scotoma in the upper part of the visual field of her left eye. Fundoscopy revealed occlusion of an inferior temporal branch of the retinal artery in the left eye and bilateral multifocal retinitis, which was confirmed by fluorescein angiography. Subsequent indocyanine angiography did not reveal choroidal involvement. Laboratory analysis showed rising IgG titers for Bartonellahenselae. Results: Cat scratch disease was diagnosed, and a 4-week course of doxycycline was initiated. The patient responded well to the antibiotics. Both retinitis and arterial occlusion were resolved, the visual field was regained and the patient reported elimination of her symptoms. Conclusions: Cat scratch disease should be considered in the differential diagnosis in young patients with retinal occlusive disease.

  12. Epigenetic intervention with a BET inhibitor ameliorates acute retinal ganglion cell death in mice

    Science.gov (United States)

    Li, Jun; Zhao, Lei; Urabe, Go; Fu, Yingmei

    2017-01-01

    Purpose The bromo and extraterminal (BET) epigenetic “reader” family is becoming an appealing new therapeutic target for several common diseases, yet little is known of its role in retinal neurodegeneration. We explored the potential of BET inhibition in the protection of retinal ganglion cells (RGCs). Methods To test the therapeutic effect of JQ1, an inhibitor highly selective for the BET family of proteins, we used an acute RGC damage model induced by N-methyl-D-aspartic acid (NMDA) excitotoxicity. Adult C57BL/6 mice received an intravitreal injection of NMDA with (or without) JQ1 in one eye and vehicle control in the contralateral eye; RGC loss was assessed on retinal sections and whole mounts. Gene expression and apoptosis were analyzed by quantitative real time (RT)-PCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), respectively. For counting RGCs, immunostaining of the marker protein BRN3A was performed on whole mounts. Results NMDA treatment eliminated RGCs (day 7 and day 14 post injection) and diminished the expression (mRNAs) of RGC-selective genes, including Thy1, Nrn1, Sncg, and Nfl (day 3 and day 7). In contrast, co-injection with JQ1 maintained the number and gene expression of RGCs at ~2 fold of the control (NMDA only, no JQ1), and it decreased NMDA-induced TUNEL-positive cells in the RGC layer by 35%. While NMDA treatment dramatically upregulated mRNAs of inflammatory cytokines (TNFα, IL-1β, MCP-1, RANTES) in retinal homogenates, co-injection with JQ1 suppressed their upregulation by ~50%. Conclusions Intravitreal injection of a BET inhibitor (JQ1) ameliorates NMDA-induced RGC death, revealing the RGC-protective potential of pharmacological blockage of the BET family. This new strategy of epigenetic intervention may be extended to other retinal degenerative conditions. PMID:28356707

  13. Human organotypic retinal cultures (HORCs) as a chronic experimental model for investigation of retinal ganglion cell degeneration.

    Science.gov (United States)

    Osborne, Andrew; Hopes, Marina; Wright, Phillip; Broadway, David C; Sanderson, Julie

    2016-02-01

    There is a growing need for models of human diseases that utilise native, donated human tissue in order to model disease processes and develop novel therapeutic strategies. In this paper we assessed the suitability of adult human retinal explants as a potential model of chronic retinal ganglion cell (RGC) degeneration. Our results confirmed that RGC markers commonly used in rodent studies (NeuN, βIII Tubulin and Thy-1) were appropriate for labelling human RGCs and followed the expected differential expression patterns across, as well as throughout, the macular and para-macular regions of the retina. Furthermore, we showed that neither donor age nor post-mortem time (within 24 h) significantly affected the initial expression levels of RGC markers. In addition, the feasibility of using human post mortem donor tissue as a long-term model of RGC degeneration was determined with RGC protein being detectable up to 4 weeks in culture with an associated decline in RGC mRNA and significant, progressive, apoptotic labelling of NeuN(+) cells. Differences in RGC apoptosis might have been influenced by medium compositions indicating that media constituents could play a role in supporting axotomised RGCs. We propose that using ex vivo human explants may prove to be a useful model for testing the effectiveness of neuroprotective strategies.

  14. Neuroprotective effects of ClC-3 chloride channel in glutamate-induced retinal ganglion cell RGC-5 apoptosis

    Institute of Scientific and Technical Information of China (English)

    Li Yu; Ning Han; Ligang Jiang; Yajuan Zheng; Lifeng Liu

    2011-01-01

    Transforming growth factor β plays a role in regulation of apoptosis in ClC-3 and the Smads signaling pathway, although the underlying mechanisms remain unclear. The present study determined possible signal transduction mechanisms based on CIC-3 expression, which accordingly affected apoptosis of retinal ganglion cells in a glutamate-induced retinal ganglion cell RGC-5 apoptosis model. Results revealed significantly increased cell survival rate and significantly decreased apoptosis rate following apoptosis of ClC-3 cDNA-transfected glutamate-induced retinal ganglion cells. Following inhibition of the ClC-3 chloride channel using RNAi technology, cell survival and apoptosis rates were reversed. In addition, expression of transforming growth factor β2, Smads2, Smads3, Smads4, and Smads7 increased to varying degrees. These results suggest that ClC-3 chloride channel plays a protective role in glutamate-induced apoptosis of retinal ganglion cells, and transforming growth factor β/Smads signal transduction pathways are involved in this process.

  15. Pan-retinal characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

    Science.gov (United States)

    Hilgen, Gerrit; Pirmoradian, Sahar; Pamplona, Daniela; Kornprobst, Pierre; Cessac, Bruno; Hennig, Matthias H.; Sernagor, Evelyne

    2017-01-01

    We have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to different contrasts not only revealed a complex developmental profile for ON, OFF and ON-OFF responses, but also unveiled differences between dorsal and ventral RGC responses. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental profile of ON and OFF responses exhibited antagonistic behaviour, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive field (RF) center sizes decrease, spike-triggered averaged responses to white noise become stronger, and centers become more circular while maintaining differences between RGC types. We conclude that the maturation of retinal functionality is not spatially homogeneous, likely reflecting ecological requirements that favour earlier maturation of the dorsal retina. PMID:28186129

  16. Decoding of retinal ganglion cell spike trains evoked by temporally patterned electrical stimulation.

    Science.gov (United States)

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

    2010-08-12

    For successful restoration of vision by retinal prostheses, the neural activity of retinal ganglion cells (RGCs) evoked by electrical stimulation should represent the information of spatiotemporal patterns of visual input. We propose a method to evaluate the effectiveness of stimulation pulse trains so that the crucial temporal information of a visual input is accurately represented in the RGC responses as the amplitudes of pulse trains are modulated according to the light intensity. This was enabled by spike train decoding. The effectiveness of the stimulation was evaluated by the accuracy of decoding pulse amplitude from the RGC spike train, i.e., by the similarity between the original and the decoded pulse amplitude time series. When the parameters of stimulation were suitably determined, the RGC responses were reliably modulated by varying the amplitude of electrical pulses. Accordingly, the temporal pattern of pulse amplitudes could be successfully decoded from multiunit RGC spike trains. The range of pulse amplitude and the pulse rate were critical for accurate representation of input information in RGC responses. These results suggest that pulse amplitude modulation is a feasible means to encode temporal visual information by RGC spike trains and thus to implement stimulus encoding strategies for retinal prostheses.

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

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    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

  18. Protection of retinal ganglion cells and retinal vasculature by Lycium barbarum polysaccharides in a mouse model of acute ocular hypertension.

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    Xue-Song Mi

    Full Text Available Acute ocular hypertension (AOH is a condition found in acute glaucoma. The purpose of this study is to investigate the protective effect of Lycium barbarum polysaccharides (LBP and its protective mechanisms in the AOH insult. LBP has been shown to exhibit neuroprotective effect in the chronic ocular hypertension (COH experiments. AOH mouse model was induced in unilateral eye for one hour by introducing 90 mmHg ocular pressure. The animal was fed with LBP solution (1 mg/kg or vehicle daily from 7 days before the AOH insult till sacrifice at either day 4 or day 7 post insult. The neuroprotective effects of LBP on retinal ganglion cells (RGCs and blood-retinal-barrier (BRB were evaluated. In control AOH retina, loss of RGCs, thinning of IRL thickness, increased IgG leakage, broken tight junctions, and decreased density of retinal blood vessels were observed. However, in LBP-treated AOH retina, there was less loss of RGCs with thinning of IRL thickness, IgG leakage, more continued structure of tight junctions associated with higher level of occludin protein and the recovery of the blood vessel density when compared with vehicle-treated AOH retina. Moreover, we found that LBP provides neuroprotection by down-regulating RAGE, ET-1, Aβ and AGE in the retina, as well as their related signaling pathways, which was related to inhibiting vascular damages and the neuronal degeneration in AOH insults. The present study suggests that LBP could prevent damage to RGCs from AOH-induced ischemic injury; furthermore, through its effects on blood vessel protection, LBP would also be a potential treatment for vascular-related retinopathy.

  19. Specific projection of displaced retinal ganglion cells upon the accessory optic system in the pigeon (Columbia livia).

    Science.gov (United States)

    Karten, J H; Fite, K V; Brecha, N

    1977-04-01

    In the pigeon, the nucleus of the basal optic root, a component of the accessory optic system, projects directly upon the vestibulo-cerebellum. This nucleus receives a prominent projection composed of large-diameter retinal axons, known as the basal optic root. The cells of origin of this tract were identified using horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) as a retrograde marker. Injections of horseradish peroxidase confined primarily to the basal optic root nucleus labeled displaced ganglion cells of the contralateral retina. Cell sizes were 18-30 micronm and the dendrites of these cells were confined to the first stratum of the inner plexiform layer. Approximately 3700 displaced ganglion cells were labeled after injections of horseradish peroxidase into basal optic root. In contrast, no displaced ganglion cells were labeled after injections of horseradish peroxidase into the optic tectum, which labeled only cells in the ganglion cell layer proper. These findings indicate that displaced ganglion cells constitute a unique population of retinal neurons that give rise to a bisynaptic pathway directed to the cerebellum via the nucleus of the basal optic root. These displaced ganglion cells may play a major role inoculomotor reflexes.

  20. Retrograde Labeling of Adult Rat Retinal Ganglion Cells with the Flurogold

    Institute of Scientific and Technical Information of China (English)

    Wei Huang; Yannian Hui; Miaoli Zhang

    2000-01-01

    Purpose: To study the densities and distribution of retinal ganglion cells(RGC) in adult rat retinae with flurogold(FG) labeling retogradely.Methods: FG was injected to the superior colliculi(SC) and dorsal lateral geniculate nuclei (dLGN) in adult rats and the retinae were examined by fluorescence microscopy at various periods of time.Results: FG-labelled RGC were observed in the retina as early as 3 days after application of FG. The labelled cells gradually increased in density, reached 95% of the maximal number on days 7 and the maximal number on days 30. The density of labelled cells was higher in the posterior pole than in the peripheral area. The fluorescence intensity in labelled cells maintained up to 60 days.Conclusion: The FG retrograde labeling method is reliable and effective for quantity of RGC. Eye Science 2000; 16:29 ~ 33.

  1. Retrograde Labeling of Adult Rat Retinal Ganglion Cells with the Flurogold

    Institute of Scientific and Technical Information of China (English)

    WeiHuang; YannianHui; 等

    2002-01-01

    Purpose:To study the densities and distribution of retinal ganglion cells(RGC) in adult rat retinae with flurogold(FG) labeling retogradely.Methods:FG was injected to the superior colliculid(SC) and dorsal lateral geniculate nuclei(dLGN) in adult rats and the retinae were examined by fluorescence microscopy at various periods of time.Results:FG-labelled RGC were observed in the retina as early as 3 days after application of FG.The labeled cells gradually increased in density,reached 95% of the maximal number on days 7 and the maximal nuber on days 30.The density of labeled cells was higher in the posterior pole than in the peripheral area.The fluorescence intensity in labeled cells maintained up to 60 days.Conclusion:The FG retrograde labeling method is reliable and effective for quantity of RGC.Eye Science 2000;46:29-33.

  2. Properties of mouse retinal ganglion cell dendritic growth during postnatal development

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The property of dendritic growth dynamics during development is a subject of intense interest.Here,we investigated the dendritic motility of retinal ganglion cells (RGCs) during different developmental stages,using ex vivo mouse retina explant culture,Semliki Forest Virus transfection and time-lapse observations.The results illustrated that during development,the dendritic motility underwent a change from rapid growth to a relatively stable state,i.e.,at P0 (day of birth),RGC dendrites were in a highly active state,whereas at postnatal 13 (P13) they were more stable,and at P3 and P8,the RGCs were in an intermediate state.At any given developmental stage,RGCs of different types displayed the same dendritic growth rate and extent.Since the mouse is the most popular mammalian model for genetic manipulation,this study provided a methodological foundation for further exploring the regulatory mechanisms of dendritic development.

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

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    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

  4. Regenerative Responses and Axon Pathfinding of Retinal Ganglion Cells in Chronically Injured Mice

    Science.gov (United States)

    Yungher, Benjamin J.; Ribeiro, Márcio; Park, Kevin K.

    2017-01-01

    Purpose Enhanced regeneration of retinal ganglion cell (RGC) axons can be achieved by modification of numerous neuronal-intrinsic factors. However, axon growth initiation and the pathfinding behavior of these axons after traumatic injury remain poorly understood outside of acute injury paradigms, despite the clinical relevance of more chronic settings. We therefore examined RGC axon regeneration following therapeutic delivery that is postponed until 2 months after optic nerve crush injury. Methods Optic nerve regeneration was induced by virally mediated (adeno-associated virus) ciliary neurotrophic factor (AAV-CNTF) administered either immediately or 56 days after optic nerve crush in wild-type or Bax knockout (KO) mice. Retinal ganglion nerve axon regeneration was assessed 21 and 56 days after viral injection. Immunohistochemical analysis of RGC injury signals and extrinsic factors in the optic nerve were also examined at 5 and 56 days post crush. Results In addition to sustained expression of injury response proteins in surviving RGCs, we observe axon regrowth in wild-type and apoptosis-deficient Bax KO mice following AAV-CNTF treatment. Fewer instances of aberrant axon growth are seen, at least in the area near the lesion site, in animals given treatment 56 days after crush injury compared to the animals given treatment immediately after injury. We also find evidence of long distance growth into a visual target in Bax KO mice despite postponed initiation of this regenerative program. Conclusions These studies provide evidence against an intrinsic critical period for RGC axon regeneration or degradation of injury signals. Regeneration results from Bax KO mice imply highly sustained regenerative capacity in RGCs, highlighting the importance of long-lasting neuroprotective strategies as well as of RGC axon guidance research in chronically injured animals. PMID:28324115

  5. 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.

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

    Institute of Scientific and Technical Information of China (English)

    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 informationtheoretic 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.%@@ 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.

  7. 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.

  8. Implementing dynamic clamp with synaptic and artificial conductances in mouse retinal ganglion cells.

    Science.gov (United States)

    Huang, Jin Y; Stiefel, Klaus M; Protti, Dario A

    2013-05-16

    Ganglion cells are the output neurons of the retina and their activity reflects the integration of multiple synaptic inputs arising from specific neural circuits. Patch clamp techniques, in voltage clamp and current clamp configurations, are commonly used to study the physiological properties of neurons and to characterize their synaptic inputs. Although the application of these techniques is highly informative, they pose various limitations. For example, it is difficult to quantify how the precise interactions of excitatory and inhibitory inputs determine response output. To address this issue, we used a modified current clamp technique, dynamic clamp, also called conductance clamp (1, 2, 3) and examined the impact of excitatory and inhibitory synaptic inputs on neuronal excitability. This technique requires the injection of current into the cell and is dependent on the real-time feedback of its membrane potential at that time. The injected current is calculated from predetermined excitatory and inhibitory synaptic conductances, their reversal potentials and the cell's instantaneous membrane potential. Details on the experimental procedures, patch clamping cells to achieve a whole-cell configuration and employment of the dynamic clamp technique are illustrated in this video article. Here, we show the responses of mouse retinal ganglion cells to various conductance waveforms obtained from physiological experiments in control conditions or in the presence of drugs. Furthermore, we show the use of artificial excitatory and inhibitory conductances generated using alpha functions to investigate the responses of the cells.

  9. Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

    Science.gov (United States)

    Liu, Ruixing; Wang, Yanling; Pu, Mingliang

    2016-01-01

    Purpose This study was conducted to determine whether alpha lipoic acid (ALA) promotes the survival of retinal ganglion cells (RGCs) in a rat model of optic nerve crush (ONC) injury and to investigate the neuroprotective mechanisms of ALA in the retina in this ONC injury model. Methods Adult male Sprague-Dawley rats (180–220 g) were subjected to ONC injury surgery. ALA (63 mg/kg) was injected intravenously 1 day before or after the ONC injury. Animals were euthanized after 10 days, and the number of ganglion cells positive for RNA-binding protein with multiple splicing (Rbpms), which is an RGC marker, were counted on the whole mount retinas. In addition, immunofluorescence and immunoblotting were performed to examine the localization and levels of erythropoietin receptor (EPOR) and neurotrophin-4/5 (NT4/5) in the retinas in all experimental groups. To determine whether the EPO/EPOR signaling pathway was involved in the ALA antioxidant pathway, the rats were subjected to ruxolitinib (INCB018424, 0.25 mg/kg, bid, intraperitoneal, i.p.) treatment after the animals were injected intravenously with ALA 1 day before ONC injury. Results The average number of Rbpms-positive cells/mm2 in the control group (sham-operated group), the ONC group, the ALA-ONC group, and the ONC-ALA group retinas was 2219±28, 418±8, 848±22, and 613±18/mm2, respectively. The ALA-ONC and ONC-ALA groups showed a statistically significantly increased RGC survival rate compared to the ONC group. There were statistical differences in the RGC survival rates between the ALA-ONC (39%) and ONC-ALA groups (28%; p<0.05). Immunofluorescent labeling showed that EPOR and NT4/5 expression was significant in the retinal ganglion cell layer (GCL). At the same time, western blot analysis revealed that ALA induced upregulation of EPOR protein and NT4/5 protein expression in the retina after ONC injury. However, INCB018424 reversed the protective effects of ALA on the ONC retinas. Conclusions ALA has

  10. Neuroprotection by GH against excitotoxic-induced cell death in retinal ganglion cells.

    Science.gov (United States)

    Martínez-Moreno, Carlos G; Ávila-Mendoza, José; Wu, Yilun; Arellanes-Licea, Elvira Del Carmen; Louie, Marcela; Luna, Maricela; Arámburo, Carlos; Harvey, Steve

    2016-08-01

    Retinal growth hormone (GH) has been shown to promote cell survival in retinal ganglion cells (RGCs) during developmental waves of apoptosis during chicken embryonic development. The possibility that it might also against excitotoxicity-induced cell death was therefore examined in the present study, which utilized quail-derived QNR/D cells as an in vitro RGC model. QNR/D cell death was induced by glutamate in the presence of BSO (buthionine sulfoxamide) (an enhancer of oxidative stress), but this was significantly reduced (PGH (rcGH). Similarly, QNR/D cells that had been prior transfected with a GH plasmid to overexpress secreted and non-secreted GH. This treatment reduced the number of TUNEL-labeled cells and blocked their release of lactate dehydrogenase (LDH). In a further experiment with dissected neuroretinal explants from ED (embryonic day) 10 embryos, rcGH treatment of the explants also reduced (PGH-overexpressing QNR/D cells. As rcGH treatment and GH-overexpression cells also increased the content of IGF-1 and IGF-1 mRNA this neuroprotective action of GH is likely to be mediated, at least partially, through an IGF-1 mechanism. This possibility is supported by the fact that the siRNA knockdown of GH or IGF-1 significantly reduced QNR/D cell viability, as did the immunoneutralization of IGF-1. GH is therefore neuroprotective against excitotoxicity-induced RGC cell death by anti-apoptotic actions involving IGF-1 stimulation.

  11. A general principle governs vision-dependent dendritic patterning of retinal ganglion cells.

    Science.gov (United States)

    Xu, Hong-Ping; Sun, Jin Hao; Tian, Ning

    2014-10-15

    Dendritic arbors of retinal ganglion cells (RGCs) collect information over a certain area of the visual scene. The coverage territory and the arbor density of dendrites determine what fraction of the visual field is sampled by a single cell and at what resolution. However, it is not clear whether visual stimulation is required for the establishment of branching patterns of RGCs, and whether a general principle directs the dendritic patterning of diverse RGCs. By analyzing the geometric structures of RGC dendrites, we found that dendritic arbors of RGCs underwent a substantial spatial rearrangement after eye-opening. Light deprivation blocked both the dendritic growth and the branch patterning, suggesting that visual stimulation is required for the acquisition of specific branching patterns of RGCs. We further showed that vision-dependent dendritic growth and arbor refinement occurred mainly in the middle portion of the dendritic tree. This nonproportional growth and selective refinement suggest that the late-stage dendritic development of RGCs is not a passive stretching with the growth of eyes, but rather an active process of selective growth/elimination of dendritic arbors of RGCs driven by visual activity. Finally, our data showed that there was a power law relationship between the coverage territory and dendritic arbor density of RGCs on a cell-by-cell basis. RGCs were systematically less dense when they cover larger territories regardless of their cell type, retinal location, or developmental stage. These results suggest that a general structural design principle directs the vision-dependent patterning of RGC dendrites.

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

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    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.

  13. Reprogramming amacrine and photoreceptor progenitors into retinal ganglion cells by replacing Neurod1 with Atoh7.

    Science.gov (United States)

    Mao, Chai-An; Cho, Jang-Hyeon; Wang, Jing; Gao, Zhiguang; Pan, Ping; Tsai, Wen-Wei; Frishman, Laura J; Klein, William H

    2013-02-01

    The specification of the seven retinal cell types from a common pool of retina progenitor cells (RPCs) involves complex interactions between the intrinsic program and the environment. The proneural basic helix-loop-helix (bHLH) transcriptional regulators are key components for the intrinsic programming of RPCs and are essential for the formation of the diverse retinal cell types. However, the extent to which an RPC can re-adjust its inherent program and the mechanisms through which the expression of a particular bHLH factor influences RPC fate is unclear. Previously, we have shown that Neurod1 inserted into the Atoh7 locus activates the retinal ganglion cell (RGC) program in Atoh7-expressing RPCs but not in Neurod1-expressing RPCs, suggesting that Atoh7-expressing RPCs are not able to adopt the cell fate determined by Neurod1, but rather are pre-programmed to produce RGCs. Here, we show that Neurod1-expressing RPCs, which are destined to produce amacrine and photoreceptor cells, can be re-programmed into RGCs when Atoh7 is inserted into the Neurod1 locus. These results suggest that Atoh7 acts dominantly to convert a RPC subpopulation not destined for an RGC fate to adopt that fate. Thus, Atoh7-expressing and Neurod1-expressing RPCs are intrinsically different in their behavior. Additionally, ChIP-Seq analysis identified an Atoh7-dependent enhancer within the intronic region of Nrxn3. The enhancer recognized and used Atoh7 in the developing retina to regulate expression of Nrxn3, but could be forced to use Neurod1 when placed in a different regulatory context. The results indicate that Atoh7 and Neurod1 activate distinct sets of genes in vivo, despite their common DNA-binding element.

  14. An AD-related neuroprotector rescues transformed rat retinal ganglion cells from CoCl₂-induced apoptosis.

    Science.gov (United States)

    Men, Jie; Zhang, Xiaohui; Yang, Yang; Gao, Dianwen

    2012-05-01

    Some ocular diseases characterized by apoptotic death of retinal ganglion cells (RGCs) and Alzheimer's disease (AD) are chronic neurodegenerative disorders and have similarities in neuropathology. Humanin (HN) is known for its ability to suppress neuronal death induced by AD-related insults. In present study, we investigated the neuroprotective effects of HN on hypoxia-induced toxicity in RGC-5 cells. Hypoxia mimetic compound cobalt chloride (CoCl₂) could increase the cell viability loss and apoptosis, whereas HN can significantly attenuate these effects. This finding may provide new therapeutics for the retinal neurodegenerative diseases targeting neuroprotection.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

  17. 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

  18. 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.

  19. Retinal nerve fiber layer and ganglion cell complex thickness in patients with type 2 diabetes mellitus

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    Mehmet Demir

    2014-01-01

    Full Text Available Aim: The aim of the following study is to evaluate the retinal nerve fiber layer (RNFL and ganglion cell complex (GCC thickness in patients with type 2 diabetes mellitus (DM. Materials and Methods: Average, inferior, and superior values of RNFL and GCC thickness were measured in 123 patients using spectral domain optical coherence tomography. The values of participants with DM were compared to controls. Diabetic patients were collected in Groups 1, 2 and 3. Group 1 = 33 participants who had no diabetic retinopathy (DR; Group 2 = 30 participants who had mild nonproliferative DR and Group 3 = 30 participants who had moderate non-proliferative DR. The 30 healthy participants collected in Group 4. Analysis of variance test and a multiple linear regression analysis were used for statistical analysis. Results: The values of RNFL and GCC in the type 2 diabetes were thinner than controls, but this difference was not statistically significant. Conclusions: This study showed that there is a nonsignificant loss of RNFL and GCC in patients with type 2 diabetes.

  20. NF-Protocadherin Regulates Retinal Ganglion Cell Axon Behaviour in the Developing Visual System.

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    Louis C Leung

    Full Text Available Cell adhesion molecules play a central role in mediating axonal tract development within the nascent nervous system. NF-protocadherin (NFPC, a member of the non-clustered protocadherin family, has been shown to regulate retinal ganglion cell (RGC axon and dendrite initiation, as well as influencing axonal navigation within the mid-optic tract. However, whether NFPC mediates RGC axonal behaviour at other positions within the optic pathway remains unclear. Here we report that NFPC plays an important role in RGC axonogenesis, but not in intraretinal guidance. Moreover, axons with reduced NFPC levels exhibit insensitivity to Netrin-1, an attractive guidance cue expressed at the optic nerve head. Netrin-1 induces rapid turnover of NFPC localized to RGC growth cones, suggesting that the regulation of NFPC protein levels may underlie Netrin-1-mediated entry of RGC axons into the optic nerve head. At the tectum, we further reveal a function for NFPC in controlling RGC axonal entry into the final target area. Collectively, our results expand our understanding of the role of NFPC in RGC guidance and illustrate that this adhesion molecule contributes to axon behaviour at multiple points in the optic pathway.

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

    Institute of Scientific and Technical Information of China (English)

    Ming-lei Han; Guo-hua Liu; Jin Guo; Shu-juan Yu; Jing Huang

    2016-01-01

    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 (H2O2)-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 H2O2. Western blot assay showed that in H2O2-damaged RGC-5 cells, imipramine activated TrkB pathways through extracellular signal-regulated protein kinase/TrkB phosphorylation. TUNEL staining assay also demonstrated that imipramine ameliorated H2O2-induced apoptosis in RGC-5 cells. Finally, TrkB-IgG intervention was able to reverse the protective effect of imipramine on H2O2-induced RGC-5 apoptosis. Imipramine therefore protects RGCs from oxidative stress-induced apoptosis through the TrkB signaling pathway.

  2. Apigenin prevents TNF-α induced apoptosis of primary rat retinal ganglion cells.

    Science.gov (United States)

    Fu, M-S; Zhu, B-J; Luo, D-W

    2014-11-25

    TNF-α has recently been identified to be a mediator of retinal ganglion cell (RGC) death, while glial cells are relatively protected against this death stimulus. Exposure of RGCs to TNF-α is thought to contribute to RGC apoptosis. Apigenin is a flavone with powerful anti-inflammatory properties that exists naturally in various plants and Chinese medicine. In our study, MTT assays showed that apigenin significantly inhibited the decrease of RGC viability induced by TNF-α in a dose-dependent manner. Pretreatment with apigenin prevented TNF-α-induced apoptosis in a dose-dependent manner as shown by flow cytometry. The production of ATP and the total oxygen uptake were also promoted after apigenin administration. TNF-α stimulation led to a significant reduction of bcl-2 and enhancement of bax, which was reversed by apigenin treatment. Apigenin treatment also alleviated the increased caspase-3 activity induced by TNF-α. Moreover, luciferase reporter assay indicated that apigenin dose-dependently decreased NF-κB activation induced by TNF-α, but had no significant effect on activation of AP-1. Collectively, these data demonstrated that apigenin alleviated TNF-α-induced apoptosis through inhibition of caspase-dependent apoptotic pathway and activation of nuclear factor-kappaB. Therefore, apigenin may be developed as an anti-apoptotic drug to treat retinopathy.

  3. Nerve growth factor protects against palmitic acid-induced injury in retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    Pan-shi Yan; Shu Tang; Hai-feng Zhang; Yuan-yuan Guo; Zhi-wen Zeng; Qiang Wen

    2016-01-01

    Accumulating evidence supports an important role for nerve growth factor (NGF) in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid (PA), a metabolic factor implicated in the development of dia-betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF signiifcantly attenuated the levels of reactive oxygen species (ROS) and malondialde-hyde (MDA) in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 (PI3K inhibitor), Akt VIII inhibitor, and PD98059 (ERK1/2 inhibitor). Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 sig-naling pathways.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Modeling the impact of common noise inputs on the network activity of retinal ganglion cells.

    Science.gov (United States)

    Vidne, Michael; Ahmadian, Yashar; Shlens, Jonathon; Pillow, Jonathan W; Kulkarni, Jayant; Litke, Alan M; Chichilnisky, E J; Simoncelli, Eero; Paninski, Liam

    2012-08-01

    Synchronized spontaneous firing among retinal ganglion cells (RGCs), on timescales faster than visual responses, has been reported in many studies. Two candidate mechanisms of synchronized firing include direct coupling and shared noisy inputs. In neighboring parasol cells of primate retina, which exhibit rapid synchronized firing that has been studied extensively, recent experimental work indicates that direct electrical or synaptic coupling is weak, but shared synaptic input in the absence of modulated stimuli is strong. However, previous modeling efforts have not accounted for this aspect of firing in the parasol cell population. Here we develop a new model that incorporates the effects of common noise, and apply it to analyze the light responses and synchronized firing of a large, densely-sampled network of over 250 simultaneously recorded parasol cells. We use a generalized linear model in which the spike rate in each cell is determined by the linear combination of the spatio-temporally filtered visual input, the temporally filtered prior spikes of that cell, and unobserved sources representing common noise. The model accurately captures the statistical structure of the spike trains and the encoding of the visual stimulus, without the direct coupling assumption present in previous modeling work. Finally, we examined the problem of decoding the visual stimulus from the spike train given the estimated parameters. The common-noise model produces Bayesian decoding performance as accurate as that of a model with direct coupling, but with significantly more robustness to spike timing perturbations.

  6. Differentiation of human ESCs to retinal ganglion cells using a CRISPR engineered reporter cell line.

    Science.gov (United States)

    Sluch, Valentin M; Davis, Chung-ha O; Ranganathan, Vinod; Kerr, Justin M; Krick, Kellin; Martin, Russ; Berlinicke, Cynthia A; Marsh-Armstrong, Nicholas; Diamond, Jeffrey S; Mao, Hai-Quan; Zack, Donald J

    2015-11-13

    Retinal ganglion cell (RGC) injury and cell death from glaucoma and other forms of optic nerve disease is a major cause of irreversible vision loss and blindness. Human pluripotent stem cell (hPSC)-derived RGCs could provide a source of cells for the development of novel therapeutic molecules as well as for potential cell-based therapies. In addition, such cells could provide insights into human RGC development, gene regulation, and neuronal biology. Here, we report a simple, adherent cell culture protocol for differentiation of hPSCs to RGCs using a CRISPR-engineered RGC fluorescent reporter stem cell line. Fluorescence-activated cell sorting of the differentiated cultures yields a highly purified population of cells that express a range of RGC-enriched markers and exhibit morphological and physiological properties typical of RGCs. Additionally, we demonstrate that aligned nanofiber matrices can be used to guide the axonal outgrowth of hPSC-derived RGCs for in vitro optic nerve-like modeling. Lastly, using this protocol we identified forskolin as a potent promoter of RGC differentiation.

  7. Response properties of ON-OFF retinal ganglion cells to high-order stimulus statistics.

    Science.gov (United States)

    Xiao, Lei; Gong, Han-Yan; Gong, Hai-Qing; Liang, Pei-Ji; Zhang, Pu-Ming

    2014-10-17

    The visual stimulus statistics are the fundamental parameters to provide the reference for studying visual coding rules. In this study, the multi-electrode extracellular recording experiments were designed and implemented on bullfrog retinal ganglion cells to explore the neural response properties to the changes in stimulus statistics. The changes in low-order stimulus statistics, such as intensity and contrast, were clearly reflected in the neuronal firing rate. However, it was difficult to distinguish the changes in high-order statistics, such as skewness and kurtosis, only based on the neuronal firing rate. The neuronal temporal filtering and sensitivity characteristics were further analyzed. We observed that the peak-to-peak amplitude of the temporal filter and the neuronal sensitivity, which were obtained from either neuronal ON spikes or OFF spikes, could exhibit significant changes when the high-order stimulus statistics were changed. These results indicate that in the retina, the neuronal response properties may be reliable and powerful in carrying some complex and subtle visual information.

  8. Optic neuritis and retinal ganglion cell loss in a chronic murine model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Thomas eQuinn

    2011-08-01

    Full Text Available Multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE are neurodegenerative diseases with characteristic inflammatory demyelination in the central nervous system, including the optic nerve. Neuronal and axonal damage is considered to be the main cause of long-term disability in patients with MS. Neuronal loss, including retinal ganglion cell (RGC apoptosis in eyes with optic neuritis, also occurs in EAE. However, there is significant variability in the clinical course and level of neuronal damage in MS and EAE. The current studies examine the mechanisms and kinetics of RGC loss in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein to induce a chronic EAE disease. Clinical progression of EAE was scored daily and vision was assessed by optokinetic responses. At various time points, RGCs were counted and optic nerves were examined for inflammatory cell infiltration. Almost all EAE mice develop optic neuritis by day 15 post-immunization; however, RGC loss is delayed in these mice. No RGC loss is detected 25 days post-immunization, whereas RGC numbers in EAE mice significantly and progressively decrease compared to controls from 35-50 days post-immunization. The delayed time course of RGC loss is in stark contrast to that reported in relapsing EAE, as well as in rats with chronic EAE. Results suggest that different clinical disease courses of optic nerve inflammation may trigger distinct mechanisms of neuronal damage, or RGCs in different rodent strains may have variable resistance to neuronal degeneration.

  9. Roles of PACAP-containing retinal ganglion cells in circadian timing.

    Science.gov (United States)

    Hannibal, Jens

    2006-01-01

    The brain's biological clock located in the suprachiasmatic nucleus (SCN) generates circadian rhythms in physiology and behavior. The clock-driven rhythms need daily adjustment (entrainment) to be synchronized with the astronomical day of 24 h. The most important stimulus for entrainment of the clock is the light-dark (LD) cycle. In this review functional elements of the light entrainment pathway will be considered with special focus on the neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP), which is found exclusively in the monosynaptic neuronal pathway mediating light information to the SCN, the retinohypothalamic tract (RHT). The retinal ganglion cells of the RHT are intrinsically photosensitive due to the expression of melanopsin and seem to constitute a non-image forming photosensitive system in the mammalian eye regulating circadian timing, masking behavior, light-regulated melatonin secretion, and the pupillary light reflex. Evidence from in vitro and in vivo studies and studies of mice lacking PACAP and the specific PACAP receptor (PAC1) indicate that PACAP and glutamate are neurotransmitters in the RHT which in a clock and concentration-dependent manner interact during light entrainment of the clock.

  10. 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...

  11. Protective effects of triptolide on retinal ganglion cells in a rat model of chronic glaucoma

    Directory of Open Access Journals (Sweden)

    Yang F

    2015-11-01

    Full Text Available Fan Yang, Dongmei Wang, Lingling Wu, Ying Li Ophthalmology Department, Peking University Third Hospital, Beijing, People’s Republic of China Purpose: To study the effects of triptolide, a Chinese herb extract, on retinal ganglion cells (RGCs in a rat model of chronic glaucoma.Methods: Eighty Wistar rats were randomly divided into triptolide group (n=40 and normal saline (NS group (n=40. Angle photocoagulation was used to establish the model of glaucoma, with right eye as laser treated eye and left eye as control eye. Triptolide group received triptolide intraperitoneally daily, while NS group received NS. Intraocular pressure (IOP, anti-CD11b immunofluorescent stain in retina and optic nerve, RGCs count with Nissel stain and microglia count with anti-CD11b immunofluorescence stain in retina flat mounts, retinal tumor necrosis factor (TNF-α mRNA detection by reverse transcription–polymerase chain reaction, and double immunofluorescent labeling with anti-TNF-α and anti-CD11b in retinal frozen section were performed.Results: Mean IOP of the laser treated eyes significantly increased 3 weeks after photocoagulation (P<0.05, with no statistical difference between the two groups (P>0.05. RGCs survival in the laser treated eyes was significantly improved in the triptolide group than the NS group (P<0.05. Microglia count in superficial retina of the laser treated eyes was significantly less in the triptolide group (30.40±4.90 than the NS group (35.06±7.59 (P<0.05. TNF-α mRNA expression in the retina of the laser treated eyes in the triptolide group decreased by 60% compared with that in the NS group (P<0.01. The double immunofluorescent labeling showed that TNF-α was mainly distributed around the microglia.Conclusion: Triptolide improved RGCs survival in this rat model of chronic glaucoma, which did not depend on IOP decrease but might be exerted by inhibiting microglia activities and reducing TNF-α secretion. Keywords: glaucoma, triptolide

  12. Genome-wide association and linkage analyses localize a progressive retinal atrophy locus in Persian cats.

    Science.gov (United States)

    Alhaddad, Hasan; Gandolfi, Barbara; Grahn, Robert A; Rah, Hyung-Chul; Peterson, Carlyn B; Maggs, David J; Good, Kathryn L; Pedersen, Niels C; Lyons, Leslie A

    2014-08-01

    Hereditary eye diseases of animals serve as excellent models of human ocular disorders and assist in the development of gene and drug therapies for inherited forms of blindness. Several primary hereditary eye conditions affecting various ocular tissues and having different rates of progression have been documented in domestic cats. Gene therapy for canine retinopathies has been successful, thus the cat could be a gene therapy candidate for other forms of retinal degenerations. The current study investigates a hereditary, autosomal recessive, retinal degeneration specific to Persian cats. A multi-generational pedigree segregating for this progressive retinal atrophy was genotyped using a 63 K SNP array and analyzed via genome-wide linkage and association methods. A multi-point parametric linkage analysis localized the blindness phenotype to a ~1.75 Mb region with significant LOD scores (Z ≈ 14, θ = 0.00) on cat chromosome E1. Genome-wide TDT, sib-TDT, and case-control analyses also consistently supported significant association within the same region on chromosome E1, which is homologous to human chromosome 17. Using haplotype analysis, a ~1.3 Mb region was identified as highly associated for progressive retinal atrophy in Persian cats. Several candidate genes within the region are reasonable candidates as a potential causative gene and should be considered for molecular analyses.

  13. Electrophysiological characterization of nicotinic acetylcholine receptors in cat petrosal ganglion neurons in culture: effects of cytisine and its bromo derivatives.

    Science.gov (United States)

    Varas, Rodrigo; Valdés, Viviana; Iturriaga-Vásquez, Patricio; Cassels, Bruce K; Iturriaga, Rodrigo; Alcayaga, Julio

    2006-02-09

    Petrosal ganglion neurons are depolarized and fire action potentials in response to acetylcholine and nicotine. However, little is known about the subtype(s) of nicotinic acetylcholine receptors involved, although alpha4 and alpha7 subunits have been identified in petrosal ganglion neurons. Cytisine, an alkaloid unrelated to nicotine, and its bromo derivatives are agonists exhibiting different affinities, potencies and efficacies at nicotinic acetylcholine receptors containing alpha4 or alpha7 subunits. To characterize the receptors involved, we studied the effects of these agonists and the nicotinic acetylcholine receptor antagonists hexamethonium and alpha-bungarotoxin in isolated petrosal ganglion neurons. Petrosal ganglia were excised from anesthetized cats and cultured for up to 16 days. Using patch-clamp technique, we recorded whole-cell currents evoked by 5-10 s applications of acetylcholine, cytisine or its bromo derivatives. Agonists and antagonists were applied by gravity from a pipette near the neuron surface. Neurons responded to acetylcholine, cytisine, 3-bromocytisine and 5-bromocytisine with fast inward currents that desensitized during application of the stimuli and were reversibly blocked by 1 microM hexamethonium or 10 nM alpha-bungarotoxin. The order of potency of the agonists was 3-bromocytisine > acetylcholine approximately = cytisine > 5-bromocytisine, suggesting that homomeric alpha7 neuronal nicotinic receptors predominate in cat petrosal ganglion neurons in culture.

  14. Electroacupuncture upregulated platelet derived growth factor expression in spared dorsal root ganglion of cats

    Institute of Scientific and Technical Information of China (English)

    Xifeng Wang; Lianshuang Zhang; Xiaobo Xu; Wei Zhao; Guixiang Liu

    2012-01-01

    A bilateral spared dorsal root ganglion model was established in healthy adult cats by bilateral resection of L1-5 and L7-S2 dorsal root ganglia. L6 dorsal root ganglia were spared. Zusanli (ST36) and Xuanzhong (BL39) or Futu (ST32) and Sanyinjiao (SP6) were alternatively electro-stimulated on the right leg. Immunohistochemical staining of anti-serum platelet-derived growth factor demonstrated that the number of total neurons and medium-small sized platelet-derived growth factor positive neurons was significantly decreased on the 7th day following injury. After 7 days of acupuncture, the total number of positive and large neurons staining for platelet-derived growth factor on the acupuncture side significantly increased compared to the non-acupuncture side. After acupuncture for 14 days, the total positive and medium-small sized neurons significantly increased compared with the non-acupuncture side. Results indicate that acupuncture promoted the synthesis of platelet-derived growth factor in spared dorsal root ganglia.

  15. Astaxanthin Attenuates the Apoptosis of Retinal Ganglion Cells in db/db Mice by Inhibition of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Xiao-Li Kang

    2013-03-01

    Full Text Available Diabetic retinopathy is a common diabetic eye disease caused by changes in retinal ganglion cells (RGCs. It is an ocular manifestation of systemic disease, which affects up to 80% of all patients who have had diabetes for 10 years or more. The genetically diabetic db/db mouse, as a model of type-2 diabetes, shows diabetic retinopathy induced by apoptosis of RGCs. Astaxanthin is a carotenoid with powerful antioxidant properties that exists naturally in various plants, algae and seafood. Here, astaxanthin was shown to reduce the apoptosis of RGCs and improve the levels of oxidative stress markers, including superoxide anion, malondialdehyde (MDA, a marker of lipid peroxidation, 8-hydroxy-2-deoxyguanosine (8-OHdG, indicator of oxidative DNA damage and MnSOD (manganese superoxide dismutase activity in the retinal tissue of db/db mouse. In addition, astaxanthin attenuated hydrogen peroxide(H2O2-induced apoptosis in the transformed rat retinal ganglion cell line RGC-5. Therefore, astaxanthin may be developed as an antioxidant drug to treat diabetic retinopathy.

  16. 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.

  17. Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells.

    Science.gov (United States)

    Zhao, Xiwu; Reifler, Aaron N; Schroeder, Melanie M; Jaeckel, Elizabeth R; Chervenak, Andrew P; Wong, Kwoon Y

    2017-03-06

    Retinal neurons use sustained and transient light responses to encode visual stimuli of different frequency ranges, but the underlying mechanisms remain poorly understood. In particular, although earlier studies in retinal ganglion cells (RGCs) proposed seven potential mechanisms, all seven have since been disputed, and it remains unknown whether different RGC types use different mechanisms or how many mechanisms are used by each type. Here, we conduct a comprehensive survey in mice and rats of 12 candidate mechanisms that could conceivably produce tonic rod/cone-driven ON responses in intrinsically photosensitive RGCs (ipRGCs) and transient ON responses in three types of direction-selective RGCs (TRHR+, Hoxd10+ ON, and Hoxd10+ ON-OFF cells). We find that the tonic kinetics of ipRGCs arises from their substantially above-threshold resting potentials, input from sustained ON bipolar cells, absence of amacrine cell inhibition of presynaptic ON bipolar cells, and mGluR7-mediated maintenance of light-evoked glutamatergic input. All three types of direction-selective RGCs receive input from transient ON bipolar cells, and each type uses additional strategies to promote photoresponse transience: presynaptic inhibition and dopaminergic modulation for TRHR+ cells, center/surround antagonism and relatively negative resting potentials for Hoxd10+ ON cells, and presynaptic inhibition for Hoxd10+ ON-OFF cells. We find that the sustained nature of ipRGCs' rod/cone-driven responses depends neither on melanopsin nor on N-methyl-d-aspartate (NMDA) receptors, whereas the transience of the direction-selective cells' responses is influenced neither by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor desensitization nor by glutamate uptake. For all cells, we further rule out spike frequency adaptation and intracellular Ca(2+) as determinants of photoresponse kinetics. In conclusion, different RGC types use diverse mechanisms to produce sustained or

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

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    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.

  19. Quantitative measurement of retinal ganglion cell populations via histology-based random forest classification.

    Science.gov (United States)

    Hedberg-Buenz, Adam; Christopher, Mark A; Lewis, Carly J; Fernandes, Kimberly A; Dutca, Laura M; Wang, Kai; Scheetz, Todd E; Abràmoff, Michael D; Libby, Richard T; Garvin, Mona K; Anderson, Michael G

    2016-05-01

    The inner surface of the retina contains a complex mixture of neurons, glia, and vasculature, including retinal ganglion cells (RGCs), the final output neurons of the retina and primary neurons that are damaged in several blinding diseases. The goal of the current work was two-fold: to assess the feasibility of using computer-assisted detection of nuclei and random forest classification to automate the quantification of RGCs in hematoxylin/eosin (H&E)-stained retinal whole-mounts; and if possible, to use the approach to examine how nuclear size influences disease susceptibility among RGC populations. To achieve this, data from RetFM-J, a semi-automated ImageJ-based module that detects, counts, and collects quantitative data on nuclei of H&E-stained whole-mounted retinas, were used in conjunction with a manually curated set of images to train a random forest classifier. To test performance, computer-derived outputs were compared to previously published features of several well-characterized mouse models of ophthalmic disease and their controls: normal C57BL/6J mice; Jun-sufficient and Jun-deficient mice subjected to controlled optic nerve crush (CONC); and DBA/2J mice with naturally occurring glaucoma. The result of these efforts was development of RetFM-Class, a command-line-based tool that uses data output from RetFM-J to perform random forest classification of cell type. Comparative testing revealed that manual and automated classifications by RetFM-Class correlated well, with 83.2% classification accuracy for RGCs. Automated characterization of C57BL/6J retinas predicted 54,642 RGCs per normal retina, and identified a 48.3% Jun-dependent loss of cells at 35 days post CONC and a 71.2% loss of RGCs among 16-month-old DBA/2J mice with glaucoma. Output from automated analyses was used to compare nuclear area among large numbers of RGCs from DBA/2J mice (n = 127,361). In aged DBA/2J mice with glaucoma, RetFM-Class detected a decrease in median and mean nucleus size

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

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    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.

  1. 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.

  2. Transcorneal electrical stimulation alters morphology and survival of retinal ganglion cells after optic nerve damage.

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    Henrich-Noack, Petra; Voigt, Nadine; Prilloff, Sylvia; Fedorov, Anton; Sabel, Bernhard A

    2013-05-24

    Traumatic optic nerve injury leads to retrograde death of retinal ganglion cells (RGCs), but transcorneal electrical stimulation (TES) can increase the cell survival rate. To understand the mechanisms and to further define the TES-induced effects we monitored in living animals RGC morphology and survival after optic nerve crush (ONC) in real time by using in vivo confocal neuroimaging (ICON) of the retina. ONC was performed in rats and ICON was performed before crush and on post-lesion days 3, 7 and 15 which allowed us to repeatedly record RGC number and size. TES or sham-stimulation were performed immediately after the crush and on post-injury day 11. Three days after ONC we detected a higher percentage of surviving RGCs in the TES group as compared to sham-treated controls. However, the difference was below significance level on day 7 and disappeared completely by day 15. The death rate was more variable amongst the TES-treated rats than in the control group. Morphological analysis revealed that average cell size changed significantly in the control group but not in stimulated animals and the morphological alterations of surviving neurons were smaller in TES-treated compared to control cells. In conclusion, TES delays post-traumatic cell death significantly. Moreover, we found "responder animals" which also benefited in the long-term from the treatment. Our in vivo cellular imaging results provide evidence that TES reduces ONC-associated neuronal swelling and shrinkage especially in RGCs which survived long-term. Further studies are now needed to determine the differences of responders vs. non-responders.

  3. α-Lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction.

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    Inman, Denise M; Lambert, Wendi S; Calkins, David J; Horner, Philip J

    2013-01-01

    Oxidative stress has been implicated in neurodegenerative diseases, including glaucoma. However, due to the lack of clinically relevant models and expense of long-term testing, few studies have modeled antioxidant therapy for prevention of neurodegeneration. We investigated the contribution of oxidative stress to the pathogenesis of glaucoma in the DBA/2J mouse model of glaucoma. Similar to other neurodegenerative diseases, we observed lipid peroxidation and upregulation of oxidative stress-related mRNA and protein in DBA/2J retina. To test the role of oxidative stress in disease progression, we chose to deliver the naturally occurring, antioxidant α-lipoic acid (ALA) to DBA/2J mice in their diet. We used two paradigms for ALA delivery: an intervention paradigm in which DBA/2J mice at 6 months of age received ALA in order to intervene in glaucoma development, and a prevention paradigm in which DBA/2J mice were raised on a diet supplemented with ALA, with the goal of preventing glaucoma development. At 10 and 12 months of age (after 4 and 11 months of dietary ALA respectively), we measured changes in genes and proteins related to oxidative stress, retinal ganglion cell (RGC) number, axon transport, and axon number and integrity. Both ALA treatment paradigms showed increased antioxidant gene and protein expression, increased protection of RGCs and improved retrograde transport compared to control. Measures of lipid peroxidation, protein nitrosylation, and DNA oxidation in retina verified decreased oxidative stress in the prevention and intervention paradigms. These data demonstrate the utility of dietary therapy for reducing oxidative stress and improving RGC survival in glaucoma.

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

    Science.gov (United States)

    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.

  5. 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.

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

    Science.gov (United States)

    Purrier, Nicole; Engeland, William C; Kofuji, Paulo

    2014-01-01

    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.

  7. Erythropoietin (EPO) protects against high glucose-induced apoptosis in retinal ganglional cells.

    Science.gov (United States)

    Wang, Yunxiao; Zhang, Hui; Liu, Yanping; Li, Ping; Cao, Zhihong; Cao, Yu

    2015-03-01

    The aim of this study was to investigate the protective effect and mechanism of EPO on the apoptosis induced by high levels of glucose in retinal ganglial cells (RGCs). High glucose-induced apoptosis model was established in RGCs isolated from SD rats (1-3 days old) and identified with Thy1.1 mAb and MAP-2 pAb. The apoptosis was determined by Hochest assay. The levels of ROS were quantitated by staining the cells with dichloro-dihydro-fluorescein diacetate (DCFH-DA) and measure by flow cytometry. The SOD, GSH-Px, CAT activities, and levels of T-AOC and MDA were determined by ELISA. Change in mitochondrial membrane potential (Δψm) was also assessed by flow cytometry, and expressions of Bcl-2, Bax, caspase-3, caspase-9, and cytochrome C were assessed by western blotting. The RGCs treated with high glucose levels exhibited significantly increased apoptotic rate and concentrations of ROS and MDA. Pretreatment of the cells with EPO caused a significant blockade of the high glucose-induced increase in ROS and MDA levels and apoptotic rate. EPO also increased the activities of SOD, GSH-Px, and CAT, and recovered the levels of T-AOC levels. As a consequence, the mitochondrial membrane potential was improved and Cyt c release into the cytoplasm was prevented which led to significantly suppressed up-regulation of Bax reducing the Bax/Bcl-2 ratio. The expressions of caspase-3 and caspase-9 induced by high glucose exposure were also ameliorated in the RGCs treated with EPO. The protective effect of EPO against apoptosis was mediated through its antioxidant action. Thus, it blocked the generation of pro-apoptotic proteins and apoptotic degeneration of the RGCs by preventing the mitochondrial damage.

  8. Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma

    Science.gov (United States)

    Schori, Hadas; Kipnis, Jonathan; Yoles, Eti; Woldemussie, Elizabeth; Ruiz, Guadalupe; Wheeler, Larry A.; Schwartz, Michal

    2001-03-01

    Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 ± 270 and 1,329 ± 121, respectively, mean ± SEM; P myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8%±6.8% to 4.3%±1.6%, without affecting the intraocular pressure. This study may point the way to a therapy for glaucoma, a neurodegenerative disease of the optic nerve often associated with increased intraocular pressure, as well as for acute and chronic degenerative disorders in which glutamate is a prominent participant.

  9. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Marianna Foldvari; Ding Wen Chen

    2016-01-01

    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 sufifcient 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 dis-cuss the challenges currently being faced in RGC-related therapy development with special considerations to the existence of multiple RGC subtypes and the lack of efifcient and representativein vitro models for rapid and reliable screening in the drug development process.

  11. 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.

  12. Developmental maturation of passive electrical properties in retinal ganglion cells of rainbow trout.

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    Picones, Arturo; Chung, S Clare; Korenbrot, Juan I

    2003-04-01

    We investigated the electrotonic and anatomical features of the dendritic arbor in developing retinal ganglion cells (RGCs). Cell anatomy was studied by filling individual cells with fluorescent, membrane-bound dyes and using computer-assisted image reconstruction. Electrotonic properties were characterized through an analysis of charging membrane currents measured with tight-seal electrodes in the whole-cell mode. We studied developing RGCs in the peripheral growth zone (PGZ) of a fish retina. The PGZ presents a developmental time-line ranging from pluripotent, proliferating cells at the extreme edge, to mature, fully developed retina more centrally. In the PGZ, RGCs mature through three histologically distinct zones (in developmental sequence): bulge, transition and mature zones. In the most peripheral three-quarters of the bulge zone, cells have rounded somas, lack dendritic extensions and some are coupled so that membrane-bound dyes traverse from one cell to its immediate neighbours. In the more central quarter of the bulge, cells' dendrites are few, short and of limited branching. In the transition zone dendritic arbors becomes progressively more expansive and branched and we present a morphometric analysis of these changes. Regardless of the size and branching pattern of the developing RGC dendritic arbor, the ratio of the diameters of parent and progeny dendrites at any branching nodes is well described by Rall's 3/2 power law. Given this anatomical feature, the RGC passive electrical properties are well described by an equivalent electrical circuit consisting of an isopotential cell body in parallel with a single equivalent cylinder of finite length. We measured the values of the electrical parameters that define this equivalent circuit in bulge, transition and mature RGCs. As RGCs develop the electrical properties of their dendritic arbor change in an orderly and tightly regulated manner, not randomly. Electrically, dendritic arbors develop along either of

  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

    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

  14. 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.

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    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.

  15. Impact of morphometry, myelinization and synaptic current strength on spike conduction in human and cat spiral ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Frank Rattay

    Full Text Available BACKGROUND: Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. METHODOLOGY/PRINCIPAL FINDINGS: Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA synaptic stimuli. CONCLUSIONS/SIGNIFICANCE: Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Both electrical stimulation thresholds and SMI-32-immunoreactive retinal ganglion cell density correlate with age in S334ter line 3 rat retina.

    Science.gov (United States)

    Chan, Leanne L H; Lee, Eun-Jin; Humayun, Mark S; Weiland, James D

    2011-06-01

    Electrical stimulation threshold and retinal ganglion cell density were measured in a rat model of retinal degeneration. We performed in vivo electrophysiology and morphometric analysis on normal and S334ter line 3 (RD) rats (ages 84-782 days). We stimulated the retina in anesthetized animals and recorded evoked responses in the superior colliculus. Current pulses were delivered with a platinum-iridium (Pt-Ir) electrode of 75-μm diameter positioned on the epiretinal surface. In the same animals used for electrophysiology, SMI-32 immunolabeling of the retina enabled ganglion cell counting. An increase in threshold currents positively correlated with age of RD rats. SMI-32-labeled retinal ganglion cell density negatively correlated with age of RD rats. ANOVA shows that RD postnatal day (P)100 and P300 rats have threshold and density similar to normal rats, but RD P500 and P700 rats have threshold and density statistically different from normal rats (P < 0.05). Threshold charge densities were within the safety limits of Pt for all groups and pulse configurations, except at RD P600 and RD P700, where pulses were only safe up to 1- and 0.2-ms duration, respectively. Preservation of ganglion cells may enhance the efficiency and safety of electronic retinal implants.

  18. Characteristics of retinal reflectance changes induced by transcorneal electrical stimulation in cat eyes.

    Directory of Open Access Journals (Sweden)

    Takeshi Morimoto

    Full Text Available Transcorneal electrical stimulation (TES activates retinal neurons leading to visual sensations. How the retinal cells are activated by TES has not been definitively determined. Investigating the reflectance changes of the retina is an established technique and has been used to determine the mechanism of retinal activation. The purpose of this study was to evaluate the reflectance changes elicited by TES in cat eyes. Eight eyes of Eight cats were studied under general anesthesia. Biphasic electrical pulses were delivered transcornealy. The fundus images observed with near-infrared light (800-880 nm were recorded every 25 ms for 26 s. To improve the signal-to-noise ratio, the images of 10 consecutive recordings were averaged. Two-dimensional topographic maps of the reflective changes were constructed by subtracting images before from those after the TES. The effects of different stimulus parameters, e.g., current intensity, pulse duration, frequency, and stimulus duration, on the reflective changes were studied. Our results showed that after TES, the reflective changes appeared on the retinal vessels and optic disc. The intensity of reflectance changes increased as the current intensity, pulse duration, and stimulation duration increased (P<0.05 for all. The maximum intensity of the reflective change was obtained when the stimulus frequency was 20 Hz. The time course of the reflectance changes was also altered by the stimulation parameters. The response started earlier and returned to the baseline later with higher current intensities, longer pulse durations, but the time of the peak of the response was not changed. These results showed that the reflective changes were due to the activation of retinal neurons by TES and might involve the vascular changes induced by an activation of the retinal neurons.

  19. Frequency-dependent reduction of voltage-gated sodium current modulates retinal ganglion cell response rate to electrical stimulation

    Science.gov (United States)

    Tsai, David; Morley, John W.; Suaning, Gregg J.; Lovell, Nigel H.

    2011-10-01

    The ability to elicit visual percepts through electrical stimulation of the retina has prompted numerous investigations examining the feasibility of restoring sight to the blind with retinal implants. The therapeutic efficacy of these devices will be strongly influenced by their ability to elicit neural responses that approximate those of normal vision. Retinal ganglion cells (RGCs) can fire spikes at frequencies greater than 200 Hz when driven by light. However, several studies using isolated retinas have found a decline in RGC spiking response rate when these cells were stimulated at greater than 50 Hz. It is possible that the mechanism responsible for this decline also contributes to the frequency-dependent 'fading' of electrically evoked percepts recently reported in human patients. Using whole-cell patch clamp recordings of rabbit RGCs, we investigated the causes for the spiking response depression during direct subretinal stimulation of these cells at 50-200 Hz. The response depression was not caused by inhibition arising from the retinal network but, instead, by a stimulus-frequency-dependent decline of RGC voltage-gated sodium current. Under identical experimental conditions, however, RGCs were able to spike at high frequency when driven by light stimuli and intracellular depolarization. Based on these observations, we demonstrated a technique to prevent the spiking response depression.

  20. Heat Shock Protein 72 Protects Retinal Ganglion Cells in Rat Model of Acute Glaucoma

    Institute of Scientific and Technical Information of China (English)

    Guoping Qing; Xuanchu Duan; Youqin Jiang

    2005-01-01

    Purpose: To investigate whether the induction of heat shock protein (HSP)72 by heat stress (HS) or zinc (Zn2+ ) administration can increase survival of retinal ganglion cells (RGC) in rat model of acute experimental glaucoma.Methods: Acute glaucoma model was made by intracameral irrigation with BSS at 102 mmHg for two hours in right eyes of male Wistar rats. Glaucoma model rats were treated with HS once a week (six rats) or intraperitoneal injection of zinc sulfate (24.6 mg/kg) every two weeks (six rats), and were referred to as HS group and zinc group, respectively. Untreated model rats served as damage group (six rats). In control groups, quercetin (400 mg/kg) was intraperitoneally injected to inhibit the induction of heat shock proteins 6 hours before HS or zinc administration, and were referred to as HS+que group (six rats) and zinc+que group (six rats), respectively. Subsequent to 16 days of IOP elevation, the rats were sacrificed. Eyes were quickly enucleated, and the retinas were dissected. RGC were labeled with Nissl staining and counted under microscope.Results: The average RGC density in normal Wistar rats was (2504±181) cells/mm2. In damage group, it decreased to (2015±111 ) cells/mm2. The RGC densities at 1,2, and 3 mm from the center of the optic nerve head were (2716±215), (2496±168), and (2317±171) cells/mm2, respectively, for normal rats and (2211±133), (1969±154),and (1872±68) cells/mm2, respectively, for damage group. The latter was significantly lower at all locations compared with the former (P=0.027 for each, Mann-Whitney test).The average RGC densities were (2207±200) cells/mm2 for HS group, (2272±155) cells/mm2 for zinc group, (1964±188) cells/mm2 for HS+que group, (2051 ±214) cells/mm2 for zinc+que group and (2015±111 ) cells/mm2 for damage group. There were significant differences in density of labeled RGCs among the five groups (P=0.040,Kruskal-Wallis test). Both HS and zinc group had higher RGC densities than damage group (P

  1. Targeted knockdown of Cerkl, a retinal dystrophy gene, causes mild affectation of the retinal ganglion cell layer

    NARCIS (Netherlands)

    Garanto, A.; Vicente-Tejedor, J.; Riera, M.; Villa, P. de la; Gonzalez-Duarte, R.; Blanco, R.; Marfany, G.

    2012-01-01

    In order to approach the function of the retinal dystrophy CERKL gene we generated a novel knockout mouse model by cre-mediated targeted deletion of the Cerkl first exon and proximal promoter. The excised genomic region (2.3kb) encompassed the first Cerkl exon, upstream sequences including the proxi

  2. In vivo evaluation of an episcleral multielectrode array for stimulation of the retina with reduced retinal ganglion cell mass.

    Science.gov (United States)

    Siu, Timothy L; Morley, John W

    2008-05-01

    A visual prosthesis is an experimental device designed to activate residual functional neurons in the visual pathway to generate artificial vision for blind patients. Specifically, for photoreceptor disease, a microelectrode array applied to the surface of the sclera could potentially serve to stimulate the remaining interneurons in the retina to produce topographically mapped visual percepts. However, of those neurons spared in the disease process, the retinal ganglion cells (RGC), which represent the final output neurons of the retina, can be markedly reduced in number. Using an albino rabbit model with RGC deficits, acute recording of cortical electrical evoked potential was performed to ascertain whether such a stimulation strategy is feasible. By analyzing the strength-duration curve (current threshold vs. pulse duration) and cortical activation profiles, our results prove that bioelectrically safe and spatially differentiated stimulation of the retina is feasible notwithstanding the condition of markedly reduced RGC counts.

  3. Transient Expression of Fez Family Zinc Finger 2 Protein Regulates the Brn3b Gene in Developing Retinal Ganglion Cells.

    Science.gov (United States)

    Qu, Chunsheng; Bian, Dandan; Li, Xue; Xiao, Jian; Wu, Chunping; Li, Yue; Jiang, Tian; Zhou, Xiangtian; Qu, Jia; Chen, Jie-Guang

    2016-04-01

    Retinal ganglion cells (RGCs) are projection neurons in the neural retina that relay visual information from the environment to the central nervous system. The early expression of MATH5 endows the post-mitotic precursors with RGC competence and leads to the activation ofBrn3bthat marks committed RGCs. Nevertheless, this fate commitment process and, specifically, regulation ofBrn3bremain elusive. To explore the molecular mechanisms underlying RGC generation in the mouse retina, we analyzed the expression and function of Fez family zinc finger 2 (FEZF2), a transcription factor critical for the development of projection neurons in the cerebral cortex.Fezf2mRNA and protein were transiently expressed at embryonic day 16.5 in the inner neuroblast layer and the prospective ganglion cell layer of the retina, respectively. Knockout ofFezf2in the developing retina reduced BRN3B+ cells and increased apoptotic cell markers.Fezf2knockdown by retinalin uteroelectroporation diminished BRN3B but not the coexpressed ISLET1 and BRN3A, indicating that the BRN3B decrease was the cause, not the result, of the overall reduction of BRN3B+ RGCs in theFezf2knockout retina. Moreover, the mRNA and promoter activity ofBrn3bwere increasedin vitroby FEZF2, which bound to a 5' regulatory fragment in theBrn3bgenomic locus. These results indicate that transient expression ofFezf2in the retina modulates the transcription ofBrn3band the survival of RGCs. This study improves our understanding of the transcriptional cascade required for the specification of RGCs and provides novel insights into the molecular basis of retinal development.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Involvement of two different mechanisms in trigeminal ganglion-evoked vasodilatation in the cat lower lip: role of experimental conditions.

    Science.gov (United States)

    Date, H; Kato, M; Izumi, H

    2000-03-15

    The present study was designed to examine the vasodilator mechanisms elicited by electrical stimulation of trigeminal ganglion (TG) in cat lower lip of the cats. When vago-sympathectomized cats were fixed into a stereotaxic frame by means of ear-bars, etc., the lip blood flow (LBF) increase evoked by lingual nerve (LN) stimulation (parasympathetic reflex response) was almost abolished in 15 out of 34 animals, but unaffected in the other 19. With the animal in the stereotaxic frame, electrical stimulation at sites within the TG evoked an LBF increase whether or not the LN stimulation-induced reflex response was intact. However, hexamethonium abolished the TG stimulation-induced LBF increase in animals whose brainstem parasympathetic reflex was intact, but reduced it by only 50% in animals whose reflex was impaired. This difference was seen in all experiments in which the electrode site was within the TG proper, regardless of its exact position. Although the underlying mechanism is unclear, these data suggest that when the TG is stimulated the LBF increase is entirely mediated via the parasympathetic reflex mechanism in animals whose brainstem reflex is intact, and that an antidromic vasodilatation occurs only in animals whose brainstem parasympathetic reflex is impaired.

  6. Suppression of outward K⁺ currents by WIN55212-2 in rat retinal ganglion cells is independent of CB1/CB2 receptors.

    Science.gov (United States)

    Zhang, C-Q; Wu, H-J; Wang, S-Y; Yin, S; Lu, X-J; Miao, Y; Wang, X-H; Yang, X-L; Wang, Z

    2013-12-03

    Cannabinoid CB1 receptor (CB1R) signaling system is extensively distributed in the vertebrate retina. Activation of CB1Rs regulates a variety of functions of retinal neurons through modulating different ion channels. In the present work we studied effects of this receptor signaling on K(+) channels in retinal ganglion cells by patch-clamp techniques. The CB1R agonist WIN55212-2 (WIN) suppressed outward K(+) currents in acutely isolated rat retinal ganglion cells in a dose-dependent manner, with an IC50 of 4.7 μM. We further showed that WIN mainly suppressed the tetraethylammonium (TEA)-sensitive K(+) current component. While CB1Rs were expressed in rat retinal ganglion cells, the WIN effect on K(+) currents was not blocked by either AM251/SR141716, specific CB1R antagonists, or AM630, a selective CB2R antagonist. Consistently, cAMP-protein kinase A (PKA) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways were unlikely involved in the WIN-induced suppression of the K(+) currents because both PKA inhibitors H-89/Rp-cAMP and MAPK/ERK1/2 inhibitor U0126 failed to block the WIN effects. WIN-induced suppression of the K(+) currents was not observed when WIN was intracellularly applied. Furthermore, an endogenous ligand of the cannabinoid receptor anandamide, the specific CB1R agonist ACEA and the selective CB2R agonist CB65 also suppressed the K(+) currents, and the effects were not blocked by AM251/SR141716 or AM630 respectively. All these results suggest that the WIN-induced suppression of the outward K(+) currents in rat retinal ganglion cells, thereby regulating the cell excitability, were not through CB1R/CB2R signaling pathways.

  7. 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

    ). The ipRGCs regulate other nonimage-forming visual functions such as the pupillary light reflex, masking behavior, and light-induced melatonin suppression. To evaluate whether PACAP-immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we......-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...... including the pregeniculate nucleus, the pretectal olivary nucleus, the nucleus of the optic tract, the brachium of the superior colliculus, and the superior colliculus. In conclusion, PACAP-immunoreactive projections with colocalized CtB represent retinal projections of ipRGCs in the macaque monkey...

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

    Science.gov (United States)

    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

  9. No influence of acute RF exposure (GSM-900, GSM-1800, and UMTS) on mouse retinal ganglion cell responses under constant temperature conditions.

    Science.gov (United States)

    Ahlers, Malte T; Ammermüller, Josef

    2014-01-01

    Possible non-thermal effects of radio frequency electromagnetic fields (RF-EMF) on retinal ganglion cells were studied in vitro under conditions of constant temperature. Isolated mouse retinae were exposed to GSM-900, GSM-1800, and universal mobile telecommunication system (UMTS) RF-EMF applying specific absorption rates (SAR) of 0 (sham), 0.02, 0.2, 2, and 20 W/kg. Temperature was kept constant within ±0.5 to 1 °C for GSM-900 and ±0.5 °C for GSM-1800 and UMTS. Responses of retinal ganglion cells to light stimuli of three intensities (0.5, 16, and 445 lx) were recorded before, during, and up to 35 min after exposure. Experiments were performed under double-blind conditions. Changes in light responses during and after exposure were determined for each condition (RF-EMF; SAR value; light intensity) with respect to the responses before exposure, respectively. Changes were calculated using the Euclidian distance of the n-dimensional response vectors, respectively. Some changes already occurred during sham (0 W/kg) exposure, reflecting the intrinsic variability in retinal ganglion cell responses. Comparison of the distance values from sham exposure with those from actual exposure yielded no significant differences. In addition, linear regression analysis of the distance values versus SAR values yielded no consistent dependence of light response changes. From these results we conclude that RF-EMF exposure at three mobile phone frequencies (GSM-900, GSM-1800, UMTS) and SARs up to 20 W/kg has no acute effects on retinal ganglion cell responses under constant temperature conditions.

  10. Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Complex in Patients with Optic Neuritis or Neuromyelitis Optica Spectrum Disorders Using Optical Coherence Tomography in a Chinese Cohort

    OpenAIRE

    Guohong Tian; Zhenxin Li; Guixian Zhao; Chaoyi Feng; Mengwei Li; Yongheng Huang; Xinghuai Sun

    2015-01-01

    We evaluate a cohort of optic neuritis and neuromyelitis optica (NMO) spectrum disorders patients in a territory hospital in China. The peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) were measured using spectral-domain OCT after 6 months of acute onset. The results showed that both the peripapillary RNFL and macular GCC were significantly thinner in all optic neuritis subtypes compared to controls. In addition, the recurrent optic neuritis and NMO group...

  11. Formalization of the input/output retinal transformation regarding non-standard ganglion cells behavior

    OpenAIRE

    Teftef, Elaa; Viéville, Thierry

    2012-01-01

    National audience; We propose to implement the computational principles raised by the study on the K-cells of the retina using a variational specification of the visual front-end, with an important consequence: In such a framework, the GC are not to be considered individually, but as a network, yielding a mesoscopic view of the retinal processWe consider this visual event detection mechanism to be based on image segmentation and specific natural statistical recognition, including temporal pat...

  12. Early-Onset Progressive Retinal Atrophy Associated with an IQCB1 Variant in African Black-Footed Cats (Felis nigripes)

    Science.gov (United States)

    Oh, Annie; Pearce, Jacqueline W.; Gandolfi, Barbara; Creighton, Erica K.; Suedmeyer, William K.; Selig, Michael; Bosiack, Ann P.; Castaner, Leilani J.; Whiting, Rebecca E. H.; Belknap, Ellen B.; Lyons, Leslie A.; Aderdein, Danielle; Alves, Paulo C.; Barsh, Gregory S.; Beale, Holly C.; Boyko, Adam R.; Castelhano, Marta G.; Chan, Patricia; Ellinwood, N. Matthew; Garrick, Dorian J.; Helps, Christopher R.; Kaelin, Christopher B.; Leeb, Tosso; Lohi, Hannes; Longeri, Maria; Malik, Richard; Montague, Michael J.; Munday, John S.; Murphy, William J.; Pedersen, Niels C.; Rothschild, Max F.; Swanson, William F.; Terio, Karen A.; Todhunter, Rory J.; Warren, Wesley C.

    2017-01-01

    African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management. PMID:28322220

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

    Science.gov (United States)

    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.

  14. Evaluation of the retinal nerve fibre layer and ganglion cell complex thickness in pituitary macroadenomas without optic chiasmal compression

    Science.gov (United States)

    Cennamo, G; Auriemma, R S; Cardone, D; Grasso, L F S; Velotti, N; Simeoli, C; Di Somma, C; Pivonello, R; Colao, A; de Crecchio, G

    2015-01-01

    Purpose The aim of this prospective study was to measure the thickness of the circumpapillary retinal nerve fibre layer (cpRNFL) and the ganglion cell complex (GCC) using spectral domain optical coherence tomography (SD-OCT) in a cohort of consecutive de novo patients with pituitary macroadenomas without chiasmal compression. Patients and methods Twenty-two consecutive patients with pituitary macroadenoma without chiasmal compression (16 men, 6 women, aged 45.2±14.6 years, 43 eyes) entered the study between September 2011 and June 2013. Among them, 31.8% harboured a growth hormone-secreting pituitary adenoma, 27.3% a prolactin-secreting pituitary adenoma, 27.3% a corticotrophin-secreting pituitary adenoma, and 13.6% a non-secreting pituitary tumour. Eighteen subjects (nine females, nine males, mean age 36.47±6.37 years; 33 eyes) without pituitary adenoma, with normal ophthalmic examination, served as controls. In both patients and controls, cpRNFL and GCC thicknesses were measured by SD-OCT. Results Patients were significantly older (P=0.02) than controls. Best corrected visual acuity, intraocular pressure, colour fundus photography, and automatic perimetry test were within the normal range in patients and controls. Conversely, cpRNFL (P=0.009) and GCC (P<0.0001) were significantly thinner in patients than in controls. The average GCC (r=0.306, P=0.046) significantly correlated with the presence of arterial hypertension. OCT parameters did not differ significantly between patients with a tumour volume above the median and those with a tumour volume below the median. Conclusion Pituitary macroadenomas, even in the absence of chiasmal compression, may induce GCC and retinal nerve fibre layer thinning. SD-OCT may have a role in the early diagnosis and management of patients with pituitary tumours. PMID:25853400

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Chronic intestinal pseudo-obstruction associated with enteric ganglionitis in a Persian cat

    Directory of Open Access Journals (Sweden)

    Jeremy Mortier

    2016-06-01

    Full Text Available Case summary A 7-year-old neutered male Persian cat was presented for acute vomiting and inappetence. Physical examination revealed severe abdominal distension. Radiographs demonstrated pneumoperitoneum, megaoesophagus and generalised gaseous distension of the digestive tract. Exploratory coeliotomy was performed, revealing markedly distended and thickened small and large intestines with no observable peristalsis. No intestinal perforation was present. Bacteriological and cytological analysis of abdominal fluid revealed a septic peritonitis involving Pasteurella multocida. Full-thickness intestinal biopsies demonstrated lymphocytic ganglioneuritis localised to the enteric nervous system, in association with glandular atrophy and muscular layer hypertrophy. Amoxicillin-clavulanate and analgesics were given. The cat’s general condition gradually improved after the addition of pyridostigmine bromide (0.5 mg/kg q12h PO, initiated 3 days postsurgery. Vomiting resolved and did not recur. Follow-up radiographs at 15 days, and 1 and 6 months showed persistent intestinal ileus, milder than on the pretreatment radiographs. Thirty months after presentation the cat is still alive, without clinical signs, and receives 1 mg/kg q12h pyridostigmine. Relevance and novel information To our knowledge, this is the first case of ganglioneuritis of the myenteric plexus described in cats, as well as the first one successfully treated with pyridostigmine. Chronic intestinal pseudo-obstruction is a very rare condition in cats but should be included in the differential diagnosis of generalised gastrointestinal ileus.

  17. Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.

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    Peng, Shanshan; Shi, Zhe; Su, Huanxing; So, Kwok-Fai; Cui, Qi

    2016-07-01

    Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system.

  18. Viral vector-mediated downregulation of RhoA increases survival and axonal regeneration of retinal ganglion cells

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    Jan Christoph Koch

    2014-09-01

    Full Text Available The Rho/ROCK pathway is a promising therapeutic target in neurodegenerative and neurotraumatic diseases. Pharmacological inhibition of various pathway members has been shown to promote neuronal regeneration and survival. However, because pharmacological inhibitors are inherently limited in their specificity, shRNA-mediated approaches can add more information on the function of each single kinase involved. Thus, we generated adeno-associated viral vectors (AAV to specifically downregulate RhoA via shRNA. We found that specific knockdown of RhoA promoted neurite outgrowth of retinal ganglion cells (RGC grown on the inhibitory substrate CSPG as well as neurite regeneration of primary midbrain neurons after scratch lesion. In the rat optic nerve crush model in vivo, downregulation of RhoA significantly enhanced axonal regeneration compared to control. Moreover, survival of RGCs transduced with AAV expressing RhoA-shRNA was substantially increased at two weeks after optic nerve axotomy.Compared to previous data using pharmacological inhibitors to target RhoA, its upstream regulator Nogo or its main downstream target ROCK2, the specific effects of RhoA downregulation shown here were more pronounced in regard to promoting RGC survival while the stimulatory effects on neurite outgrowth were rather moderate. Taken together, we show here that specific knockdown of RhoA substantially increases neuronal survival after optic nerve axotomy and modestly increases neurite outgrowth in vitro and axonal regeneration after optic nerve crush.

  19. Responses of retinal ganglion cells to extracellular electrical stimulation, from single cell to population: model-based analysis.

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    David Tsai

    Full Text Available Retinal ganglion cells (RGCs, which survive in large numbers following neurodegenerative diseases, could be stimulated with extracellular electric pulses to elicit artificial percepts. How do the RGCs respond to electrical stimulation at the sub-cellular level under different stimulus configurations, and how does this influence the whole-cell response? At the population level, why have experiments yielded conflicting evidence regarding the extent of passing axon activation? We addressed these questions through simulations of morphologically and biophysically detailed computational RGC models on high performance computing clusters. We conducted the analyses on both large-field RGCs and small-field midget RGCs. The latter neurons are unique to primates. We found that at the single cell level the electric potential gradient in conjunction with neuronal element excitability, rather than the electrode center location per se, determined the response threshold and latency. In addition, stimulus positioning strongly influenced the location of RGC response initiation and subsequent activity propagation through the cellular structure. These findings were robust with respect to inhomogeneous tissue resistivity perpendicular to the electrode plane. At the population level, RGC cellular structures gave rise to low threshold hotspots, which limited axonal and multi-cell activation with threshold stimuli. Finally, due to variations in neuronal element excitability over space, following supra-threshold stimulation some locations favored localized activation of multiple cells, while others favored axonal activation of cells over extended space.

  20. 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.

  1. Lack of genetic association among coat colors, progressive retinal atrophy and polycystic kidney disease in Persian cats.

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    Rah, HyungChul; Maggs, David J; Lyons, Leslie A

    2006-10-01

    An inherited form of progressive retinal atrophy (PRA) is recognized in Persian cats; however, the prevalence of PRA in the breed has not been determined. Breeders suggest that cats from only brown ('chocolate') or Himalayan ('pointed') lines are at risk for PRA, suggesting the disease is not widespread. This study was designed to evaluate whether PRA in Persian cats is associated with three coat colors, including chocolate, or with a highly prevalent inherited disease in this breed--polycystic kidney disease (PKD). Sixty related cats were evaluated for PRA by ophthalmic examination and genetically typed for PKD and the mutations that cause coat color variants in agouti, brown and color (producing the pointed coloration in Himalayan). No associations were identified among any of the traits, including between PRA and chocolate. These data suggest that PRA is not limited to cats with chocolate coat coloration and breeders and veterinarians should be aware that the prevalence of the disease may be higher than currently claimed.

  2. 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.

  3. Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.

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    Joel A Dietz

    Full Text Available The Rgcs1 quantitative trait locus, on mouse chromosome 5, influences susceptibility of retinal ganglion cells to acute damage of the optic nerve. Normally resistant mice (DBA/2J congenic for the susceptible allele from BALB/cByJ mice exhibit susceptibility to ganglion cells, not only in acute optic nerve crush, but also to chronic inherited glaucoma that is characteristic of the DBA/2J strain as they age. SNP mapping of this QTL has narrowed the region of interest to 1 Mb. In this region, a single gene (Spink2 is the most likely candidate for this effect. Spink2 is expressed in retinal ganglion cells and is increased after optic nerve damage. This gene is also polymorphic between resistant and susceptible strains, containing a single conserved amino acid change (threonine to serine and a 220 bp deletion in intron 1 that may quantitatively alter endogenous expression levels between strains. Overexpression of the different variants of Spink2 in D407 tissue culture cells also increases their susceptibility to the apoptosis-inducing agent staurosporine in a manner consistent with the differential susceptibility between the DBA/2J and BALB/cByJ strains.

  4. 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

  5. Synthetic conantokin peptides potently inhibit N-methyl-D-aspartate receptor-mediated currents of retinal ganglion cells.

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    Huang, Luoxiu; Balsara, Rashna D; Castellino, Francis J

    2014-12-01

    Retinal ganglion cells (RGCs), which are the sole output neurons of the retina, express N-methyl-D-aspartate receptors (NMDARs), rendering these cells susceptible to glutamate excitotoxicity, with implications for loss of normal RGC excitatory responses in disorders such as glaucoma and diabetic retinopathy. Therefore, antagonists that inhibit NMDAR-mediated currents specifically by targeting the GluN2B component of the ion channel have the potential to serve as a basis for developing potential therapeutics. The roles of peptidic conantokins, which are potent brain neuronal NMDAR inhibitors, were studied. By using patch-clamp whole-cell analyses in dissociated RGCs and retinal whole-mount RGCs, we evaluated the effects of synthetic conantokin-G (conG) and conantokin-T (conT), which are small γ-carboxyglutamate-containing peptides, on NMDA-mediated excitatory responses in mouse RGCs. Both conG and conT inhibited the NMDA-mediated currents of dark-adapted dissociated and whole-mount RGCs in a dose-dependent, reversible, noncompetitive manner. Inhibition of NMDA-mediated steady-state currents by NMDAR nonsubunit-selective conT was approximately threefold greater than GluN2B-selective conG or ifenprodil, demonstrating its potential ability to inhibit both GluN2A- and GluN2B-containing ion channels in RGCs. Because the extent of inhibition of NMDA-evoked currents by conG and the pharmacologic GluN2B-selective inhibitor ifenprodil were similar (40-45%) to that of the GluN2A-selective antagonist NVP-AAM0077, we conclude that the levels of GluN2A and GluN2B subunits are similar in RGCs. These results provide a novel basis for developing effective neuroprotective agents to aid in the prevention of undesired glutamatergic excitotoxicity in neurodegenerative diseases of the retina and demonstrate functional assembly of NMDARs in RGCs.

  6. Kv3 channels modulate calcium signals induced by fast firing patterns in the rat retinal ganglion cells.

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    Kuznetsov, Kirill I; Grygorov, Oleksii O; Maslov, Vitaly Yu; Veselovsky, Nikolay S; Fedulova, Svetlana A

    2012-11-01

    Expression of non-inactivating Kv3.1/Kv3.2 potassium channels determines fast-spiking phenotype of many types of neurones including retinal ganglion cells (RGCs); furthermore Kv3 channels regulate neurotransmitter release from presynaptic terminals. In the present study we investigated how inhibition of Kv3 channel by low TEA concentrations modifies firing properties and Ca2+ influx in the rat RGCs. Experiments were performed on the whole-mount retinal preparations from 4 to 6 weeks old Wistar rats using simultaneous whole cell patch clamp and intracellular Ca2+ measurements in combination with single-cell RT-PCR. In response to 500-ms depolarization step the RGCs demonstrated fast firing tonic behaviour with a mean frequency of spiking 61±5 Hz (n=28). All of the tonic cells tested (n=9) expressed specific mRNA for either Kv3.1 or Kv3.2 or for both channels. Bath applications of TEA (250 μM, 500 μM and 1 mM) modified firing patterns dose-dependently as follows: firing frequency was decreased, mean action potential (AP) half-width increased and mean amplitude of after hyperpolarization was reduced. The amplitude of the Ca2+ signals induced by the cells firing was linearly dependent on number of APs with a mean slope of 7.3±0.9 nM per one AP (n=8). APs widening by TEA increased the slope of the amplitude vs. AP number plots in a dose-dependent manner: 250 μM of TEA increased the mean slope value to 9.5±1.2 nM/AP, 500 μM to 12.4±2.4 nM/AP and 1 mM to 13.2±2.9 nM/AP (n=6). All these parameters, as well as the cells firing properties, were significantly different from controls and from each other except between 500 μM and 1 mM. This is consistent with the pharmacological properties of Kv3.1/Kv3.2 channels: the TEA IC50 is in the range 150-300 μM with almost complete block at 1 mM. This suggests that Kv3.1/Kv3.2 channels underlie the fast firing of the rat RGCs and provide at a given firing frequency 1.8-fold restriction Ca2+ influx, thus protecting the cells

  7. Receptive Field Vectors of Genetically-Identified Retinal Ganglion Cells Reveal Cell-Type-Dependent Visual Functions.

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    Matthew L Katz

    Full Text Available Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs which utilises a modified form of mutual information ("Quadratic Mutual Information". We analysed the firing patterns of RGCs during presentation of short duration (~10 second complex visual scenes (natural movies. We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells' response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types.

  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. Protective action of nipradilol mediated through S-nitrosylation of Keap1 and HO-1 induction in retinal ganglion cells.

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    Koriyama, Yoshiki; Kamiya, Marie; Takadera, Tsuneo; Arai, Kunizo; Sugitani, Kayo; Ogai, Kazuhiro; Kato, Satoru

    2012-12-01

    Nipradilol (Nip), which has α1- and β-adrenoceptor antagonist and nitric oxide (NO)-donating properties, has clinically been used as an anti-glaucomatous agent in Japan. NO mediates cellular signaling pathways that regulate physiological functions. The major signaling mechanisms mediated by NO are cGMP-dependent signaling and protein S-nitrosylation-dependent signalings. Nip has been described as having neuroprotective effects through cGMP-dependent pathway in retinal ganglion cells (RGCs). However, the effect seems to be partial. On the other hand, whether Nip can prevent cell death through S-nitrosylation is not yet clarified. In this study, we therefore focused on the neuroprotective mechanism of Nip through S-nitrosylation. Nip showed a dramatic neuroprotective effect against oxidative stress-induced death of RGC-5 cells. However, denitro-nipradilol, which does not have NO-donating properties, was not protective against oxidative stress. Furthermore, an NO scavenger significantly reversed the protective action of Nip against oxidative stress. In addition, we demonstrated that α1- or β-adrenoceptor antagonists (prazosin or timolol) did not show any neuroprotective effect against oxidative stress in RGC-5 cells. We also demonstrated that Nip induced the expression of the NO-dependent antioxidant enzyme, heme oxygenase-1 (HO-1). S-nitrosylation of Kelch-like ECH-associated protein by Nip was shown to contribute to the translocation of NF-E2-related factor 2 to the nucleus, and triggered transcriptional activation of HO-1. Furthermore, RGC death and levels of 4-hydroxy-2-nonenal (4HNE) were increased after optic nerve injury in vivo. Pretreatment with Nip significantly suppressed RGC death and accumulation of 4HNE after injury through an HO-1 activity-dependent mechanism. These data demonstrate a novel neuroprotective action of Nip against oxidative stress-induced RGC death in vitro and in vivo.

  10. 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.

  11. A Single Nucleotide Polymorphism in the Bax Gene Promoter Affects Transcription and Influences Retinal Ganglion Cell Death

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    Sheila J Semaan

    2010-03-01

    Full Text Available Pro-apoptotic Bax is essential for RGC (retinal ganglion cell death. Gene dosage experiments in mice, yielding a single wild-type Bax allele, indicated that genetic background was able to influence the cell death phenotype. DBA/2J Bax+/− mice exhibited complete resistance to nerve damage after 2 weeks (similar to Bax −/− mice, but 129B6 Bax+/− mice exhibited significant cell loss (similar to wild-type mice. The different cell death phenotype was associated with the level of Bax expression, where 129B6 neurons had twice the level of endogenous Bax mRNA and protein as DBA/2J neurons. Sequence analysis of the Bax promoters between these strains revealed a single nucleotide polymorphism (T129B6 to CDBA/2J at position −515. A 1.5- to 2.5-fold increase in transcriptional activity was observed from the 129B6 promoter in transient transfection assays in a variety of cell types, including RGC5 cells derived from rat RGCs. Since this polymorphism occurred in a p53 half-site, we investigated the requirement of p53 for the differential transcriptional activity. Differential transcriptional activity from either 129B6 or DBA/2J Bax promoters were unaffected in p53−/− cells, and addition of exogenous p53 had no further effect on this difference, thus a role for p53 was excluded. Competitive electrophoretic mobility-shift assays identified two DNA-protein complexes that interacted with the polymorphic region. Those forming Complex 1 bound with higher affinity to the 129B6 polymorphic site, suggesting that these proteins probably comprised a transcriptional activator complex. These studies implicated quantitative expression of the Bax gene as playing a possible role in neuronal susceptibility to damaging stimuli.

  12. 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.

  13. DRP1 inhibition rescues retinal ganglion cells and their axons by preserving mitochondrial integrity in a mouse model of glaucoma.

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    Kim, K-Y; Perkins, G A; Shim, M S; Bushong, E; Alcasid, N; Ju, S; Ellisman, M H; Weinreb, R N; Ju, W-K

    2015-08-06

    Glaucoma is the leading cause of irreversible blindness and is characterized by slow and progressive degeneration of the optic nerve head axons and retinal ganglion cell (RGC), leading to loss of visual function. Although oxidative stress and/or alteration of mitochondrial (mt) dynamics induced by elevated intraocular pressure (IOP) are associated with this neurodegenerative disease, the mechanisms that regulate mt dysfunction-mediated glaucomatous neurodegeneration are poorly understood. Using a mouse model of glaucoma, DBA/2J (D2), which spontaneously develops elevated IOP, as well as an in vitro RGC culture system, we show here that oxidative stress, as evidenced by increasing superoxide dismutase 2 (SOD2) and mt transcription factor A (Tfam) protein expression, triggers mt fission and loss by increasing dynamin-related protein 1 (DRP1) in the retina of glaucomatous D2 mice as well as in cultured RGCs exposed to elevated hydrostatic pressure in vitro. DRP1 inhibition by overexpressing DRP1 K38A mutant blocks mt fission and triggers a subsequent reduction of oxidative stress, as evidenced by decreasing SOD2 and Tfam protein expression. DRP1 inhibition promotes RGC survival by increasing phosphorylation of Bad at serine 112 in the retina and preserves RGC axons by maintaining mt integrity in the glial lamina of glaucomatous D2 mice. These findings demonstrate an important vicious cycle involved in glaucomatous neurodegeneration that starts with elevated IOP producing oxidative stress; the oxidative stress then leads to mt fission and a specific form of mt dysfunction that generates further oxidative stress, thus perpetuating the cycle. Our findings suggest that DRP1 is a potential therapeutic target for ameliorating oxidative stress-mediated mt fission and dysfunction in RGC and its axons during glaucomatous neurodegeneration. Thus, DRP1 inhibition may provide a new therapeutic strategy for protecting both RGCs and their axons in glaucoma and other optic

  14. Differential regulation of arylalkylamine N-acetyltransferase activity in chicken retinal ganglion cells by light and circadian clock.

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    Valdez, Diego J; Garbarino-Pico, Eduardo; Díaz, Nicolás M; Silvestre, David C; Guido, Mario E

    2012-10-01

    Retinal ganglion cells (RGCs) contain circadian clocks driving melatonin synthesis during the day, a subset of these cells acting as nonvisual photoreceptors sending photic information to the brain. In this work, the authors investigated the temporal and light regulation of arylalkylamine N-acetyltransferase (AA-NAT) activity, a key enzyme in melatonin synthesis. The authors first examined this activity in RGCs of wild-type chickens and compared it to that in photoreceptor cells (PRs) from animals maintained for 48 h in constant dark (DD), light (LL), or regular 12-h:12-h light-dark (LD) cycle. AA-NAT activity in RGCs displayed circadian rhythmicity, with highest levels during the subjective day in both DD and LL as well as in the light phase of the LD cycle. In contrast, AA-NAT activity in PRs exhibited the typical nocturnal peak in DD and LD, but no detectable oscillation was observed under LL, under which conditions the levels were basal at all times examined. A light pulse of 30-60 min significantly decreased AA-NAT activity in PRs during the subjective night, but had no effect on RGCs during the day or night. Intraocular injection of dopamine (50 nmol/eye) during the night to mimic the effect of light presented significant inhibition of AA-NAT activity in PRs compared to controls but had no effect on RGCs. The results clearly demonstrate that the regulation of the diurnal increase in AA-NAT activity in RGCs of chickens undergoes a different control mechanism from that observed in PRs, in which the endogenous clock, light, and dopamine exhibited differential effects.

  15. Characteristic patterns of dendritic remodeling in early-stage glaucoma: evidence from genetically identified retinal ganglion cell types.

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    El-Danaf, Rana N; Huberman, Andrew D

    2015-02-11

    Retinal ganglion cell (RGC) loss is a hallmark of glaucoma and the second leading cause of blindness worldwide. The type and timing of cellular changes leading to RGC loss in glaucoma remain incompletely understood, including whether specific RGC subtypes are preferentially impacted at early stages of this disease. Here we applied the microbead occlusion model of glaucoma to different transgenic mouse lines, each expressing green fluorescent protein in 1-2 specific RGC subtypes. Targeted filling, reconstruction, and subsequent comparison of the genetically identified RGCs in control and bead-injected eyes revealed that some subtypes undergo significant dendritic rearrangements as early as 7 d following induction of elevated intraocular pressure (IOP). By comparing specific On-type, On-Off-type and Off-type RGCs, we found that RGCs that target the majority of their dendritic arbors to the scleral half or "Off" sublamina of the inner plexiform layer (IPL) undergo the greatest changes, whereas RGCs with the majority of their dendrites in the On sublamina did not alter their structure at this time point. Moreover, M1 intrinsically photosensitive RGCs, which functionally are On RGCs but structurally stratify their dendrites in the Off sublamina of the IPL, also underwent significant changes in dendritic structure 1 week after elevated IOP. Thus, our findings reveal that certain RGC subtypes manifest significant changes in dendritic structure after very brief exposure to elevated IOP. The observation that RGCs stratifying most of their dendrites in the Off sublamina are first to alter their structure may inform the development of new strategies to detect, monitor, and treat glaucoma in humans.

  16. 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

  17. 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

    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......-localized in their projections in the suprachiasmatic nucleus, the intergeniculate leaflet, and the olivary pretectal nucleus. We conclude that there is evidence to support the use of glutamate and PACAP as neurotransmitters in NIF photoperception by rat ipRGCs, and that these neurotransmitters are co-stored and probably...

  18. Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Complex in Patients with Optic Neuritis or Neuromyelitis Optica Spectrum Disorders Using Optical Coherence Tomography in a Chinese Cohort

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    Guohong Tian

    2015-01-01

    Full Text Available We evaluate a cohort of optic neuritis and neuromyelitis optica (NMO spectrum disorders patients in a territory hospital in China. The peripapillary retinal nerve fiber layer (RNFL and macular ganglion cell complex (GCC were measured using spectral-domain OCT after 6 months of acute onset. The results showed that both the peripapillary RNFL and macular GCC were significantly thinner in all optic neuritis subtypes compared to controls. In addition, the recurrent optic neuritis and NMO groups showed more severe damage on the RNFL and GCC pattern.

  19. Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Complex in Patients with Optic Neuritis or Neuromyelitis Optica Spectrum Disorders Using Optical Coherence Tomography in a Chinese Cohort.

    Science.gov (United States)

    Tian, Guohong; Li, Zhenxin; Zhao, Guixian; Feng, Chaoyi; Li, Mengwei; Huang, Yongheng; Sun, Xinghuai

    2015-01-01

    We evaluate a cohort of optic neuritis and neuromyelitis optica (NMO) spectrum disorders patients in a territory hospital in China. The peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) were measured using spectral-domain OCT after 6 months of acute onset. The results showed that both the peripapillary RNFL and macular GCC were significantly thinner in all optic neuritis subtypes compared to controls. In addition, the recurrent optic neuritis and NMO groups showed more severe damage on the RNFL and GCC pattern.

  20. Effects of minocycline on apoptosis and neuronal changes in retinal ganglion cells from experimental optic neuritis rats

    Institute of Scientific and Technical Information of China (English)

    Jing Zhang

    2008-01-01

    BACKGROUND: Minocycline, a tetracycline derivative, is neuroprotective in models of various neurological diseases.OBJECTIVE: To investigate the effects of minocycline on retinal ganglion cells (RGCs) in rats with optic neuritis, and to compare with the effects of methylprednisolone.DESIGN, TIME AND SETTING: This neuropathology controlled study was performed at the First Affiliated Hospital, Chongqing Medical University, China in May 2007.MATERIALS: A total of 22 female Wistar rats were randomly assigned into a normal control group (n = 5) and an experimental group (n = 17). The experimental group was composed of a model subgroup (n = 7), a minocycline subgroup (n = 5), and a methylprednisolone subgroup (n = 5). Minocycline was supplied by Sigma, USA.METHODS: Antigen homogenate made from guinea pig spinal cord and complete Freund adjuvant was used to induce autoimmune encephalomyelitis, which could induce demyelinated optic neuritis models. Rats in the minocycline subgroup were intraperitoneally injected with minocycline (45 mg/kg) daily from day 8 following autoimmunity. Rats in the methylprednisolone subgroup were intraperitoneally injected with methylprednisolone (20 mg/kg) daily from day 8 following autoimmunity.MAIN OUTCOME MEASURES: On day 18 after autoimmunity induction, pathological changes in the optic nerve were observed by hematoxylin-eosin staining. The percentage area of axons in the transverse section of the optic nerve was measured by Bielschowsky staining. Apoptosis of RGCs was detected by TUNEL.RESULTS: Under an optical microscope, the optic nerve in rats with demyelinated optic neuritis showed a vacuole-like structure of fibers, irregular swelling of the axons, and infiltration of a large quantity of inflammatory cells. With an electron microscope, the optic nerve presented with vacuole-like structures in the axons, a small percentage area of axons in the transverse section, loose myelin sheaths, and microtubules and microfilaments disappeared. The

  1. The A3 adenosine receptor attenuates the calcium rise triggered by NMDA receptors in retinal ganglion cells.

    Science.gov (United States)

    Zhang, Mei; Hu, Huiling; Zhang, Xiulan; Lu, Wennan; Lim, Jason; Eysteinsson, Thor; Jacobson, Kenneth A; Laties, Alan M; Mitchell, Claire H

    2010-01-01

    The A(3) adenosine receptor is emerging as an important regulator of neuronal signaling, and in some situations receptor stimulation can limit excitability. As the NMDA receptor frequently contributes to neuronal excitability, this study examined whether A(3) receptor activation could alter the calcium rise accompanying NMDA receptor stimulation. Calcium levels were determined from fura-2 imaging of isolated rat retinal ganglion cells as these neurons possess both receptor types. Brief application of glutamate or NMDA led to repeatable and reversible elevations of intracellular calcium. The A(3) agonist Cl-IB-MECA reduced the response to both glutamate and NMDA. While adenosine mimicked the effect of Cl-IB-MECA, the A(3) receptor antagonist MRS 1191 impeded the block by adenosine, implicating a role for the A(3) receptor in response to the natural agonist. The A(1) receptor antagonist DPCPX provided additional inhibition, implying a contribution from both A(1) and A(3) adenosine receptors. The novel A(3) agonist MRS 3558 (1'S,2'R,3'S,4'R,5'S)-4-(2-chloro-6-(3-chlorobenzylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo [3.1.0] hexane-1-carboxamide and mixed A(1)/A(3) agonist MRS 3630 (1'S,2'R,3'S,4'R,5'S)-4-(2-chloro-6-(cyclopentylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo [3.1.0] hexane-1-carboxamide also inhibited the calcium rise induced by NMDA. Low levels of MRS 3558 were particularly effective, with an IC(50) of 400 pM. In all cases, A(3) receptor stimulation inhibited only 30-50% of the calcium rise. In summary, stimulation of the A(3) adenosine receptor by either endogenous or synthesized agonists can limit the calcium rise accompanying NMDA receptor activation. It remains to be determined if partial block of the calcium rise by A(3) agonists can modify downstream responses to NMDA receptor stimulation.

  2. Expression of novel opsins and intrinsic light responses in the mammalian retinal ganglion cell line RGC-5. Presence of OPN5 in the rat retina.

    Directory of Open Access Journals (Sweden)

    Paula S Nieto

    Full Text Available The vertebrate retina is known to contain three classes of photoreceptor cells: cones and rods responsible for vision, and intrinsically photoresponsive retinal ganglion cells (RGCs involved in diverse non-visual functions such as photic entrainment of daily rhythms and pupillary light responses. In this paper we investigated the potential intrinsic photoresponsiveness of the rat RGC line, RGC-5, by testing for the presence of visual and non-visual opsins and assessing expression of the immediate-early gene protein c-Fos and changes in intracellular Ca(2+ mobilization in response to brief light pulses. Cultured RGC-5 cells express a number of photopigment mRNAs such as retinal G protein coupled receptor (RGR, encephalopsin/panopsin (Opn3, neuropsin (Opn5 and cone opsin (Opn1mw but not melanopsin (Opn4 or rhodopsin. Opn5 immunoreactivity was observed in RGC-5 cells and in the inner retina of rat, mainly localized in the ganglion cell layer (GCL. Furthermore, white light pulses of different intensities and durations elicited changes both in intracellular Ca(2+ levels and in the induction of c-Fos protein in RGC-5 cell cultures. The results demonstrate that RGC-5 cells expressing diverse putative functional photopigments display intrinsic photosensitivity which accounts for the photic induction of c-Fos protein and changes in intracellular Ca(2+ mobilization. The presence of Opn5 in the GCL of the rat retina suggests the existence of a novel type of photoreceptor cell.

  3. 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.

  4. 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.

  5. 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

    2017-01-01

    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. PMID:28067793

  6. Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina

    Science.gov (United States)

    Jensen, Ralph J.; Rizzo, Joseph F., III

    2011-06-01

    An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABAC receptor antagonist, and SR95531, a GABAA receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 µm diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells.

  7. The CORM ALF-186 Mediates Anti-Apoptotic Signaling via an Activation of the p38 MAPK after Ischemia and Reperfusion Injury in Retinal Ganglion Cells

    Science.gov (United States)

    Ulbrich, Felix; Kaufmann, Kai B.; Meske, Alexander; Lagrèze, Wolf A.; Augustynik, Michael; Buerkle, Hartmut; Ramao, Carlos C.; Biermann, Julia

    2016-01-01

    Purpose Ischemia and reperfusion injury may induce apoptosis and lead to sustained tissue damage and loss of function, especially in neuronal organs. While carbon monoxide is known to exert protective effects after various harmful events, the mechanism of carbon monoxide releasing molecules in neuronal tissue has not been investigated yet. We hypothesize that the carbon monoxide releasing molecule (CORM) ALF-186, administered after neuronal ischemia-reperfusion injury (IRI), counteracts retinal apoptosis and its involved signaling pathways and consecutively reduces neuronal tissue damage. Methods IRI was performed in rat´s retinae for 1 hour. The water-soluble CORM ALF-186 (10 mg/kg) was administered intravenously via a tail vein after reperfusion. After 24 and 48 hours, retinal tissue was harvested to analyze mRNA and protein expression of Bcl-2, Bax, Caspase-3, ERK1/2, p38 and JNK. Densities of fluorogold pre-labeled retinal ganglion cells (RGC) were analyzed 7 days after IRI. Immunohistochemistry was performed on retinal cross sections. Results ALF-186 significantly reduced IRI mediated loss of RGC. ALF-186 treatment differentially affected mitogen-activated protein kinases (MAPK) phosphorylation: ALF-186 activated p38 and suppressed ERK1/2 phosphorylation, while JNK remained unchanged. Furthermore, ALF-186 treatment affected mitochondrial apoptosis, decreasing pro-apoptotic Bax and Caspase-3-cleavage, but increasing anti-apoptotic Bcl-2. Inhibition of p38-MAPK using SB203580 reduced ALF-186 mediated anti-apoptotic effects. Conclusion In this study, ALF-186 mediated substantial neuroprotection, affecting intracellular apoptotic signaling, mainly via MAPK p38. CORMs may thus represent a promising therapeutic alternative treating neuronal IRI. PMID:27764224

  8. Representation of the visual field in the primary visual area of the marmoset monkey: magnification factors, point-image size, and proportionality to retinal ganglion cell density.

    Science.gov (United States)

    Chaplin, Tristan A; Yu, Hsin-Hao; Rosa, Marcello G P

    2013-04-01

    The primary visual area (V1) forms a systematic map of the visual field, in which adjacent cell clusters represent adjacent points of visual space. A precise quantification of this map is key to understanding the anatomical relationships between neurons located in different stations of the visual pathway, as well as the neural bases of visual performance in different regions of the visual field. We used computational methods to quantify the visual topography of V1 in the marmoset (Callithrix jacchus), a small diurnal monkey. The receptive fields of neurons throughout V1 were mapped in two anesthetized animals using electrophysiological recordings. Following histological reconstruction, precise 3D reconstructions of the V1 surface and recording sites were generated. We found that the areal magnification factor (M(A) ) decreases with eccentricity following a function that has the same slope as that observed in larger diurnal primates, including macaque, squirrel, and capuchin monkeys, and humans. However, there was no systematic relationship between M(A) and polar angle. Despite individual variation in the shape of V1, the relationship between M(A) and eccentricity was preserved across cases. Comparison between V1 and the retinal ganglion cell density demonstrated preferential magnification of central space in the cortex. The size of the cortical compartment activated by a punctiform stimulus decreased from the foveal representation towards the peripheral representation. Nonetheless, the relationship between the receptive field sizes of V1 cells and the density of ganglion cells suggested that each V1 cell receives information from a similar number of retinal neurons, throughout the visual field.

  9. 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

    2016-11-17

    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.

  10. 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

    PURPOSE: To investigate retinal trunk vessel diameters in subjects with autosomal dominant optic atrophy (ADOA) and mutation-free healthy relatives. METHODS: This cross-sectional study included 52 ADOA patients with the optic atrophy 1 (OPA1) exon 28 (c.2826_2836delinsGGATGCTCCA) mutation (age 8....... are a consequence rather than the cause of inner retinal hypoplasia or atrophy, although longitudinal studies are needed to confirm this hypothesis....

  11. Effects of bicarbonate buffer on acetylcholine-, adenosine 5'triphosphate-, and cyanide-induced responses in the cat petrosal ganglion in vitro.

    Science.gov (United States)

    Soto, Carolina R; Arroyo, Jorge; Alcayaga, Julio

    2002-01-01

    Acetylcholine (ACh), adenosine 5'-triphosphate (ATP) and sodium cyanide (NaCN) activate petrosal ganglion (PG) neurons in vitro, and evoke ventilatory reflexes in situ, which are abolished after bilateral chemosensory denervation. Because in our previous experiments we superfused the isolated PG with solutions free of CO2/HCO3- buffer, we studied its effects on the PG responses evoked in vitro. PGs from adult cats were superfused at a constant pH, with HEPES-supplemented (5 mM) saline with or without CO2/HCO3- (5%/26.2 mM) buffer, and carotid (sinus) nerve frequency discharge (fCN) recorded. Increases in fCN evoked by ACh, ATP and NaCN in CO2- free saline were significantly reduced (P buffer appears to reduce PG neurons sensitivity to ACh, ATP and NaCN, an effect that may underlie the lack of ventilatory reflexes after bilateral chemodenervation.

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

    Science.gov (United States)

    Xie, Bin-Bin; Zhang, Xiang-Mei; Hashimoto, Takao; Tien, Amy H; Chen, Andrew; Ge, Jian; Yang, Xian-Jie

    2014-01-01

    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.

  13. Neuroprotective effects of Argon are mediated via an ERK-1/2 dependent regulation of heme-oxygenase-1 in retinal ganglion cells.

    Science.gov (United States)

    Ulbrich, Felix; Kaufmann, Kai B; Coburn, Mark; Lagrèze, Wolf Alexander; Roesslein, Martin; Biermann, Julia; Buerkle, Hartmut; Loop, Torsten; Goebel, Ulrich

    2015-08-01

    Retinal ischemia and reperfusion injuries (R-IRI) damage neuronal tissue permanently. Recently, we demonstrated that Argon exerts anti-apoptotic and protective properties. The molecular mechanism remains unclear. We hypothesized that Argon inhalation exert neuroprotective effects in rats retinal ganglion cells (RGC) via an ERK-1/2 dependent regulation of heat-shock proteins. Inhalation of Argon (75 Vol%) was performed after R-IRI on the rats' left eyes for 1 h immediately or with delay. Retinal tissue was harvested after 24 h to analyze mRNA and protein expression of heat-shock proteins -70, -90 and heme-oxygenase-1, mitogen-activated protein kinases (p38, JNK, ERK-1/2) and histological changes. To analyze ERK dependent effects, the ERK inhibitor PD98059 was applicated prior to Argon inhalation. RGC count was analyzed 7 days after injury. Statistics were performed using anova. Argon significantly reduced the R-IRI-affected heat-shock protein expression (p ERK-1/2 expression (p ERK-1/2 before Argon inhalation resulted in significantly lower vital RGCs (p ERK-1/2 activation in Müller cells. We conclude, that Argon treatment protects R-IRI-induced apoptotic loss of RGC via an ERK-1/2 dependent regulation of heme-oxygenase-1. We proposed the following possible mechanism for Argon-mediated neuroprotection: Argon exerts its protective effects via an induction of an ERK with subsequent suppression of the heat shock response. In conclusion, ischemia and reperfusion injuries and subsequent neuronal apoptosis are attenuated. These novel findings may open up new opportunities for Argon as a therapeutic option, especially since Argon is not toxic.

  14. 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.

  15. 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

    regenerative therapies, an improved understanding of axonal outgrowth and the various molecules influencing it, is highly needed. Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases that were sporadically reported to influence axon outgrowth. Using an ex vivo retinal explant model...

  16. 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.

  17. Combined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma.

    Science.gov (United States)

    Fu, Q-L; Li, X; Yip, H K; Shao, Z; Wu, W; Mi, S; So, K-F

    2009-08-18

    Glaucoma is a progressive neuropathy characterized by loss of vision as a result of retinal ganglion cell (RGC) death. There are no effective neuroprotectants to treat this disorder. Brain-derived neurotrophic factor (BDNF) is well known to transiently delay RGC death in ocular hypertensive eyes. The CNS-specific leucine-rich repeat protein LINGO-1 contributes to the negative regulation to some trophic pathways. We thereby examined whether BDNF combined with LINGO-1 antagonists can promote long-term RGC survival after ocular hypertension. In this study, intraocular pressure was elevated in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. BDNF alone shows slight neuroprotection to RGCs after a long-term progress of 4 weeks following the induction of ocular hypertension. However, combination of BDNF and LINGO-1-Fc prevents RGC death in the same condition. We further identified that (1) LINGO-1 was co-expressed with BDNF receptor, TrkB in the RGCs, and (2) BDNF combined with LINGO-1-Fc activated more TrkB in the injured retina compared to BDNF alone. These results indicate that the combination of BDNF with LINGO-1 antagonist can provide long-term protection for RGCs in a chronic ocular hypertension model. TrkB may be the predominant mediator of this neuroprotection.

  18. 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.

  19. Cytochrome c release and caspase-3 activation in retinal ganglion cells following different distance of axotomy of the optic nerve in adult hamsters.

    Science.gov (United States)

    He, M H; Cheung, Z H; Yu, E H; Tay, D K C; So, K F

    2004-11-01

    This study examined the relationship between the distance of axotomy and the death of injured retinal ganglion cells (RGCs) in adult hamsters and the relationship of cytochrome c and caspase-3 on the death pathway of RGCs. The left optic nerve (ON) of adult hamsters was transected either at 1 or 3 mm away from the optic disc, and retrogradely labeled with Flurogold on the ON stump. After a predetermined period of postoperative time, the surviving RGCs were counted by retina flat-mount, and the activation of cytochrome c and caspase-3 were investigated by immunohistochemistry. Cell loss was found to be much faster (P < 0.01), more cells with cytochrome c were observed (P < 0.05) and the activation of caspase-3 was earlier when ON was transected 1 mm away from the optic disc than when was transected 3 mm away from the optic disc. Distance of axotomy affects the axotomized cell death rate where more RGCs died when the ON transection was applied closer to the eye. The timing of activation of caspase-3 in the RGCs may be linked to the distance of axotomy.

  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. Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4 Show Increased Vulnerability of Retinal Ganglion Cells to Elevated Intraocular Pressure.

    Science.gov (United States)

    Gao, Shan; Jakobs, Tatjana C

    2016-04-01

    A genomic region located on chromosome 9p21 is associated with primary open-angle glaucoma and normal tension glaucoma in genome-wide association studies. The genomic region contains the gene for a long noncoding RNA called CDKN2B-AS, two genes that code for cyclin-dependent kinase inhibitors 2A and 2B (CDKN2A/p16(INK4A) and CDKN2B/p15(INK4B)) and an additional protein (p14(ARF)). We used a transgenic mouse model in which 70 kb of murine chromosome 4, syntenic to human chromosome 9p21, are deleted to study whether this deletion leads to a discernible phenotype in ocular structures implicated in glaucoma. Homozygous mice of this strain were previously reported to show persistent hyperplastic primary vitreous. Fundus photography and optical coherence tomography confirmed that finding but showed no abnormalities for heterozygous mice. Optokinetic response, eletroretinogram, and histology indicated that the heterozygous and mutant retinas were normal functionally and morphologically, whereas glial cells were activated in the retina and optic nerve head of mutant eyes. In quantitative PCR, CDKN2B expression was reduced by approximately 50% in the heterozygous mice and by 90% in the homozygous mice, which suggested that the CDKN2B knock down had no deleterious consequences for the retina under normal conditions. However, compared with wild-type and heterozygous animals, the homozygous mice are more vulnerable to retinal ganglion cell loss in response to elevated intraocular pressure.

  2. Influence of optic disc size on the diagnostic performance of macular ganglion cell complex and peripapillary retinal nerve fiber layer analyses in glaucoma

    Directory of Open Access Journals (Sweden)

    Cordeiro DV

    2011-09-01

    Full Text Available Daniela Valença Cordeiro1, Verônica Castro Lima1,2, Dinorah P Castro1,3, Leonardo C Castro1,3, Maria Angélica Pacheco2, Jae Min Lee2, Marcelo I Dimantas2, Tiago Santos Prata1,21Department of Ophthalmology, Federal University of São Paulo, São Paulo, 2Hospital Medicina dos Olhos, São Paulo, 3Centro Brasileiro de Especialidades Oftalmológicas, Araraquara, BrazilAim: To evaluate the influence of optic disc size on the diagnostic accuracy of macular ganglion cell complex (GCC and conventional peripapillary retinal nerve fiber layer (pRNFL analyses provided by spectral domain optical coherence tomography (SD-OCT in glaucoma.Methods: Eighty-two glaucoma patients and 30 healthy subjects were included. All patients underwent GCC (7 × 7 mm macular grid, consisting of RNFL, ganglion cell and inner plexiform layers and pRNFL thickness measurement (3.45 mm circular scan by SD-OCT. One eye was randomly selected for analysis. Initially, receiver operating characteristic (ROC curves were generated for different GCC and pRNFL parameters. The effect of disc area on the diagnostic accuracy of these parameters was evaluated using a logistic ROC regression model. Subsequently, 1.5, 2.0, and 2.5 mm2 disc sizes were arbitrarily chosen (based on data distribution and the predicted areas under the ROC curves (AUCs and sensitivities were compared at fixed specificities for each.Results: Average mean deviation index for glaucomatous eyes was -5.3 ± 5.2 dB. Similar AUCs were found for the best pRNFL (average thickness = 0.872 and GCC parameters (average thickness = 0.824; P = 0.19.The coefficient representing disc area in the ROC regression model was not statistically significant for average pRNFL thickness (-0.176 or average GCC thickness (0.088; P ≥ 0.56. AUCs for fixed disc areas (1.5, 2.0, and 2.5 mm2 were 0.904, 0.891, and 0.875 for average pRNFL thickness and 0.834, 0.842, and 0.851 for average GCC thickness, respectively. The highest sensitivities – at

  3. 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

    Hg below mean arterial blood pressure for 2 h. The mean IOP during the ischemic insult was 79.5 mmHg (s.e.m. 2.1 mmHg, n = 15). Three days after the insult the pigs received an intravitreal injection of GDNF microspheres or blank microspheres. The pigs were evaluated by way of multifocal.......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 ... injected with GDNF microspheres compared to eyes injected with blank microspheres. In eyes injected with GDNF microspheres the ganglion cell count was 9.5/field (s.e.m.: 2.1, n = 8), in eyes injected with blank microspheres it was 3.5/field (s.e.m.: 1.2, n = 7). This difference was statistically...

  4. Effects of brain-derived neurotrophic factor (BDNF) and electrical stimulation on survival and function of cochlear spiral ganglion neurons in deafened, developing cats.

    Science.gov (United States)

    Leake, Patricia A; Stakhovskaya, Olga; Hetherington, Alexander; Rebscher, Stephen J; Bonham, Ben

    2013-04-01

    Both neurotrophic support and neural activity are required for normal postnatal development and survival of cochlear spiral ganglion (SG) neurons. Previous studies in neonatally deafened cats demonstrated that electrical stimulation (ES) from a cochlear implant can promote improved SG survival but does not completely prevent progressive neural degeneration. Neurotrophic agents combined with an implant may further improve neural survival. Short-term studies in rodents have shown that brain-derived neurotrophic factor (BDNF) promotes SG survival after deafness and may be additive to trophic effects of stimulation. Our recent study in neonatally deafened cats provided the first evidence of BDNF neurotrophic effects in the developing auditory system over a prolonged duration Leake et al. (J Comp Neurol 519:1526-1545, 2011). Ten weeks of intracochlear BDNF infusion starting at 4 weeks of age elicited significant improvement in SG survival and larger soma size compared to contralateral. In the present study, the same deafening and BDNF infusion procedures were combined with several months of ES from an implant. After combined BDNF + ES, a highly significant increase in SG numerical density (>50 % improvement re: contralateral) was observed, which was significantly greater than the neurotrophic effect seen with ES-only over comparable durations. Combined BDNF + ES also resulted in a higher density of myelinated radial nerve fibers within the osseous spiral lamina. However, substantial ectopic and disorganized sprouting of these fibers into the scala tympani also occurred, which may be deleterious to implant function. EABR thresholds improved (re: initial thresholds at time of implantation) on the chronically stimulated channels of the implant. Terminal electrophysiological studies recording in the inferior colliculus (IC) revealed that the basic cochleotopic organization was intact in the midbrain in all studied groups. In deafened controls or after ES-only, lower IC

  5. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  6. 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

    Directory of Open Access Journals (Sweden)

    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 

  7. Nonvisual ganglion cells, circuits and nonvisual pigments

    Institute of Scientific and Technical Information of China (English)

    Ali Akbar Kashani; WANG Huai-zhou; WANG Ning-li

    2009-01-01

    @@ To the editor: WANG and his colleagues provided the evidence that "both melanopsin-containing and superior collicular retinal ganglion cells were damaged by chronic ocular hypertension, indicating that glaucomatous neural degeneration involves the non-image-forming visual pathway".

  8. 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

    Directory of Open Access Journals (Sweden)

    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.

  9. Comparative Diagnostic Accuracy of Ganglion Cell-Inner Plexiform and Retinal Nerve Fiber Layer Thickness Measures by Cirrus and Spectralis Optical Coherence Tomography in Relapsing-Remitting Multiple Sclerosis

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    Julio J. González-López

    2014-01-01

    Full Text Available Objective. To estimate sensitivity and specificity of several optical coherence tomography (OCT measurements for detecting retinal thickness changes in patients with relapsing-remitting multiple sclerosis (RRMS, such as macular ganglion cell-inner plexiform layer (GCIPL thickness measured with Cirrus (OCT and peripapillary retinal nerve fiber layer (pRNFL thickness measured with Cirrus and Spectralis OCT. Methods. Seventy patients (140 eyes with RRMS and seventy matched healthy subjects underwent pRNFL and GCIPL thickness analysis using Cirrus OCT and pRNFL using Spectralis OCT. A prospective, cross-sectional evaluation of sensitivities and specificities was performed using latent class analysis due to the absence of a gold standard. Results. GCIPL measures had higher sensitivity and specificity than temporal pRNFL measures obtained with both OCT devices. Average GCIPL thickness was significantly more sensitive than temporal pRNFL by Cirrus (96.34% versus 58.41% and minimum GCIPL thickness was significantly more sensitive than temporal pRNFL by Spectralis (96.41% versus 69.69%. Generalised estimating equation analysis revealed that age (P=0.030, optic neuritis antecedent (P=0.001, and disease duration (P=0.002 were significantly associated with abnormal results in average GCIPL thickness. Conclusion. Average and minimum GCIPL measurements had significantly better sensitivity to detect retinal thickness changes in RRMS than temporal pRNFL thickness measured by Cirrus and Spectralis OCT, respectively.

  10. Modulation of cannabinoid to GABA currents in retinal ganglion cells in human and mice%大麻素对人和小鼠视网膜神经节细胞GABA电流的调控差异

    Institute of Scientific and Technical Information of China (English)

    罗雪; 刘诗亮; 江梦南; 沈雨濛; 胡单萍; 沈吟

    2015-01-01

    目的 比较人和小鼠视网膜内源性大麻素类受体1(cannabinoid receptor,CB1)的表达差异,观察大麻素受体激动剂WIN55212-2对不同种属视网膜神经节细胞GABA电流的调控作用.方法 采用冰冻切片免疫荧光染色,观察CB1受体在视网膜中的表达.制备视网膜薄片,行全细胞膜片钳记录.在神经节细胞上给予100 μmol/L GABA快速加药诱导出电流I GABA,而后观察孵育大麻素受体激动剂WIN55212-2时GABA诱导的IGABA及同时孵育WIN 55212-2和大麻素受体拮抗剂SR141716A的电流IGABA.结果 人和小鼠视网膜CB1受体的分布有所不同,人的内核层、外核层、神经节细胞层有显著的CB1表达,但小鼠CB1受体主要表达在内网状层、外网状层上;膜片钳结果显示不管是在人还是在小鼠的视网膜上,孵育WIN55212-2后的GABA诱导电流幅度均有显著减小.不同的是,在人视网膜神经节细胞上,WIN55212-2明显减慢了GABA电流的反应速度,表现在电流达峰时间明显延长,恢复时间缩短(P<0.05).WIN55212-2对小鼠视网膜神经节细胞GABA的反应速度无明显差别(P>0.05).结论 CB1受体在人和小鼠视网膜中有差异性分布,对神经节细胞的GABA电流影响也不同.孵育WIN55212-2可抑制人和小鼠神经节细胞GABA电流幅度,但仅对人的神经节细胞的GABA电流的动力学速度有影响.%Objective To compare the expression of endogenous cannabinoid receptor 1 (CB1) in human and mouse retinal ganglion cells and observe the modulation of CB1 receptor agonist WIN55212-2 to γ-aminobutyric acid (GABA) currents.Methods Immunofluorescence assay was applied to study the expression pattern of CB1 receptors in the retina.Whole-cell patch-clamp technology was used to record GABA currents in the retinal ganglion cells after applying 2 μmol/L WIN55212-2 or 2 μmol/L WIN55212-2 + 4 μmol/L SR141716A (CB1 receptor antagonist).Results CB1 receptors were expressed in the human outer nuclear

  11. Retinal research using the perfused mammalian eye.

    Science.gov (United States)

    Niemeyer, G

    2001-05-01

    The effort to isolate and maintain alive in vitro an intact mammalian eye is rewarded by the full control provided over the arterial input and exclusion of systemic regulatory or compensatory mechanisms. Electrical recording of typical light-evoked field potentials from retina and optic nerve can be complemented by single-cell recording. Thus, light-induced electrical activity reflects the function of the retinal pigment epithelium, of the layers of the retina and of the ganglion cells or their axons. Retinal function in vitro is documented by electrophysiological and morphological methods revealing subtle features of retinal information processing as well as optic nerve signals that approach-at threshold stimulus intensity-the human psychophysical threshold. Such sensitivity of third-order retinal neurons is described for the first time. This well controlled in vitro preparation has been used successfully for biophysical, metabolic and pharmacological studies. Examples are provided that demonstrate the marked sensibility of the rod system to changes in glucose supply. Moreover, histochemical identification of glycogen stores revealed labeling of the second- and third-order neurons subserving the rod system, in addition to labeling of Müller (glial) cells in the cat retina. The glycogen content of the cat retina is augmented by prolonged anesthesia, largely depleted by ischemia after enucleation and enhanced by insulin. Pharmacological experiments using agonists and antagonists of putative retinal neurotransmitters are summarized and outlined using the muscarinic cholinergic agonist QNB as an example. Actions and uptake of the neuromodulator adenosine are presented in detail, including inhibitory effects on physiologically characterized ganglion cells. Neuronal effects of adenosine are distinguished from those resulting from vasodilatation and from glycogenolysis induced by the neuromodulator. To open the blood-retina barrier, a hyperosmotic challenge can be

  12. Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75NTR-mediated axon guidance

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    Broom Emma R

    2010-11-01

    Full Text Available Abstract Background Retinotectal map formation develops via topographically specific guidance and branching of retinal axons in their target area. This process is controlled, in part, by reverse signalling of ephrinAs expressed on retinal axons. As glycosylphosphatidylinositol-anchored molecules, ephrinAs require transmembrane co-receptors to exert this function, for which the two neurotrophin receptors, p75NTR and TrkB, were recently proposed. Results We show here that the ligands for these receptors, the brain-derived neurotrophic factor precursor (proBDNF and its processed form, BDNF, respectively, control the branching of retinal axons antagonistically, which they mediate by inducing the corresponding neurotrophin receptor-ephrinA complexes. Moreover, scavenging proneurotrophins, by adding antibodies specific for the pro-domain of proBNDF or a soluble extracellular domain of p75NTR, abolish repellent ephrinA reverse signalling in the stripe assay. Conclusions This indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75NTR interaction and enabling repellent axon guidance. The antagonistic functions of proBDNF and BDNF raise the possibility that topographic branching is controlled by local control of processing of proneurotrophins.

  13. 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…

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. Repeatability of Perimacular Ganglion Cell Complex Analysis with Spectral-Domain Optical Coherence Tomography

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    Dorothy S. K. Ng

    2015-01-01

    Full Text Available Purpose. To assess the repeatability of spectral-domain optical coherence tomography to measure macular and perimacular ganglion cell complex thicknesses and compare retinal ganglion cell parameters between algorithms. Methods. Ninety-two nonglaucomatous eyes from 92 participants underwent macular and perimacular ganglion cell complex thickness measurement using OCT-HS100 Glaucoma 3D algorithm and these measurements were repeated for 34 subjects. All subjects also had macular ganglion cell-inner plexiform layer thickness measured by Cirrus HD-OCT Ganglion Cell Analysis algorithm. Intraclass correlation coefficient and Pearson’s correlation analyses were performed. Results. Subfields of both macular and perimacular ganglion cell complex thicknesses had high intraclass correlation coefficient values between 0.979 (95% confidence interval [CI]: 0.958–0.989 and 0.981 (95% CI: 0.963, 0.991 and between 0.70 (95% CI: 0.481–0.838 and 0.987 (95% CI: 0.956–0.989, respectively. The overall average ganglion cell complex and macular average ganglion cell-inner plexiform layer thicknesses were strongly correlated (r=0.83, P<0.001.  Conclusions. The assessment of macular and perimacular retinal ganglion cell parameters by OCT-HS100 Glaucoma 3D algorithm is highly repeatable, and strongly correlates to retinal ganglion cell parameters assessed by Ganglion Cell Analysis algorithm. A comprehensive evaluation of retinal ganglion cells may be possible with OCT-HS100.

  16. Repeatability of Perimacular Ganglion Cell Complex Analysis with Spectral-Domain Optical Coherence Tomography

    OpenAIRE

    Ng, Dorothy S. K.; Preeti Gupta; Yih Chung Tham; Chye Fong Peck; Tien Yin Wong; Mohammad Kamran Ikram; Cheung, Carol Y.

    2015-01-01

    Purpose. To assess the repeatability of spectral-domain optical coherence tomography to measure macular and perimacular ganglion cell complex thicknesses and compare retinal ganglion cell parameters between algorithms. Methods. Ninety-two nonglaucomatous eyes from 92 participants underwent macular and perimacular ganglion cell complex thickness measurement using OCT-HS100 Glaucoma 3D algorithm and these measurements were repeated for 34 subjects. All subjects also had macular ganglion cell-in...

  17. Dose-dependent and combined effects of N-methyl- D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine on the survival of retinal ganglion cells in adult hamsters

    Institute of Scientific and Technical Information of China (English)

    Yaoyu Li; An'an Yang; Tingting Zhu; Zhao Liu; Siwei You; Kwok-Fai So

    2012-01-01

    This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine (L-NA) on the survival of retinal ganglion cells (RGCs) at 1 and 2 weeks after unilateral optic nerve transection in adult hamsters. The left optic nerves of all animals were transected intraorbitally 1 mm from the optic disc and RGCs were retrogradely labeled with Fluorogold before they received different daily dosages of single MK-801 or L-NA as well as daily combinational treatments of these two chemicals. All experimental and control animals survived for 1 or 2 weeks after optic nerve transection. Our results revealed that the mean numbers of surviving RGCs increased and then decreased when the dosage of MK-801 (1.0, 3.0 and 4.5 mg/kg) and L-NA (1.5, 3.0, 4.5 and 6.0 mg/kg) increased at both 1 and 2 weeks survival time points. Daily combinational use of 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA lead to a highest RGC number that was even higher than the sum of the RGC numbers in 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA subgroups at 2 weeks. These findings indicated that both MK-801 and L-NA can protect axotomized RGCs in a dose-dependent manner and combinational treatment of these chemicals possesses a potentiative and protective effect.

  18. Notch信号通路抑制剂调控鼠Müller细胞来源的干细胞向神经节细胞分化的研究%Notch signaling pathway inhibitor promotes differentiation of Müller cell-derived retinal stem cells into retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    宋伟涛; 张雪咏; 熊思齐; 蒋剑; 文丹; 喻一心; 夏晓波

    2014-01-01

    Objective To observe the role of Notch signaling pathway inhibitor in differentiationprocess of stem cells derived from retinal Müller cells into the ganglion cell.Methods Retinas of Sprague Dawley rat at postnatal 10-20 days were dissociated from eye balls.The third passage of Müller cells was used in this experiment,which cultured by repeated incomplete pancreatic enzyme digestion method.The retinal Müller cells were induced in the serum-free dedifferentiation medium.The cell proliferation state was observed under an inverted microscope.The expression of the specific markers Nestin and Ki-67 of retinal stem cells was measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.The positive rate of nucleus was detected by Edu.The retinal stem cells was divided into Gamma secretase inhibtor-Ⅰ (GSI) group and control group,the rate of ganglion cells was counted by using immunofluorescence staining.Results The cell proliferation had gathered to form a sphere.Immunofluorescence staining showed that the expressions of Nestin and Ki-67 were (92.94 ± 6.48%) and (85.96±6.04%) respectively.Edu positive rate of nucleus was (82.80±6.65)%.RT-PCR and Western blot further confirmed the high expression of Nestin and Ki-67 in the cell spheres but not in the Müller cells.The positive rate of ganglion cells were (16.98±2.87)% and (11.17±0.71)% in GSI group and control group respectively,with the significant difference (t =3.210,P =0.002).Conclusion Notch signaling pathway is an important regulatory gene in stem cells differentiated into retinal ganglion cell.%目的 观察Notch信号通路抑制剂对鼠Müller细胞来源的视网膜干细胞的调控作用.方法 Sprague Dawley大鼠20只,鼠龄10~20 d.显微镜下分离视网膜,采用反复不完全胰蛋白酶消化法传代培养.取传代3次的细胞用于实验.Müller细胞诱导去分化,荧光显微镜下观察细胞增生状态,免疫荧光细胞化学染色,

  19. Repeatability of Perimacular Ganglion Cell Complex Analysis with Spectral-Domain Optical Coherence Tomography.

    Science.gov (United States)

    Ng, Dorothy S K; Gupta, Preeti; Tham, Yih Chung; Peck, Chye Fong; Wong, Tien Yin; Ikram, Mohammad Kamran; Cheung, Carol Y

    2015-01-01

    Purpose. To assess the repeatability of spectral-domain optical coherence tomography to measure macular and perimacular ganglion cell complex thicknesses and compare retinal ganglion cell parameters between algorithms. Methods. Ninety-two nonglaucomatous eyes from 92 participants underwent macular and perimacular ganglion cell complex thickness measurement using OCT-HS100 Glaucoma 3D algorithm and these measurements were repeated for 34 subjects. All subjects also had macular ganglion cell-inner plexiform layer thickness measured by Cirrus HD-OCT Ganglion Cell Analysis algorithm. Intraclass correlation coefficient and Pearson's correlation analyses were performed. Results. Subfields of both macular and perimacular ganglion cell complex thicknesses had high intraclass correlation coefficient values between 0.979 (95% confidence interval [CI]: 0.958-0.989) and 0.981 (95% CI: 0.963, 0.991) and between 0.70 (95% CI: 0.481-0.838) and 0.987 (95% CI: 0.956-0.989), respectively. The overall average ganglion cell complex and macular average ganglion cell-inner plexiform layer thicknesses were strongly correlated (r = 0.83,  P HS100 Glaucoma 3D algorithm is highly repeatable, and strongly correlates to retinal ganglion cell parameters assessed by Ganglion Cell Analysis algorithm. A comprehensive evaluation of retinal ganglion cells may be possible with OCT-HS100.

  20. A review of the pharmacology of carbonic anhydrase inhibitors for the treatment of glaucoma in dogs and cats.

    Science.gov (United States)

    Maślanka, Tomasz

    2015-03-01

    Glaucoma is a heterogeneous group of disorders usually associated with elevated intraocular pressure (IOP), leading to optic nerve damage, retinal ganglion cell death and irreversible vision loss. Therefore, medications that lower IOP are the mainstay of glaucoma therapy. Carbonic anhydrase inhibitors (CAIs) are some of the principal drugs used in the management of canine and feline glaucoma. This paper summarises current knowledge of the mechanism of action of these agents and their effect on IOP in dogs and cats. It also discusses potential harmful side effects of CAIs and presents current opinions about their role and place in the medical management of glaucoma in small animals.

  1. Excessive retinal ganglion cell loss after optic nerve crushed with forceps in rats%钳夹法造成大鼠视网膜神经节细胞过量丢失

    Institute of Scientific and Technical Information of China (English)

    廖良; 徐铭谦; 韦企平; 周剑; 孔莹莹; 孙艳红

    2011-01-01

    Objective To evaluate the injury degree of retinal ganglion cells (RGCs) after optic nerve crushed with forceps. Methods A total of 38 male Wistar rats were divided into forceps groups, which was subdivided into group A to group E, with crushing time of 12 seconds,9 seconds,6 seconds,3 seconds and 1 second, the group F was the forceps group at reverse direction,5 rats in each group. The optic nerve at temple side of rat eyeball was exposed. Optic nerves at 2 mm behind the eyeball were crushed with 90 g micro forceps and then with the 40 g forceps at reverse direction. Left eye of each rat was taken operation, and right eye was treated as normal control. Left eyes of rats in shame operation group were taken treatment to expose optic nerve behind the eyeball,but not with crush. Amount and survival rate of RGCs were calculated with fluorogold regressive labeling RGCs and retinal stretched preparation. Results Cell densities of left and right eyes of rats in shame operation group were (2 679 ± 67) mm-2 and(2 689 ±53)mm-2,there was no significant difference(P = 0. 8%) ,and were (220±167)mm-2,(265 ±232)mm-2, (298 ±239)mm-2, (478 ±682)mm -2, (769 ±615) mm-2 and (974 ±476) mm-2 in forceps groups, which were obviously decreased. There was negative correlation between impulse of forceps(force of forceps multiply time) and survival rate of RGCs. Conclusions Crush with forceps can make definite and quantitative optic injury,but the injury is serious and stability is poor. There is still a marked gap between our experiment and the actual pathogenesis of traumatic optic neuropathy.%目的 评估钳夹视神经对视网膜神经节细胞(retinal ganglion cells,RGCs)的损伤程度.方法 取38只雄性Wistar大鼠,夹持组(n=30)按夹持时间12 s、9 s、6 s,3 s、1 s分为A-E组,F为反身夹持组,每组各5只大鼠.沿大鼠眼球颞侧暴露视神经,于球后2 mm处用90 g微型视神经夹夹持视神经,另有40 g反向镊在球后2 mm处夹持视神经,每

  2. Inhibition on Apoptosis Induced by Elevated Hydrostatic Pressure in Retinal Ganglion Cell-5 via Laminin Upregulating β1-integrin/Focal Adhesion Kinase/Protein Kinase B Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    Yi Li; Yan-Ming Chen; Ming-Ming Sun; Xiao-Dan Guo; Ya-Chen Wang; Zhong-Zhi Zhang

    2016-01-01

    Background:Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells (RGCs).High intraocular pressure (HIOP),the main risk factor,causes the optic nerve damage.However,the precise mechanism of HIOP-induced RGC death is not yet completely understood.This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures,explore whether laminin is associated with apoptosis under pressure,whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival.Methods:RGC-5 cells were exposed to 0,20,40,and 60 mmHg in a pressurized incubator for 6,12,and 24 h,respectively.The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,and Western blotting of cleaved caspase-3 protein.Location and expression oflaminin were detected by immunofluorescence.The expression of β 1-integrin,phosphorylation of focal adhesion kinase (FAK) and protein kinase B (PKB,or AKT) were investigated with real-time polymerase chain reaction and Western blotting analysis.Results:Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells.Pressure with 40 mmHg for 24 h induced a maximum apoptosis.Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h.After pretreating with laminin,RGC-5 cells survived from elevated pressure.Furthermore,β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group.Conclusions:The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure.Laminin can protect RGC-5 cells against high pressure via β 1-integrin/FAK/AKT signaling pathway.These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure,and laminin or activating β1

  3. Fetal bovine serum induction differentiation of retinal stem cells into retinal ganglion-like cells in vitro%胎牛血清传代培养诱导新生大鼠视网膜干细胞向视网膜神经节样细胞分化的研究

    Institute of Scientific and Technical Information of China (English)

    张慧; 董方田

    2015-01-01

    Objective To investigate the ability of 10%fetal bovine serum ( FBS) to induce the differentiation of retinal stem cells ( RSCs ) derived from new born rats into retinal ganglion-like cells in vitro.Method Mixed retinal cells were isolated from post-natal day 5 rats and cultured to passage 5 in flasks in DMEM/F12 medium supplemented with 10%FBS.Protein and mRNA levels of markers specific for RSCs (Nestin and Masushi) and retinal ganglion cells (Thy-1) in both freshly isolated mixed retinal cells and cultured cells at passage 5 were determined by immunofluorescence and RT-PCR respectively. Result After the initial culture for 24 h, a small proportion of mixed retinal cells became adherent and elongated while the majority of the cells remained unattached.At the time of the first medium change at 48 h, cells displayed a short spindle-shaped morphology with a scattered pattern of growth.At 4 days,cells displayed a typical morphology of RSCs and became colonized.At days 7-10,cells grew to a confluentmonolayer and were sub-cultured.At 12 h after sub-culture,cells became bipolarized and had a long spindleshapedmorphology with emerging branches at the end of the spindle.At passage 3, cells underwentexponential growth.By passage 5,the morphology of the cells became uniform and cell growth was sloweddown.High protein and mRNA levels of stem cell markers Nestin and Masuhi but low protein and mRNAlevels of ganglion cell mark Thy-1 were detected in freshly isolated mixed cells.In contrast,Nestin andMasuhi protein and mRNA levels were significantly increased but Thy-1 protein and mRNA levels weresignificantly reduced in passage 5 cells as compared with the initial cell preparations ( P <0.05). Conclusion There remain RSCs in PN5 Stem cells are present in post-natal rat retina cells.Continuouspassaging in medium containing 10% FBS may induce differentiation of these stem cells into retinal ganglioncells in vitro.%目的:探讨胎牛血清( FBS)传代培养诱导新生大

  4. Overexpression of Heme Oxygenase-1 in Mesenchymal Stem Cells Augments Their Protection on Retinal Cells In Vitro and Attenuates Retinal Ischemia/Reperfusion Injury In Vivo against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Li Li

    2017-01-01

    Full Text Available Retinal ischemia/reperfusion (I/R injury, involving several ocular diseases, seriously threatens human ocular health, mainly treated by attenuating I/R-induced oxidative stress. Currently, mesenchymal stem cells (MSCs could restore I/R-injured retina through paracrine secretion. Additionally, heme oxygenase-1 (HO-1 could ameliorate oxidative stress and thus retinal apoptosis, but the expression of HO-1 in MSC is limited. Here, we hypothesized that overexpression of HO-1 in MSC (MSC-HO-1 may significantly improve their retina-protective potentials. The overexpression of HO-1 in MSC was achieved by lentivirus transduction. Then, MSC or MSC-HO-1 was cocultured with retinal ganglion cells (RGC-5 in H2O2-simulated oxidative condition and their protection on RGC-5 was systemically valuated in vitro. Compared with MSC, MSC-HO-1 significantly attenuated H2O2-induced injury of RGC-5, including decrease in cellular ROS level and apoptosis, activation of antiapoptotic proteins p-Akt and Bcl-2, and blockage of proapoptotic proteins cleaved caspase 3 and Bax. In retinal I/R rats model, compared with control MSC, MSC-HO-1-treated retina significantly retrieved its structural thickness, reduced cell apoptosis, markedly attenuated retinal oxidative stress level, and largely regained the activities of typical antioxidant enzymes, SOD and CAT. Therefore, it could be concluded that overexpression of HO-1 provides a promising strategy to enhance the MSC-based therapy for I/R-related retinal injury.

  5. 早期糖尿病大鼠视网膜神经节细胞树突形态异常的研究%Study on abnormal dendrite of retinal ganglion cells in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    徐格致; 秦要武; 王文吉

    2008-01-01

    Objective To observe the morphological changes of dendrite and soma in retinal ganglion cells (RGCs) which subsisted in early diabetic rats. Methods The RGCs of 3-months-course diabetic rats and coeval normal rats were marked by gene gun techniques. To collect RGCs photographs by Leica microscope with Z axis and CCD camera;to observe the changes of diameter, variance of structural features in dendritic field and somata after classification which according to the size and morphology. Thy-1 antibody marks on the retinal RGCs, taking a photograph under fluorescent microscope, counting the changes of retinal RGCs density in early diabetic rat. Results In three-month diabetic rats, the density of retinal RGCs was decreased obviously. Morphological changes of RGCs in the dendritic fields were observed with gene gun technique. There was no severe variation in all kinds of the bole of cell dendrite,in which some only showed crispation partially and sparseness also twisting in the dendritic ramus. The mean diameter of dendritic field and soma in class A of diabetic rats was (401±86)μm, the mean diameter of dendritic field in control group was (315±72) μm,compared with each other, there is statistically significant differences (t=21. 249, P0.05); the mean diameter of dendritic field and soma in class B of diabetic rats were (170±36). (14±2) μm respectively, in control group were (165±36), (16±2) μm, the mean diameter of dendritic field and soma in class C of diabetic group were (265±78),(17±5) μm respectively, in control group were (251±57),(17±4) μm , compared with each other,there are on statistically significant differences (t=1.357,0.798,0. 835,1.104 ,P>0.05). ConclusionsIn short-term diabetes, the survived RGCs show good plasticity in adult diabetic rats, especially in class A. The changes of dendrites were more sensitive than the soma, which could be the leading index of themorphologic changes of RGCs in the early stage. The good plasticity showed by

  6. 霍乱毒素对金黄地鼠视网膜节细胞再生的作用%THE EFFECTS OF CHOLERAL TOXIN ON THE REGENERATION OF THE RETINAL GANGLION CELLS IN GOLDEN HAMSTER

    Institute of Scientific and Technical Information of China (English)

    李雯; 李海标

    2001-01-01

    Objective The present study was aimed at investigating theeffects of cholera toxin(CTx) on promoting the regeneration of retinal ganglion cells(RGCs) in hamster retina. Methods After optic nerve (ON) tran section, an autologus sciatic nerve (attached graft, AG) was removed and sutured to the proximal stump of the ON. CTX was injected or (and) a small segment of sciatic nerve (SN) inserted intravitrously. Animals were separated into 5 group s:regenerating control group(AG groups and solution groups); AG+CTX groups; AG + SN groups; AG+CTX+SN groups; Effect and Dosage groups; Animals in the former 4 groups were allowed to survive for 2-6 weeks respectively. The regenerated RGC s were labeled retrogradely by granular blue, and the changes in number of rege nerating RGCs in each retina were observed under fluorescent microscope. Results The mean numbers of regenerating RGCs in AG+CTX groups were inc reased and significantly higher than those in AG groups and solution groups at e ach time point(P<0.05). Similar results were obtained in AG+SN groups; In AG+CTX+SN groups, the mean number of regenerating RGCs was markedly increa sed than those in the AG groups and AG+SN groups at each time point (P<0.01 ). Conclusion Our results indicated that injection of CTX or/and insertion of SN intravitrously could enhance the regeneration of the axotomized RGCs significantly.%目的 探讨霍乱毒素(CTX)对金黄地鼠视网膜节细胞(RGCs)再生的促进作用。 方法 成年金黄地鼠近端切断视神经(ON)并缝接一段自体坐骨神经(AG),玻璃体内注射CTX及/或插入小段坐骨神经分支(SN)。动物随机分为AG组和溶剂组;AG+CTX组;AG+SN组;AG+CTX+SN组;量效关系组。前4组动物存活2~6周。用粒蓝逆行标记再生的RGCs,在荧光镜下观察视网膜平铺片再生RGCs的数量变化。 结果 AG+CTX组各时间点视网膜再生RGCs平均数比AG组和溶剂组增加,具有统计学意义(P<0.05);AG+SN组也得出相似

  7. 白细胞介素-6对视网膜神经节细胞保护作用的研究进展%Research progress of interleukin-6 playing neuroprotective effects on retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    吕红丽

    2015-01-01

    目前,青光眼的发病机制仍未明确,眼压升高、缺血、神经营养因子的剥夺、胶质细胞的激活、谷氨酸兴奋性反应等多种机制均可以促进青光眼性视网膜神经节细胞(RGCs)凋亡.通过干预神经细胞的凋亡途径从而防止RGCs损伤已经成为青光眼视神经保护治疗的重点.近年来研究表明,胶质细胞分泌的白细胞介素-6(IL-6)和睫状神经营养因子(CNTF)具有同样的作用,即在视神经损伤和眼内炎症刺激后,可促进轴突生长,提高RGCs的存活率.视网膜在视神经损伤或眼内炎症刺激后可表达IL-6,IL-6与RGCs上的IL-6受体结合后,通过JAK/STAT3和PI3K/Akt/mTOR 2种途径,增加热休克蛋白(HSPs)的表达,解除抑制性髓磷脂基质对受损神经轴突再生的抑制作用,抵抗凋亡因子肿瘤坏死因子-α(TNF-α)和NO的作用,并刺激再生相关基因Sprr1a和Gap-43的表达,从而发挥其对RGCs的保护作用.本文就IL-6对RGCs保护作用的相关研究进展进行综述.%Recently, the risk factors for glaucoma is not very clear, a variety of mechanisms, such as increased intraocular pressure,ischemia,deprivation of neurotrophic factors, glial cells activation, glutamate excitatory reactions can promote glaucomatous retinal ganglion cells (RGCs) apoptosis.Through the intervention of nerve cells apoptosis pathway to prevent RGCs damage has become the focus of treatment of glaucoma optic protection.In recent years, studies have shown that interleukin-6 (IL-6) secreted by astrocytes and microglia has the same effect with ciliary neurotrophic factor (CNTF), which can stimulate axon growth and improve the survival rate of RGCs after optic nerve injury and intraocular inflammation.Optic nerve injury and inflammation can induce the expression of IL-6 in retina.IL-6 binds to its receptor expressed in RGCs, activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway that up-regulates expression of

  8. Cholera toxin and pregnancy promote regeneration of the retinal ganglion cells in golden hamster%霍乱毒素及妊娠对金黄地鼠视网膜节细胞再生的作用

    Institute of Scientific and Technical Information of China (English)

    李飞; 黄锦桃; 李海标

    2011-01-01

    目的:观察霍乱毒素(CTx)及妊娠对成年金黄地鼠视神经扎断后视网膜节细胞(RGCs)轴突再生的促进作用.方法:确定成年金黄地鼠交配3d后,扎断视神经(ON)近端,玻璃体内注射CTx.动物随机分为实验组和对照组:对照组为单纯扎断ON为损伤组、损伤PBS组;实验组分为CTx组与妊娠后扎断ON妊娠损伤组与妊娠CTx组.术后动物存活3周.用荧光金逆行标记再生的视网膜节细胞( RGCs),在荧光镜下观察视网膜平铺片再生RGCs的数量变化,并比较实验组各组再生RGCs的周长.结果:CTx组、妊娠损伤组、妊娠CTx组视网膜再生RGCs平均数比损伤组及PBS组增加,差异具有统计学意义.妊娠CTx组比CTx组、妊娠损伤组视网膜再生RGCs平均数增加.实验组各组再生的RGCs周长相比差异无统计学意义.结论:妊娠及玻璃体注入CTx具有促进视神经扎断后视网膜节细胞轴突再生的作用,两者有协同作用,各组再生的RGCs大小无明显差别.%Objective: To investigate the effects of cholera toxin (CTx) and pregnancy on promoting the axon regeneration of retinal ganglion cells (RGCs) in hamster retina. Methods: In day 3 after golden hamster mating, optic nerve (ON) micro-crushed, CTx was injected intravitrously. The rats were separated into a regenerating control group (injuried group and in-juried+PBS group) and an experiment group (injuried+CTx group, pregnancy + injuried group, pregnancy+injuried+CTx group). The rats in each group were allowed to survive for 3 weeks. The regenerating RGCs were labeled retrogradely with fluorogold, and changes in number of regenerating RGCs in each retina were observed under a fluorescence microscope. The circumference of regenerating RGCs in each experimental group was compared. Results: The mean numbers of regenerating RGCs in the injuried+CTx group, pregnancy + injuried group and pregnancy+injuried+CTx group were increased and significantly higher than those in the

  9. Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration

    OpenAIRE

    2009-01-01

    Retinal implants are intended to help patients with degenerative conditions by electrically stimulating surviving cells to produce artificial vision. However, little is known about how individual retinal ganglion cells respond to direct electrical stimulation in degenerating retina. Here we used a transgenic rat model to characterize ganglion cell responses to light and electrical stimulation during photoreceptor degeneration. Retinas from pigmented P23H-1 rats were compared with wild-type re...

  10. 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.

  11. Fractal features of dark, maintained, and driven neural discharges in the cat visual system

    CERN Document Server

    Lowen, S B; Kaplan, E; Saleh, B E A; Teich, M C; Lowen, Steven B.; Ozaki, Tsuyoshi; Kaplan, Ehud; Saleh, Bahaa E. A.; Teich, Malvin C.

    1999-01-01

    We employ a number of statistical measures to characterize neural discharge activity in cat retinal ganglion cells (RGCs) and in their target lateral geniculate nucleus (LGN) neurons under various stimulus conditions, and we develop a new measure to examine correlations in fractal activity between spike-train pairs. In the absence of stimulation (i.e., in the dark), RGC and LGN discharges exhibit similar properties. The presentation of a constant, uniform luminance to the eye reduces the fractal fluctuations in the RGC maintained discharge but enhances them in the target LGN discharge, so that neural activity in the pair no longer mirror each other. A drifting-grating stimulus yields RGC and LGN driven spike trains similar in character to those observed in the maintained discharge, with two notable distinctions: action potentials are reorganized along the time axis so that they occur only during certain phases of the stimulus waveform, and fractal activity is suppressed. Under both uniform-luminance and drift...

  12. Ganglion cell size and distribution in the retina of the two-toed sloth (Choloepus didactylus L.).

    Science.gov (United States)

    Andrade-da-Costa, B L; Pessoa, V F; Bousfield, J D; Clarke, R J

    1989-01-01

    The distribution of ganglion cell densities and sizes was studied in Nissl-stained flat-mount retinae of the two-toed sloth. The area centralis, a weak specialization with low ganglion cell density, is located in the temporal retina close to the center of the eye. The presence of a visual streak was noted. The distribution of different ganglion cell sizes was approximately equal throughout the retina. Although the retinal organization differs from that of the closely related three-toed sloth, the presumed function of retinal specializations in both species is to guide limb movements by permitting visualization of the branch along which the animal is climbing.

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

    Science.gov (United States)

    Chen, Yin-Peng; Chiao, Chuan-Chin

    2014-01-01

    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.

  14. Patterned electrical stimulation of primate retina for the development of retinal prostheses

    OpenAIRE

    2012-01-01

    Epiretinal prostheses are designed to restore vision to people blinded by retinal degenerations, using electrical stimulation with an array of electrodes implanted on the surface of the retina to convey artificial visual signals to the brain. Current clinical prostheses provide limited visual function, in part because the activity that they generate is different from natural retinal responses to visual stimuli. An ideal retinal prosthesis would stimulate the retinal ganglion cells (RGCs) in a...

  15. Ganglion cell death in glaucoma: from mice to men.

    Science.gov (United States)

    Nickells, Robert W

    2007-01-01

    Glaucoma results from the degeneration of retinal ganglion cells and their axons. Over the last 20 years several important advancements have been made in our understanding of the molecular pathology of this disease, particularly through the development of rat models of experimental glaucoma and the characterization of a spontaneous secondary form of glaucoma in DBA/2 substrains of inbred mice. One of these advances is the observation that ganglion cells die by apoptosis, an intrinsic molecular pathway of programmed cell death. An important aspect of this cell death process is the concept that these cells actually undergo compartmentalized self-destruction. Importantly, genetic evidence now suggests that axons die independently of the apoptotic program that executes the cell body or soma. This review briefly summarizes some of the most significant developments in glaucoma research, with respect to the process of ganglion cell degeneration.

  16. Focal Electrical Stimulation of Major Ganglion Cell Types in the Primate Retina for the Design of Visual Prostheses

    OpenAIRE

    2013-01-01

    Electrical stimulation of retinal neurons with an advanced retinal prosthesis may eventually provide high-resolution artificial vision to the blind. However, the success of future prostheses depends on the ability to activate the major parallel visual pathways of the human visual system. Electrical stimulation of the five numerically dominant retinal ganglion cell types was investigated by simultaneous stimulation and recording in isolated peripheral primate (Macaca sp.) retina using multi-el...

  17. Study on the differentiation of retinal ganglion cells from rat Müller cells in vitro%体外诱导大鼠视网膜Müller细胞向神经节细胞定向分化的研究

    Institute of Scientific and Technical Information of China (English)

    曾琦; 夏晓波

    2010-01-01

    Objective To certify the ability of retinal Müller cells for producing neural stem cells in vitro and to find a method that can aquire more retinal ganglion cells from these stem cells. Methods Müller cells were isolated from rat retina, and proliferating cells were expanded in serum-containing medium. The third or fourth passage of cells were identified by RT-PCR and Immunocytochemistry analysis. For dedifferentiation, the cultured cells were transferred to the sphere-culture medium composed of DMEM/F-12 supplemented with N2,bFGF and EGF. After 3-5 days, the culture media were substituted with BDNF,RA and 5% FBS and culture was continued for 7-10 days. At last, cells in this two stages were identified by immunocytochemical analysis. Results Approximately (95. 17 ±2. 68)% of cells in the culture were Miiller cells as revealed by expressing glutamate-spartate transporters (GLAST) and glutamine synthetase ( GS) immunoreactivities. RT-PCR analysis also revealed that the culture was enriched for Müller cells and not contaminated with other retinal cells. After 3-5 days cultured in the the sphere-culture medium, the Mttller cells became round and differentiate to neurospheres. (95. 26 ± 1. 35)% of cells in the neurosphere were positively reacted for Nestin,and (90. 33 ±4. 12)% for BrdU. Neurospheres cultured for 7-10 days with 5% FBS,BDNF and RA can redifferentiate to various new cells. And the expression of Thyl. 1 which is a marker of retinal ganglion cells was observed in (21. 14 ± 1. 49)% of these cells. Conclusions Adult rodent Müller cells can generate clonal neurospheres,which consist of proliferating and multipotent cells,and redifferentiate to ganglion cells. This study may provide a novel tool in the study on stem cells and contribute to therapies for neural regeneration in retina.%目的 研究鼠视网膜Müller细胞经体外条件培养基诱导后去分化为神经干细胞及进一步定向分化成神经节样细胞的特性.方法 实

  18. Intravitreal injection of erythropoietin sustained-release microspheres protects damaged retinal ganglion cells in rats%促红细胞生成素缓释微球玻璃体腔注射对视网膜神经节细胞的保护作用

    Institute of Scientific and Technical Information of China (English)

    荣先芳; 莫晓芬; 任甜甜; 袁伟恩; 王艳; 王鑫

    2010-01-01

    目的 探讨乳酸/羟基乙酸共聚物(PLGA)装载的促红细胞生成素(EPO)缓释微球(EPO-PLGA微球)经玻璃体腔注射对大鼠视神经挫伤模型中受损视网膜神经节细胞(RGC)的保护作用.方法 选取成年SD大鼠,建立视神经挫伤模型.建模后分别经玻璃体腔内注射含10 IU EPO的PLGA微球(EPO-PLGA组)、10 IU EPO(EPO组)、5 μl空白PLGA(PLGA组)、5 μl PBS(PBS组),另设未治疗组不予玻璃体腔注药.术后5 d和2周,做视网膜切片,对各组RGC凋亡情况行TUNEL检测;术后23 d,DiI上丘逆标RGC,并于术后4周处死大鼠,视网膜铺片观察各组RGC存活情况;每组各个时间点分别处死6只SD大鼠.采用方差分析对结果进行比较.结果 TUNEL检测显示,术后5 d和2周,各组均可见TUNEL阳性细胞,其中EPO-PLGA组和EPO组TUNEL阳性细胞显著减少,其细胞凋亡率明显少于PLGA组、PBS组及未治疗组.术后4周,视网膜铺片RGC计数显示,正常SD大鼠RGC密度为(2387.7±164.9)个/mm2,未治疗组为(748.3±58.8)个/mm2,EPO-PLGA组为(1296.7±157.6)个/mm2,EPO组为(1418.5±154.9)个/mm2,PLGA组为(821.7±52.1)个/mm2,PBS组为(804.4±86.4)个/mm2;可见EPO-PLGA组和EPO组较未治疗组细胞密度显著增高,具有明显的RGC保护作用(P均<0.01),而EPO-PLGA组和EPO组间差异无统计学意义(P=0.065).结论 EPO-PLGA缓释微球与EPO具有等效的RGC保护作用,这为进一步观察EPO-PLGA缓释微球的长效神经保护作用奠定了基础.%Objective To investigate the protective effect of erythropoietin (EPO) encapsulated in poly (L-lactic-co-glycolic acid) (PLGA) microspheres on damaged retinal ganglion cell (RGC) by intravitreal injection after optic nerve crush. Methods Adult SD rats were selected to establish an optic nerve crush model. Immediately after the crush, the animals received intravitreal doses of 10 IU EPO of EPO-PLGA microspheres (EPO-PLGA group), 10 IU EPO (EPO group), blank PLGA microshperes (PLGA group), and PBS (PBS

  19. Analysis on detecting primary open angle glaucoma based on retinal nerve fiber layer and ganglion cell complex thickness%基于视网膜神经纤维层厚度及神经节细胞复合体诊断POAG的效能分析

    Institute of Scientific and Technical Information of China (English)

    许畅; 毛晓春

    2016-01-01

    目的:比较原发性开角型青光眼( primary open angle glaucoma,POAG)与正常对照组盘周视网膜神经纤维层厚度( retinal nerve fiber layer thickness,RNFL)及黄斑区神经节细胞复合体( ganglion cell complex,GCC)厚度差异,并评价盘周 RNFL 厚度及黄斑 GCC 厚度在 POAG 中的诊断价值。  方法:采用横断面研究。连续的POAG患者56例纳入研究。选择同期年龄、性别、屈光度及眼轴匹配的正常人60名60眼作为正常对照组。用RTVue-100光学相干断层扫描技术( optical coherence tomography,OCT)检测并比较POAG组及对照组盘周RNFL厚度及黄斑GCC厚度。采用受试者工作特征曲线( receiver operating characteristic curve,ROC)及ROC曲线下面积( area under curve,AUC)评价盘周 RNFL 厚度及黄斑 GCC 厚度对青光眼的诊断价值。  结果:POAG组患者盘周所有象限RNFL均薄于正常对照组,差异有统计学意义( P  结论:POAG患者盘周RNFL厚度与黄斑GCC厚度均明显变薄,变薄的盘周RNFL厚度与黄斑GCC厚度与POAG诊断存在相关性。盘周RNFL厚度与黄斑GCC厚度均有较好的诊断价值。%AIM:To investigate the peripapillary retinal nerve fiber layer ( RNFL ) thickness and the macular ganglion cell complex ( GCC ) thickness in primary open angle glaucoma ( POAG ) eyes and to compare them with normal control eyes, and to evaluate the diagnostic ability of peripapillary RNFL thickness and macular GCC thickness in POAG. ●METHODS:This was a cross-sectional study consisting of 56 POAG patients. The control group consisted of 60 normal subjects (60 eyes) were matched in terms of age, sex, diopter and axial length. The peripapillary RNFL thickness and the macular GCC thickness of POAG eyes and normal control eyes were measured and compared by RTVue-100 optical coherence tomography ( OCT ) . To assess the diagnostic utility of peripapillary RNFL thickness and macular GCC thickness in POAG, receiver operating

  20. Imaging retinal mosaics in the living eye.

    Science.gov (United States)

    Rossi, E A; Chung, M; Dubra, A; Hunter, J J; Merigan, W H; Williams, D R

    2011-03-01

    Adaptive optics imaging of cone photoreceptors has provided unique insight into the structure and function of the human visual system and has become an important tool for both basic scientists and clinicians. Recent advances in adaptive optics retinal imaging instrumentation and methodology have allowed us to expand beyond cone imaging. Multi-wavelength and fluorescence imaging methods with adaptive optics have allowed multiple retinal cell types to be imaged simultaneously. These new methods have recently revealed rod photoreceptors, retinal pigment epithelium (RPE) cells, and the smallest retinal blood vessels. Fluorescence imaging coupled with adaptive optics has been used to examine ganglion cells in living primates. Two-photon imaging combined with adaptive optics can evaluate photoreceptor function non-invasively in the living primate retina.

  1. Rac1 selective activation improves retina ganglion cell survival and regeneration

    NARCIS (Netherlands)

    Lorenzetto, E.; Ettorre, M.; Pontelli, V.; Bolomini-Vittori, M.; Bolognin, S.; Zorzan, S.; Laudanna, C.; Buffelli, M.

    2013-01-01

    In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs) do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-relate

  2. Cell type-specific bipolar cell input to ganglion cells in the mouse retina.

    Science.gov (United States)

    Neumann, S; Hüser, L; Ondreka, K; Auler, N; Haverkamp, S

    2016-03-01

    Many distinct ganglion cell types, which are the output elements of the retina, were found to encode for specific features of a visual scene such as contrast, color information or movement. The detailed composition of retinal circuits leading to this tuning of retinal ganglion cells, however, is apart from some prominent examples, largely unknown. Here we aimed to investigate if ganglion cell types in the mouse retina receive selective input from specific bipolar cell types or if they sample their synaptic input non-selectively from all bipolar cell types stratifying within their dendritic tree. To address this question we took an anatomical approach and immunolabeled retinae of two transgenic mouse lines (GFP-O and JAM-B) with markers for ribbon synapses and type 2 bipolar cells. We morphologically identified all green fluorescent protein (GFP)-expressing ganglion cell types, which co-stratified with type 2 bipolar cells and assessed the total number of bipolar input synapses and the proportion of synapses deriving from type 2 bipolar cells. Only JAM-B ganglion cells received synaptic input preferentially from bipolar cell types other than type 2 bipolar cells whereas the other analyzed ganglion cell types sampled their bipolar input most likely from all bipolar cell terminals within their dendritic arbor.

  3. Cat parasites

    OpenAIRE

    Vošická, Kristýna

    2016-01-01

    The content of this bachelor thesis describes a different variety of cat parasites. This study discovers that the most infected group of the outdoor cats due to the fact that these animals are not provided with the same care as the household pets. Those cats are usually not vaccinated, not rid of worms, no one takes care of their fur and so they tend to become a host for the parasites. There are several kinds of parasites which attack cats. Among those belong the skin parasites like a cat fle...

  4. 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

  5. 大麻素CB1受体对大鼠视网膜神经节细胞诱发动作电位的作用%Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    蒋淑霞; 李倩; 王霄汉; 李芳; 王中峰

    2013-01-01

    Activation of cannabinoid CB1 receptors (CB 1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels.The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques.The results showed that under current-clamped condition perfusing WIN55212-2 (WIN,5 μmol/L),a CB1R agonist,did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs.In the presence of cocktail synaptic blockers,including excitatory postsynaptic receptor blockers CNQX and D-APV,and inhibitory receptor blockers bicuculline and strychnine,perfusion of WIN (5 μmol/L)hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA).Phaseplane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN.However,WIN significantly decreased +dV/dtmax and-dV/dtmax of action potentials,suggestive of reduced rising and descending velocities of action potentials.The effects of WIN were reversed by co-application of SR141716,a CB1R selective antagonist.Moreover,WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked.These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.%激活大麻素CB1受体(CB1Rs)通过调控多种离子通道,从而调节脊椎动物视网膜的功能.本文旨在利用膜片钳全细胞记录技术,在大鼠视网膜薄片上研究CB1Rs对神经节细胞兴奋性的作用.结果显示,在电流钳制状态下,灌流CB1R激动剂WIN55212-2 (WIN,5μmol/L)对神经节细胞的自发动作电位发放频率和静息膜电位均没有显著影响.在灌流液中加入CNQX,D-APV,bicuculline

  6. 沉默信息调节因子1慢病毒表达载体的构建及其在视网膜神经节细胞中的表达%Construction of lentiviral vector containing sirt1 gene and its expression in retinal ganglion cell

    Institute of Scientific and Technical Information of China (English)

    姚青; 张继荣; 杨怡; 张茜; 李建宁; 孙玉宁

    2016-01-01

    Objective To construct a lentiviral vector carrying rat sirt1 gene and observe the expression of sirt1 in retinal ganglion cell (RGC) of rat.Methods Rat sirt1 cDNA was inserted into pLV5 vector.After identification by sequencing analysis and PCR,the recombinant sirt1expressinglentivirus vector was packaged by cotransfecting 293T cells with packaged plasmid.Then pLV5-sirt1 was used to infect the cultured Sprague-Dawley rat RGC cell in vitro.The expressions of sirt1 protein and mRNA in infected rat RGC were detected by quantitative real-time PCR and Western blot.Results The sirt1 expression vector pLV5 was successful constructed and sequence was proved to be correct.The expression of sirt1 protein and mRNA in RGC was significantly increased than that in cells infected with control lentiviruses (P < 0.05).Conclusion We have successful constructed a sirt1 expression lentivirus vector pLV5-sirt1 and it can increase the expression of sirt1 protein and mRNA in the rat retinal ganglion cells.%目的 构建沉默信息调节因子1(sirt1)过表达慢病毒载体,观察其在体外培养的视网膜神经节细胞(RGC)中的表达.方法 构建大鼠sirt1 cDNA的过表达慢病毒载体,采用PCR鉴定其是否构建成功.同时将其与GenBank上sirt1 cDNA标准序列进行对比分析.将鉴定后的慢病毒重组表达质粒pLV5-sirt1与包装质粒共转染293T细胞,制备携带sirt1的慢病毒pLV5-sirt1.体外培养Sprague-Dawley大鼠的RGC,应用pLV5-sirt1感染细胞设为sirt1过表达慢病毒组,同时设未感染组和空载体感染组.采用荧光显微镜观察细胞感染效率,实时PCR和蛋白免疫印迹法(Western blot)检测sirt1 mRNA和蛋白表达水平.结果 PCR鉴定结果显示,在1680碱基对处有扩增条带,表达的DNA条带与sirt1目的片段大小一致.与GenBank上sirt1cDNA标准序列进行对比分析,测序结果显示其含有与设计相同的靶序列.荧光显微镜观察发现,空载体感染组和sirt1过表达慢病毒

  7. Hyperpolarization-activated current (I(h in ganglion-cell photoreceptors.

    Directory of Open Access Journals (Sweden)

    Matthew J Van Hook

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGCs express the photopigment melanopsin and serve as the primary retinal drivers of non-image-forming visual functions such as circadian photoentrainment, the pupillary light reflex, and suppression of melatonin production in the pineal. Past electrophysiological studies of these cells have focused on their intrinsic photosensitivity and synaptic inputs. Much less is known about their voltage-gated channels and how these might shape their output to non-image-forming visual centers. Here, we show that rat ipRGCs retrolabeled from the suprachiasmatic nucleus (SCN express a hyperpolarization-activated inwardly-rectifying current (I(h. This current is blocked by the known I(h blockers ZD7288 and extracellular cesium. As in other systems, including other retinal ganglion cells, I(h in ipRGCs is characterized by slow kinetics and a slightly greater permeability for K(+ than for Na(+. Unlike in other systems, however, I(h in ipRGCs apparently does not actively contribute to resting membrane potential. We also explore non-specific effects of the common I(h blocker ZD7288 on rebound depolarization and evoked spiking and discuss possible functional roles of I(h in non-image-forming vision. This study is the first to characterize I(h in a well-defined population of retinal ganglion cells, namely SCN-projecting ipRGCs.

  8. Numerical simulation of neuronal spike patterns in a retinal network model

    Institute of Scientific and Technical Information of China (English)

    Lei Wang; Shenquan Liu; Shanxing Ou

    2011-01-01

    This study utilized a neuronal compartment model and NEURON software to study the effects of external light stimulation on retinal photoreceptors and spike patterns of neurons in a retinal network. Following light stimulation of different shapes and sizes, changes in the spike features of ganglion cells indicated that different shapes of light stimulation elicited different retinal responses. By manipulating the shape of light stimulation, we investigated the effects of the large number of electrical synapses existing between retinal neurons. Model simulation and analysis suggested that interplexiform cells play an important role in visual signal information processing in the retina, and the findings indicated that our constructed retinal network model was reliable and feasible. In addition, the simulation results demonstrated that ganglion cells exhibited a variety of spike patterns under different light stimulation sizes and different stimulation shapes, which reflect the functions of the retina in signal transmission and processing.

  9. 人脐血干细胞移植对大鼠外伤性视神经损伤后神经节细胞的保护作用%Protection of retinal ganglion cells from optic nerve injury by human umbilical cord blood stem cells transplantation

    Institute of Scientific and Technical Information of China (English)

    李云琴; 肖丽波; 康剑书; 张洁莹; 周圆; 邹悦

    2015-01-01

    目的 观察人脐血干细胞(hUCBSC)移植对视神经部分受损大鼠视网膜神经节细胞(RGC)的保护作用.方法 雄性Sprague-Dawley大鼠48只,随机分为A、B组,每组均为24只.大鼠暴露左眼视神经,在球后2 mm处用40 g力微型视神经夹垂直于视神经水平轴的视神经钳夹30 s建立部分视神经损伤模型.右眼为对照眼.建模后7d,A组大鼠左眼球周注射0.1 ml磷酸盐缓冲液;B组大鼠左眼球周注射0.1 ml hUCBSC悬液.处死大鼠前7d,双上丘注射5%荧光金(FG)逆行标记双眼RGC.FG逆行标记后7、14、21、28 d,两组分别随机选取6只大鼠行视网膜铺片,计数RGC并计算RGC标识率;作视网膜切片进行苏木精-伊红(HE)染色,观察视神经损伤后视网膜形态学变化.结果 随注射时间延长,A、B组大鼠RGC计数均呈下降趋势,B组大鼠损伤眼RGC计数下降幅度明显较A组平缓.A、B组大鼠损伤眼RGC计数均低于对照眼,差异有统计学意义(t=3.24、3.15,P<0.05).FG逆行标记后7、14、21、28 d,A、B组大鼠损伤眼RGC计数比较,差异均有统计学意义(t=4.78、4.70、3.98、3.27,P<0.05).FG逆行标记后7、14、21、28 d,A、B组组内大鼠RGC标识率比较,差异均有统计学意义(P<0.05);B组大鼠标识率较A组明显提高,差异均有统计学意义(t=4.39、4.21、4.36、5.07,P<0.05).光学显微镜观察发现,大鼠对照眼视网膜组织结构清晰,RGC层细胞排列规整.A、B组大鼠损伤眼视网膜各层变薄,RGC层核固缩、空泡样变性、细胞排列紊乱,RGC数量减少;损伤处视神经肿胀、出血,胶质细胞排列紊乱,空泡样变性,随损伤时间延长而加重.A组较B组病理改变更严重.结论 球周注射hUCBSC可减缓视神经损伤大鼠RGC凋亡,对RGC具有一定的保护作用.%Objective To observe the protective effect of human umbilical cord blood stem cells (hUCBSC) transplantation on retinal ganglion cells (RGC) after optic nerve injury.Method 48 adult

  10. 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.......e. Leber hereditary optic neuropathy and dominant optic atrophy. The mechanism leading to mRGCs sparing in these blinding disorders, characterized by extensive and selective loss of RGCs, is currently unknown and under investigation. Other studies reported on mRGCs in glaucoma, on genetic variation...

  11. 视网膜缺血再灌注损伤后视网膜神经节细胞pax6的表达变化与意义%Significance of pax6 expression in retinal ganglion cells after ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    李雪颖; 康前雁

    2012-01-01

    Objective To observe the expression of pax6 in retinal ganglion cells (RGC) and its significance after retinal ischemia-reperfusion (RIR) injury. Design Experimental study. Participants Rat model of RIR injury. Methods 30 adult female SD rats were randomly divided into 6 groups: group 1(n=5) normal control; group 2-6 (n=5 for each group) RIR injury groups (post injury 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks respectively). The intraocular pressure (IOP) of right eye was increased to induced RIR model. Pax6 expression was assessed by immunohistochemistry. Main Outcome Measures The expression of pax6. Results The positive rate of pax6 in RGC was (1.28±1.41) % in control group, (0.99±1.23)% in 1w group, (14.45±2.72)% in 2w group, (50.88±4.73)% in 4w group, (71.00±4.72)% in 6w group and (78.80±4.62) % in 8w group. The difference of expression of pax6 in RGC among these groups was significant (F=1.350, P<0.0001). Compared with control group, the expression of pax6 in RGC was significant higher in 2w, 4w, 6w and 8w group (all P<0.0001), but not significant different in lw group (P=0.835). Conclusion Pax6 expression was present in every layer of retina after RIR injury. RIR in rat induced activation of endogenous retinal stem cells.%目的 探索视网膜缺血再灌注损伤后视网膜神经节细胞pax6的表达变化及意义.设计实验研究.研究对象缺血再灌注损伤大鼠视网膜.方法 成年健康雄性Sprague-Dawley大鼠30只,随机选取5只作为空白对照组,其余25只为视网膜缺血再灌注损伤组,采用升高右眼眼压的方法制作视网膜缺血再灌注损伤模型.视网膜缺血再灌注后1、2、4、6、8周分5组,每组5只,不同时间点取右眼行免疫荧光染色,观察视网膜神经节细胞中pax6表达情况.主要指标pax6的表达.结果 视网膜缺血再灌注损伤后随着时间推移视网膜各层逐渐出现pax6表达阳性的细胞,对照组视网膜神经节细胞pax6表达阳性率为(1.28±1

  12. Cat Scan

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    <正> A man takes his motionless dog to the vet."Doc,I think my dog is dead.”The vet looks the dog over, goes into a backroom,and comes out with a cat.He places the caton the table next to the dog.The cat walks aroundand sniffs at the dog.The dog does not move.The

  13. Retinitis pigmentosa

    NARCIS (Netherlands)

    Hartong, Dyonne T.; Berson, Eliot L.; Dryja, Thaddeus P.

    2006-01-01

    Hereditary degenerations of the human retina are genetically heterogeneous, with well over 100 genes implicated so far. This Seminar focuses on the subset of diseases called retinitis pigmentosa, in which patients typically lose night vision in adolescence, side vision in young adulthood, and centra

  14. 优视胶囊对急性高眼压家兔眼压及神经节细胞的影响%Effects of Youshi capsule on the intraocular pressure(IOP) and retinal ganglion cells (RGC) of rabbits under artificial acute intraocular hypertension

    Institute of Scientific and Technical Information of China (English)

    张宗端; 段俊国

    2001-01-01

    目的:观察优视胶囊对急性高眼压兔眼压的影响及对视网膜视神经的保护作用。方法:采用自行设计的上巩膜静脉结扎法建立18只兔眼急性高眼压动物模型,于造模前1周至造模后3天共10天内给予具活血化瘀、开窍明目功效的优视胶囊灌胃,18只造模眼随机分为模型组、低剂量组和高剂量组,每组6眼,与18只正常眼进行对照。实验过程中测量眼压并行视网膜神经节细胞计数。结果:①造模后即可获得平均眼压高于6.83kPa并能持续3天以上的高眼压动物模型,优视胶囊高、低剂量组表现出轻微的降眼压作用。②持续性的高眼压可造成视网膜神经节细胞减少,但高、低剂量组经优视胶囊治疗后高眼压模型眼神经节细胞数高于模型组,提示优视胶囊具有保护或改善急性高眼压后兔眼视网膜神经节细胞的作用。结论:优视胶囊对急性高眼压兔眼视网膜视神经具有保护的作用。%Objective:To observe the effects of Youshi capsule on the intraocular pressure(IOP) and retinal ganglion cells(RGC) of rabbits under artificial acute intraocular hypertension.Methods:We used episcleral veins ligation on rabbit to establish an acute intraocular hypertension animal model devised by ourselves. Between one week before and 3 days after the models were induced, Youshi capsule was irrigated into the stomachs, having the function of promoting blood circulation and removing blood stasis,opening porus and improving vision. 18 model-established eyes were randomly divided into model group, high and low dosage group(6 eyes each group) and compared with other 18 normal eyes. Then examined IOP and counted RGC.Results:①Acute intraocular hypertension animal model was produced just after model was established and its average IOP above 6.83kPa could maintain 3 days. High and low dosage Youshi capsule showed slight effect on the reduction of IOP in intraocluar

  15. 霍乱毒素对金黄地鼠视网膜神经肽Y免疫 反应节细胞再生的影响%The Effects of Cholera Toxin on the Regeneration of Neuropeptide Y-Immunoreactive Retinal Ganglion Cells in Adult Golden Hamster

    Institute of Scientific and Technical Information of China (English)

    李雯; 李海标

    2001-01-01

    【Objective】 To examine the regeneration of NPY-immuno reactivity (IR) retinal ganglion cells (RGCs) and the effects of cholera toxin ( CTx) injected or/and peripheral nerve implanted on regeneration of NPY-IR RGCs. 【Methods】 16 adult golden hamsters were ramdomly divided into 4 groups. Optic nerve (ON) was transacted and a segment of autologous sciatic nerve (attached g raft, AG) was removed and sutured to the proximal stump of ON in regenerating co ntrol group (AG group). The animals in experimental groups were further treated with CTx injection or/and implantation of a short of segment sciatic nerve (SN) intravitrously. By using the retrograde labeling with fluorogold (FG) combined w ith fluorescent immunocytochemistry, the regenerated NPY-IR RGCs were observed and counted under fluorescent microscope. 【Results】 At 4 weeks after surgery, the mean number of regenerated NPY-IR RGCs per retina in AG group was 58±22 wh ich constitutes (3.36±0.65)% of the total regenerated RGCs. In AG+CTx, AG+SN and AG+CTx+SN experimental groups, the mean numbers of regenerated NPY-IR RGCs per retina were 143±47, 125±37 and 437±77 ordinally which constitute (5.15± 0.89)%, (5.34±0.37)% and (8.11±0.85)% of the total regenerated RGCs respec tively, which were increased significantly compared with those in AG group. 【Co nclusion】 The results show that the axotomized NPY-IR RGCs have th e capability of regenerating their axons into the attached PN graft, CTx and/or SN could enhance the regeneration of the NPY-IR RGCs.%: 【目的】 研究NPY免疫反应(IR)视网膜节细胞(RGCs)能否再 生及玻璃体内注射霍乱毒素(CTx)或/和玻璃体植入外周神经对其再生的影响。【方法】 16 只成年金黄地鼠随机分4组,每组4只动物。切断视神经(ON)并缝接坐骨神经(attached graf t, AG)为再生对照组即AG组;ON切断并缝接坐骨神经后再于玻璃体内注射CTx或/和植入小段 坐骨神经(SN)为实验组。荧光

  16. Focal electrical stimulation of major ganglion cell types in the primate retina for the design of visual prostheses.

    Science.gov (United States)

    Jepson, Lauren H; Hottowy, Pawel; Mathieson, Keith; Gunning, Deborah E; Dabrowski, Wladyslaw; Litke, Alan M; Chichilnisky, E J

    2013-04-24

    Electrical stimulation of retinal neurons with an advanced retinal prosthesis may eventually provide high-resolution artificial vision to the blind. However, the success of future prostheses depends on the ability to activate the major parallel visual pathways of the human visual system. Electrical stimulation of the five numerically dominant retinal ganglion cell types was investigated by simultaneous stimulation and recording in isolated peripheral primate (Macaca sp.) retina using multi-electrode arrays. ON and OFF midget, ON and OFF parasol, and small bistratified ganglion cells could all be activated directly to fire a single spike with submillisecond latency using brief pulses of current within established safety limits. Thresholds for electrical stimulation were similar in all five cell types. In many cases, a single cell could be specifically activated without activating neighboring cells of the same type or other types. These findings support the feasibility of direct electrical stimulation of the major visual pathways at or near their native spatial and temporal resolution.

  17. [Optogenetics and prosthetic treatment of retinal degeneration].

    Science.gov (United States)

    Kirpichnikov, M P; Ostrovskiy, M A

    2015-01-01

    This is a review of the current state of optogenetics-based research in the field of ophthalmology and physiology of vision. Optogenetics employs an interdisciplinary approach that amalgamates gene engineering, optics, and physiology. It involves exogenous expression of a light-activated protein in a very particular retinal cell enabling regulation (stimulation vs. inhibition) of its physiological activity. The experience with gene therapy came in very useful for optogenetics. However, unlike gene therapy, which is aimed at repairing damaged genes or replacing them with healthy ones, optogenetics is focused on protein genes delivery for further molecular control of the cell. In retina, the loss of photoreceptors is not necessarily followed by neuronal loss (at least ganglion cells remain intact), which determines the practicability of prosthetic treatment. Clinical trials can now be considered, owing to the first successful conversion of ganglion cells of mouse degenerative retinas into artificial photoreceptive cells with ON and OFF receptive fields, which is crucial for spatial vision. The following issues are reviewed here in detail: 1. Choice of cell targets within the degenerative retina. 2. Strategy of utilizing the existing light-sensitive agents and development of new optogenetic tools. 3. Gene delivery and expression in retinal cells. 4. Methods of evaluating the treatment success. 5. Selection criteria for optogenetic prosthetics. The conclusion discusses currently unsolved problems and prospects for optogenetic approaches to retinal prosthetics.

  18. Stem Cell Therapies in Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Aakriti Garg

    2017-02-01

    Full Text Available Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

  19. 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.

  20. 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.

  1. Cat and Dog Bites

    Science.gov (United States)

    ... Prevention and Wellness Staying Healthy Pets and Animals Cat and Dog Bites Cat and Dog Bites Pets and AnimalsPrevention and WellnessStaying Healthy Share Cat and Dog Bites Cat and dog bites are ...

  2. Cat Scratch Disease

    Science.gov (United States)

    Cat scratch disease (CSD) is an illness caused by the bacterium Bartonella henselae. Almost half of all cats carry ... infection does not make cats sick. However, the scratch or bite of an infected cat can cause ...

  3. Production of Retinal Cells from Confluent Human iPS Cells.

    Science.gov (United States)

    Reichman, Sacha; Goureau, Olivier

    2016-01-01

    Human induced pluripotent stem (hiPS) cells could be used as an unlimited source of retinal cells for the treatment of retinal degenerative diseases. Although much progress has been made in the differentiation of pluripotent stem cells towards different retinal lineages, the production of retinal cells from hiPS cells for therapeutic approaches require the development of easy and standardized protocols. In this chapter, we describe a simple and effective protocol for retinal differentiation of hiPS cells bypassing embryoid body formation and the use of exogenous molecules and substrates. In 2 weeks, confluent hiPS cells cultured in pro-neural medium can generate both retinal pigmented epithelial cells and self-forming neural retina-like structures containing retinal progenitor cells. These progenitors can be differentiated into all retinal cell types, including retinal ganglion cells and precursors of photoreceptors, which could find important applications in regenerative medicine. This differentiation system and the resulting hiPS-derived retinal cells will also offer opportunity to study the molecular and cellular mechanisms underlying human retinal development, and the establishment of in vitro models of human retinal degenerative diseases.

  4. Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis.

    Science.gov (United States)

    Syc, Stephanie B; Saidha, Shiv; Newsome, Scott D; Ratchford, John N; Levy, Michael; Ford, E'tona; Crainiceanu, Ciprian M; Durbin, Mary K; Oakley, Jonathan D; Meyer, Scott A; Frohman, Elliot M; Calabresi, Peter A

    2012-02-01

    Post-mortem ganglion cell dropout has been observed in multiple sclerosis; however, longitudinal in vivo assessment of retinal neuronal layers following acute optic neuritis remains largely unexplored. Peripapillary retinal nerve fibre layer thickness, measured by optical coherence tomography, has been proposed as an outcome measure in studies of neuroprotective agents in multiple sclerosis, yet potential swelling during the acute stages of optic neuritis may confound baseline measurements. The objective of this study was to ascertain whether patients with multiple sclerosis or neuromyelitis optica develop retinal neuronal layer pathology following acute optic neuritis, and to systematically characterize such changes in vivo over time. Spectral domain optical coherence tomography imaging, including automated retinal layer segmentation, was performed serially in 20 participants during the acute phase of optic neuritis, and again 3 and 6 months later. Imaging was performed cross-sectionally in 98 multiple sclerosis participants, 22 neuromyelitis optica participants and 72 healthy controls. Neuronal thinning was observed in the ganglion cell layer of eyes affected by acute optic neuritis 3 and 6 months after onset (P optica, with and without a history of optic neuritis, when compared with healthy controls (P optica and a history of optic neuritis exhibited the greatest reduction in ganglion cell layer thickness. Results from our in vivo longitudinal study demonstrate retinal neuronal layer thinning following acute optic neuritis, corroborating the hypothesis that axonal injury may cause neuronal pathology in multiple sclerosis. Further, these data provide evidence of subclinical disease activity, in both participants with multiple sclerosis and with neuromyelitis optica without a history of optic neuritis, a disease in which subclinical disease activity has not been widely appreciated. No pathology was seen in the inner or outer nuclear layers of eyes with optic

  5. My Cat

    Institute of Scientific and Technical Information of China (English)

    王悦; 李成梅

    2002-01-01

    The name of my cat is Naty. This year he is one year old. He isvery fat, but he is very nice. He has a big round white head. His mouth and nose are small. His eyes are interesting. In the day,they are small and black,but at night they are big and blue.

  6. Retinal vessel diameter changes induced by transient high perfusion pressure

    Institute of Scientific and Technical Information of China (English)

    Yin-Ying; Zhao; Ping-Jun; Chang; Fang; Yu; Yun-E; Zhao

    2014-01-01

    ·AIM: To investigate the effects of transient high perfusion pressure on the retinal vessel diameter and retinal ganglion cells.·METHODS: The animals were divided into four groups according to different infusion pressure and infusion time(60 mm Hg-3min, 60 mm Hg-5min, 100 mm Hg-3min, 100 mm Hg-5min). Each group consisted of six rabbits. The left eye was used as the experimental eye and the right as a control. Retinal vascular diameters were evaluated before, during infusion, immediately after infusion, 5min, 10 min and 30 min after infusion based on the fundus photographs. Blood pressure was monitored during infusion. The eyes were removed after 24 h.Damage to retinal ganglion cell(RGC) was analyzed by histology.·RESULTS: Retina became whiten and papilla optic was pale during perfusion. Measurements showed significant decrease in retinal artery and vein diameter during perfusion in all of the four groups at the proximal of the edge of the optic disc. The changes were significant in the 100 mm Hg-3min group and 100 mm Hg-5min group compared with 60 mm Hg-3min group(P 1=0.025, P 2=0.000).The diameters in all the groups recovered completely after 30 min of reperfusion. The number of RGC)showed no significant changes at the IOP in 100 mm Hg with5 min compared with contralateral untreated eye(P >0.05).·CONCLUSION: Transient fluctuations during infusion lead to temporal changes of retinal vessels, which could affect the retinal blood circulation. The RGCs were not affected by this transient fluctuation. Further studies are necessary to evaluate the effect of pressure during realtime phacoemusification on retinal blood circulation.

  7. Retinal abnormalities in multiple sclerosis patients with associated chronic cerebrospinal venous insufficiency

    OpenAIRE

    Aneta Adamczyk-Ludyga; Justyna Wróbeł; Marian Simka; Tomasz Ludyga; Paweł Latacz; Marek Kazibudzki

    2012-01-01

    Optical coherence tomography (OCT) is a non-invasive method for the assessment of optic nerve fibers and retinal ganglion cells. This study was aimed at the assessment of retinal abnormalities in multiple sclerosis patients in the context of chronic cerebrospinal venous insufficiency using OCT of the retina and the optic nerve. We examined 239 multiple sclerosis (MS) patients, including 220 patients with associated chronic cerebrospinal venous insufficiency and 19 MS patients without venous p...

  8. Retinal changes in an ATP-induced model of retinal degeneration

    Directory of Open Access Journals (Sweden)

    Felix Peter Aplin

    2016-04-01

    Full Text Available In rodents and felines, intravitreal administration of adenosine triphosphate (ATP has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG and optical coherence tomography (OCT. At 30 hours (n = 3 or 12 weeks (n = 3 post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labelled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 hours and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration.

  9. 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.

  10. A Catalogue of Anatomical Fugitive Sheets: Cat. 49-62

    OpenAIRE

    1999-01-01

    Images Cat. 50 Cat. 51 Cat. 53 Cat. 54 Cat. 55 (a) Cat. 55 (b) Cat. 56 Cat. 57: 1 Cat. 57: 2 Cat. 57: 3 Cat. 57: 4 Cat. 59: 1 Cat. 59: 2 Cat. 59: 3 Cat. 59: 4 Cat. 60 Cat. 61 Cat. 62: 1 (a) Cat. 62: 1 (b) Cat. 62: 2 (a) Cat. 62: 2 (b)

  11. A Catalogue of Anatomical Fugitive Sheets: Cat. 26-48

    OpenAIRE

    1999-01-01

    Images Cat. 26: 1 (a) Cat. 26: 1 (b) Cat. 26: 2 (a) Cat. 26: 2(b) Cat. 27: 1 (a) Cat. 27: 1 (b) Cat. 27: 2 (a) Cat. 27: 2 (b) Cat. 28 Cat. 29: 2 (a) Cat. 29: 2 (b) Cat. 30: 1 Cat. 30: 2 Cat. 30: 3 Cat. 33 Cat. 34: 1 Cat. 34: 2 Cat. 35: 1 Cat. 35: 2 Cat. 35: 3 Cat. 36 Cat. 37 Cat. 38: 1 Cat. 38: 2 Cat. 40 Cat. 42 Cat. 43 Cat. 44 Cat. 45: 1 Cat. 45: 2 Cat. 46 Cat. 47: 1 Cat. 47: 2 Cat. 47: 3 Cat. 48: 1 Cat. 48: 2 Cat. 48: 3

  12. black cat

    Institute of Scientific and Technical Information of China (English)

    杜铁梅

    2016-01-01

    The black cat is a masterpiece of short fiction of Poe. He successfully solved the problem of creating of the horror effect by using scene description, symbol, repetition and first-person narrative methods. And created a complete and unified mysterious terror, achieved the effect of shocking. This paper aims to discuss the mystery in-depth and to enrich the research system in Poe’s novels.

  13. A Disintegrin and Metalloproteinase10 (ADAM10 Regulates NOTCH Signaling during Early Retinal Development.

    Directory of Open Access Journals (Sweden)

    Joseph A Toonen

    Full Text Available ADAM10 and ADAM17 are two closely related members of the ADAM (a disintegrin and metalloprotease family of membrane-bound sheddases, which proteolytically cleave surface membrane proteins. Both ADAM10 and ADAM17 have been implicated in the proteolytic cleavage of NOTCH receptors and as such regulators of NOTCH signaling. During retinal development, NOTCH signaling facilitates retinal neurogenesis by maintaining progenitor cells in a proliferative state and by mediating retinal cell fates. However, the roles of ADAM10 and ADAM17 in the retina are not well defined. In this study, we set out to clarify the roles of ADAM10 and ADAM17 during early retinal development. The retinal phenotype of conditionally abated Adam17 retinae (Adam17 CKO did not differ from the controls whereas conditionally ablated Adam10 retinae (Adam10 CKO exhibited abnormal morphogenesis characterized by the formation of rosettes and a loss of retinal laminae phenotypically similar to morphological abnormalities identified in mice with retinal NOTCH signaling deficiency. Additionally, Adam10 CKO retinae exhibited abnormal neurogenesis characterized by fewer proliferating progenitor cells and greater differentiation of early photoreceptors and retinal ganglion cells. Moreover, constitutive activation of the NOTCH1-intracellular domain (N1-ICD rescued Adam10 CKO abnormal neurogenesis, as well as abnormal retinal morphology by maintaining retinal cells in the progenitor state. Collectively these findings provide in vivo genetic evidence that ADAM10, and not ADAM17, is indispensable for proper retinal development as a regulator of NOTCH signaling.

  14. A Disintegrin and Metalloproteinase10 (ADAM10) Regulates NOTCH Signaling during Early Retinal Development.

    Science.gov (United States)

    Toonen, Joseph A; Ronchetti, Adam; Sidjanin, D J

    2016-01-01

    ADAM10 and ADAM17 are two closely related members of the ADAM (a disintegrin and metalloprotease) family of membrane-bound sheddases, which proteolytically cleave surface membrane proteins. Both ADAM10 and ADAM17 have been implicated in the proteolytic cleavage of NOTCH receptors and as such regulators of NOTCH signaling. During retinal development, NOTCH signaling facilitates retinal neurogenesis by maintaining progenitor cells in a proliferative state and by mediating retinal cell fates. However, the roles of ADAM10 and ADAM17 in the retina are not well defined. In this study, we set out to clarify the roles of ADAM10 and ADAM17 during early retinal development. The retinal phenotype of conditionally abated Adam17 retinae (Adam17 CKO) did not differ from the controls whereas conditionally ablated Adam10 retinae (Adam10 CKO) exhibited abnormal morphogenesis characterized by the formation of rosettes and a loss of retinal laminae phenotypically similar to morphological abnormalities identified in mice with retinal NOTCH signaling deficiency. Additionally, Adam10 CKO retinae exhibited abnormal neurogenesis characterized by fewer proliferating progenitor cells and greater differentiation of early photoreceptors and retinal ganglion cells. Moreover, constitutive activation of the NOTCH1-intracellular domain (N1-ICD) rescued Adam10 CKO abnormal neurogenesis, as well as abnormal retinal morphology by maintaining retinal cells in the progenitor state. Collectively these findings provide in vivo genetic evidence that ADAM10, and not ADAM17, is indispensable for proper retinal development as a regulator of NOTCH signaling.

  15. Exploring the retinal connectome

    Science.gov (United States)

    Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Shaw, Margaret V.; Yang, Jia-Hui; DeMill, David; Lauritzen, James S.; Lin, Yanhua; Rapp, Kevin D.; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross

    2011-01-01

    Purpose A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. Methods We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Results Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive

  16. Transfection of brain-derived neurotrophic factor gene by recombinant adeno-associated virus vector in retinal ganglion cells in vitro%腺伴随病毒介导的脑源性神经营养因子对体外培养的鼠视网膜神经节细胞转染及生长特性的影响

    Institute of Scientific and Technical Information of China (English)

    李海燕; 赵家良; 张华

    2008-01-01

    目的 探讨重组腺伴随病毒载体介导的脑源性神经营养因子(rAAV-BDNF)对体外培养的鼠视网膜神经节细胞(RGCs)转染及其生长活性的影响.方法 实验研究.(1)应用rAAV-BDNF对体外培养2 d的RGCs进行转染;(2)应用逆转录聚合酶链反应(RT-PCR)技术,检测外源性BDNF基因在RGCs细胞mRNA水平的表达情况;(3)应用酶联免疫吸附测定(ELISA)法,对细胞培养液中BDNF含量进行检测;(4)对rAAV-BDNF转染细胞、未转染细胞及加入BDNF的培养细胞进行MTT比色分析;(5)应用Annexin V-FITC凋亡检测试剂盒和流式细胞仪,检测rAAV-BDNF转染细胞、未转染细胞及加入BDNF培养细胞的凋亡比率.结果 (1)RT-PCR检测结果:转染细胞表达外源性BDNF基因,而未转染细胞不表达BDNF基因.(2)ELISA法检测结果:rAAV-BDNF转染细胞的培养液中BDNF含量:转染7 d后为(616.1±40.0)ng/L,转染14 d后为(1075.1±48.7)ng/L.(3)MTT比色结果:转染3和6 d后,rAAV-BDNF转染细胞与未转染细胞间的吸光度(A)值差异无统计学意义(t=1.084,1.582;P=0.284,0.120);转染9 d后,转染细胞的A值高于未转染细胞(t=4.854,P=0.000).(4)流式细胞仪检测结果:rAAV-BDNF转染细胞和加入BDNF培养细胞的凋亡率明显低于未转染细胞的凋亡率,差异有统计学意义(P=0.015,0.017).结论 rAAV-BDNF可有效转染体外培养的鼠RGCs,转染细胞可在转录水平和翻译水平表达外源性BDNF基因,且生长活性改善,凋亡细胞减少.这为青光眼视神经保护的基因治疗提供了理论和技术支持.%Objective To determine whether rat retinal ganglion cells(RGCs)could be infected by rAAV-BDNF in vitro and to evaluate the influence of rAAV-BDNF transfection on the survival and apoptosis of rat RGCs.Methods It Was a experimental study.(1)RGCs were isolated from neonatal Sprague-Dawley rats(postnatal within 24 h).(2)Two days after the cultivation,the RGCs were transfected with rAAV- BDNF at a dosage of MOI=103 and then

  17. Retinal oscillations carry visual information to cortex

    Directory of Open Access Journals (Sweden)

    Kilian Koepsell

    2009-04-01

    Full Text Available Thalamic relay cells fire action potentials that transmit information from retina to cortex. The amount of information that spike trains encode is usually estimated from the precision of spike timing with respect to the stimulus. Sensory input, however, is only one factor that influences neural activity. For example, intrinsic dynamics, such as oscillations of networks of neurons, also modulate firing pattern. Here, we asked if retinal oscillations might help to convey information to neurons downstream. Specifically, we made whole-cell recordings from relay cells to reveal retinal inputs (EPSPs and thalamic outputs (spikes and then analyzed these events with information theory. Our results show that thalamic spike trains operate as two multiplexed channels. One channel, which occupies a low frequency band (<30 Hz, is encoded by average firing rate with respect to the stimulus and carries information about local changes in the visual field over time. The other operates in the gamma frequency band (40-80 Hz and is encoded by spike timing relative to retinal oscillations. At times, the second channel conveyed even more information than the first. Because retinal oscillations involve extensive networks of ganglion cells, it is likely that the second channel transmits information about global features of the visual scene.

  18. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Carbenoxolone blocks the light-evoked rise in intracellular calcium in isolated melanopsin ganglion cell photoreceptors.

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    Jayne R Bramley

    Full Text Available BACKGROUND: Retinal ganglion cells expressing the photopigment melanopsin are intrinsically photosensitive (ipRGCs. These ganglion cell photoreceptors send axons to several central targets involved in a variety of functions. Within the retina ipRGCs provide excitatory drive to dopaminergic amacrine cells via glutamatergic signals and ipRGCs are coupled to wide-field GABAergic amacrine cells via gap junctions. However, the extent to which ipRGCs are coupled to other retinal neurons in the ganglion cell layer via gap junctions is unclear. Carbenoxolone, a widely employed gap junction inhibitor, greatly reduces the number of retinal neurons exhibiting non-rod, non-cone mediated light-evoked Ca(2+ signals suggesting extensive intercellular coupling between ipRGCs and non-ipRGCs in the ganglion cell layer. However, carbenoxolone may directly inhibit light-evoked Ca(2+ signals in ipRGCs independent of gap junction blockade. METHODOLOGY/PRINCIPAL FINDINGS: To test the possibility that carbenoxolone directly inhibits light-evoked Ca(2+ responses in ipRGCs, the light-evoked rise in intracellular Ca(2+ ([Ca(2+](i was examined using fura-2 imaging in isolated rat ipRGCs maintained in short-term culture in the absence and presence of carbenoxolone. Carbenoxolone at 50 and 100 µM concentrations completely abolished the light-evoked rise in [Ca(2+](i in isolated ipRGCs. Recovery from carbenoxolone inhibition was variable. CONCLUSIONS/SIGNIFICANCE: We demonstrate that the light-evoked rise in [Ca(2+](i in isolated mammalian ganglion cell photoreceptors is inhibited by carbenoxolone. Since the light-evoked increase in [Ca(2+](i in isolated ipRGCs is almost entirely due to Ca(2+ entry via L-type voltage-gated calcium channels and carbenoxolone does not inhibit light-evoked action potential firing in ipRGCs in situ, carbenoxolone may block the light-evoked increase in [Ca(2+](i in ipRGCs by blocking L-type voltage-gated Ca(2+ channels. The ability of

  2. Ciliary neurotrophic factor-loaded polyethylene glycol-poly lactic-co-glycolic acid microbubbles combined with ultrasound for protection of retinal ganglion cells%载睫状神经营养因子聚乙二醇-乳酸/羟基乙酸共聚物微泡联合超声对视网膜神经节细胞的保护作用

    Institute of Scientific and Technical Information of China (English)

    王文婷; 刘苏; 王志刚; 周希瑗

    2013-01-01

    Objective To prepare and observe the properties of ciliary neurotrophic factor-loaded polyethylene glycol-poly lactic-co-glycolic acid ultrasound contrast agents (CNTF-PEG-PLGA),and to assess the protection effect of CNTFloaded PEG-PLGA microbubbles combined with ultrasound on retinal ganglion cells (RGCs) after optic nerve injury in rats.Methods CNTF-loaded PEG-PLGA ultrasound microbubbles were prepared using double emulsion technique,and the properties of the ultrasound microbubbles were observed.Totally 145 adult SD rats were randomly divided into 7 groups.After optic nerve injury,RGCs were retrograde labeled with the fluorescent tracer fluorogold (FG) to count RGCs number.The expressions of growth associated protein 43 (GAP-43) were detected by immunohistochemistry on the 3rd day,the 1st,the 2nd and the 4th week after optic nerve injury.The retinal pathological morphology change was observed at different times.Results CNTF-loaded PEG-PLGA ultrasound microbubbles were smooth and spherical with a mean size of (312.5± 57.35)nm,with the drug loading 0.298 μg/mg and encapsulation efficiency of 62.35%.There were 93.60%CNTF-PEG-PLGA release within 28 days.The results showed that after RGCs were retrograde labeled with FG,the RGCs count of group G was higher than that of other groups at every time,(all P<0.05),but less than group A (P<0.05).The expression of group G was higher than that of other groups (P<0.05) on the 1st,the 2nd and the 4th week after optic nerve injury.PEG-PLGA microbubbles did not induce any histology signs of ocular inflammation after their injection in the vitreous.Conclusion The ciliary neurotrophic factor-loaded PEG-PLGA microbubbles combined with ultrasound can protect retinal ganglion cells against after optic nerve injury in rats.%目的 制备载睫状神经营养因子(CNTF)的聚乙二醇(PEG)-乳酸/羟基乙酸共聚物(PLGA)超声微泡造影剂(CNTF-PEG-PLGA),观察其联合超声对视神经损伤大鼠视网膜神经节

  3. Neuroprotective Effects of Low-Dose Statins in the Retinal Ultrastructure of Hypercholesterolemic Rabbits.

    Science.gov (United States)

    Fernández-Navarro, Judith; Aldea, Pilar; de Hoz, Rosa; Salazar, Juan J; Ramírez, Ana I; Rojas, Blanca; Gallego, Beatriz I; Triviño, Alberto; Tejerina, Teresa; Ramírez, José M

    2016-01-01

    To evaluate the pleiotropic effects to statins, we analyze the qualitative and quantitative retinal changes in hypercholesterolemic rabbits after a low-dosage statin treatment. For this purpose, New Zealand rabbits were split into three groups: control (G0; n = 10), fed a standard diet; hypercholesterolemic (G1; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months; and statins (G2; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months, together with the administration of statin (pravastatin or fluvastatin sodium) at a dose of 2 mg / kg / day each diet. The retinas were analyzed by transmission electron microscopy and immunohistochemistry (glial fibrillary acidic protein). The retinal thickness of nuclear and plexiform layers were quantified in semi-thin sections. The results revealed that the low-statin-treated rabbits in comparison with the hypercholesterolemic group showed: i) a more preserved structure in all retinal layers; ii) a significant reduction in retinal thickness; iii) a decrease in cell death in the nuclear-and ganglion-cell layers; iv) a reduction of hydropic degeneration in the plexiform and nerve-fiber layers; v) a preservation of astrocytes and of the retinal area occupied by them; and vi) a better-preserved retinal vascular structure. Our findings indicate that low doses of statins can prevent retinal degeneration, acting on retinal macroglia, neurons and retinal vessels, despite that hypercholesterolemia remained unchanged. Thus, the pleiotropic effects of the statins may help safeguard the retinal ultrastructure.

  4. Virtual electrode design for increasing spatial resolution in retinal prosthesis.

    Science.gov (United States)

    Loizos, Kyle; Cela, Carlos; Marc, Robert; Lazzi, Gianluca

    2016-06-01

    Retinal prostheses systems are currently used to restore partial vision to patients blinded by degenerative diseases by electrically stimulating surviving retinal cells. To obtain likely maximum resolution, electrode size is minimised, allowing for a large quantity on an array and localised stimulation regions. Besides the small size leading to fabrication difficulties and higher electrochemical charge density, there are challenges associated with the number of drivers needed for a large electrode count as well as the strategies to deliver sufficient power to these drivers wirelessly. In hopes to increase electrode resolution while avoiding these issues, the authors propose a new 'virtual electrode' design to increase locations of likely stimulation. Passive metallisation strategically placed between disk electrodes, combined with alternating surrounding stimuli, channel current into a location between electrodes, producing a virtual stimulation site. A computational study was conducted to optimise the passive metal element geometry, quantify the expected current density output, and simulate retinal ganglion cell activity due to virtual electrode stimulation. Results show that this procedure leads to array geometry that focuses injected current and achieves retinal ganglion cell stimulation in a region beneath the 'virtual electrode,' creating an alternate stimulation site without additional drivers.

  5. 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.

  6. Cat Scratch Disease: Expanded Spectrum

    Science.gov (United States)

    Aziz, Hassan A.; Plesec, Thomas P.; Sabella, Camille; Udayasankar, Unni K.; Singh, Arun D.

    2016-01-01

    Background To expand the spectrum of ophthalmic manifestations in cat scratch disease. Methods Case report. Results A 7-year-old male was referred for evaluation of his left optic disc after failing vision screening test at school. His visual acuity was 20/20 OD and light perception OS. Fundus examination showed a left optic disc lesion associated with an exudative retinal detachment and vitreous seeding. Ultrasonography revealed a 7 × 7.5 × 3.8 mm lesion with a possible 6.3 mm of retrolaminar extension into the substance of the optic nerve. Brain MRI did not show evidence of optic nerve involvement but revealed a 6-mm nodule of the pineal gland suggestive of a pineoblastoma. Enucleation was performed and histopathology revealed a suppurative granulomatous inflammation suggestive of Bartonella infection. Upon further questioning, the patient had recent exposure to kittens with areas of cat scratches along both of his arms. He was subsequently referred to and treated with a 2-week course of trimethoprim-sulfamethoxazole and rifampin by the pediatric infectious disease specialist. Repeat brain MRI showed interval total resolution of enlarged pineal gland. Conclusion: Optic nerve granulomas are a rare presentation of cat scratch disease and could potentially masquerade as retinoblastoma. PMID:27843905

  7. Protective effect of neuroglobin on retinal ganglion cell in glaucoma mice model%神经球蛋白对慢性高眼压小鼠视网膜神经节细胞损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    魏欣; 刘旭阳; 邓应平; 陈晓明

    2012-01-01

    .05).1周时,Ngb-Tg小鼠微球单次注射组视网膜中DHE含量明显低于WT小鼠微球单次注射组(t=3.212,P=0.008),而ATP的含量则明显高于WT小鼠微球单次注射组(t=2.864,P<0.01). 结论 Ngb可能是青光眼损伤的内源性神经保护因子,对高眼压所致RGCs损伤有保护作用,其机制可能是通过降低氧化应激和改善线粒体功能实现的.%Background Neuroglobin (Ngb) is a newly discovered member of globin superfamily.It is thought to regulate cell survival under hypoxia or oxidative stress condition.Ngb is expressed at a high level in retinal neuron,suggesting that retina may be one of important functional sites of Ngb.Objective The aim of this study was to investigate the protective role of endogenous Ngb on retina ganglion cells (RGCs) following chronic high intraocular pressure(IOP)in mice and the underlying mechanisms.Methods This study included the in vitro and in vivo experiment.RGCs derived from adult C57BL/6J wild type(WT) mice and Ngb-transgenic(Ngb-Tg) mice which cultivated by our laboratory were incubated with 5.0,7.5,10.0 mmol/L glutamic acid for 3 days.RGCs survival rate was calculated for the ration of dead and survival cells using a double labeling kit to evaluate the influence of Ngb on RGCs survival rate in the addition of glutamic acid.Chronic ocular hypertension models were established by injection of fluorescent microballon(MB) (10 μm)into the anterior chamber of WT mice and Ngb-Tg mice,The mice were divided into WT control group(n=18),Ngb-Tg control group(n=30),WT+MB single injection group(n=38),Ngb-Tg+MB single injection group (n =38),WT+MB twice injection group (n =6) and Ngb-Tg + twice injection group (n=6).In addition,WT+PBS injection group (n =6) and Ngb-Tg+ PBS injection group (n =6) were designed as negative controls to identify if it can affect IOP or not.The mice were sacrificed on 0 day(control group),3 days and 1,4,8 weeks followed the MB anterior chamber injection.Real-time PCR

  8. Retinal projection to the pretectal nucleus lentiformis mesencephali in pigeons (Columba livia).

    Science.gov (United States)

    Wylie, Douglas R; Kolominsky, Jeffrey; Graham, David J; Lisney, Thomas J; Gutierrez-Ibanez, Cristian

    2014-12-01

    In birds, the nucleus of the basal optic root (nBOR) and the nucleus lentiformis mesencephali (LM) are retinal-recipient nuclei involved in the analysis of optic flow and the generation of the optokinetic response. The nBOR receives retinal input from displaced ganglion cells (DGCs), which are found at the margin of the inner nuclear and inner plexiform layers, rather than the ganglion cell layer. The LM receives afferents from retinal ganglion cells, but whether DGCs also project to LM remains unclear. To resolve this issue, we made small injections of retrograde tracer into LM and examined horizontal sections through the retina. For comparison, we also had cases with injections in nBOR, the optic tectum, and the anterior dorsolateral thalamus (the equivalent to the mammalian lateral geniculate nucleus). From all LM injections both retinal ganglion cells and DGCs were labeled. The percentage of DGCs, as a proportion of all labeled cells, varied from 2-28%, and these were not different in morphology or size compared to those labeled from nBOR, in which the proportion of DGCs was much higher (84-93%). DGCs were also labeled after injections into the anterior dorsolateral thalamus. The proportion was small (2-3%), and these DGCs were smaller in size than those projecting to the nBOR and LM. No DGCs were labeled from an injection in the optic tectum. Based on an analysis of size, we suggest that different populations of retinal ganglion cells are involved in the projections to LM, nBOR, the optic tectum, and the anterior dorsolateral thalamus.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Characterization of Three-Dimensional Retinal Tissue Derived from Human Embryonic Stem Cells in Adherent Monolayer Cultures

    Science.gov (United States)

    Singh, Ratnesh K.; Mallela, Ramya K.; Cornuet, Pamela K.; Reifler, Aaron N.; Chervenak, Andrew P.; West, Michael D.; Wong, Kwoon Y.; Nasonkin, Igor O.

    2015-01-01

    Stem cell-based therapy of retinal degenerative conditions is a promising modality to treat blindness, but requires new strategies to improve the number of functionally integrating cells. Grafting semidifferentiated retinal tissue rather than progenitors allows preservation of tissue structure and connectivity in retinal grafts, mandatory for vision restoration. Using human embryonic stem cells (hESCs), we derived retinal tissue growing in adherent conditions consisting of conjoined neural retina and retinal pigment epithelial (RPE) cells and evaluated cell fate determination and maturation in this tissue. We found that deriving such tissue in adherent conditions robustly induces all eye field genes (RX, PAX6, LHX2, SIX3, SIX6) and produces four layers of pure populations of retinal cells: RPE (expressing NHERF1, EZRIN, RPE65, DCT, TYR, TYRP, MITF, PMEL), early photoreceptors (PRs) (coexpressing CRX and RCVRN), inner nuclear layer neurons (expressing CALB2), and retinal ganglion cells [RGCs, expressing BRN3B and Neurofilament (NF) 200]. Furthermore, we found that retinal progenitors divide at the apical side of the hESC-derived retinal tissue (next to the RPE layer) and then migrate toward the basal side, similar to that found during embryonic retinogenesis. We detected synaptogenesis in hESC-derived retinal tissue, and found neurons containing many synaptophysin-positive boutons within the RGC and PR layers. We also observed long NF200-positive axons projected by RGCs toward the apical side. Whole-cell recordings demonstrated that putative amacrine and/or ganglion cells exhibited electrophysiological responses reminiscent of those in normal retinal neurons. These responses included voltage-gated Na+ and K+ currents, depolarization-induced spiking, and responses to neurotransmitter receptor agonists. Differentiation in adherent conditions allows generation of long and flexible pieces of 3D retinal tissue suitable for isolating transplantable slices of tissue for

  11. Effect of Purified Murine NGF on Isolated Photoreceptors of a Rodent Developing Retinitis Pigmentosa

    Science.gov (United States)

    Rocco, Maria Luisa; Balzamino, Bijorn Omar; Petrocchi Passeri, Pamela; Micera, Alessandra; Aloe, Luigi

    2015-01-01

    A number of different studies have shown that neurotrophins, including nerve growth factor (NGF) support the survival of retinal ganglion neurons during a variety if insults. Recently, we have reported that that eye NGF administration can protect also photoreceptor degeneration in a mice and rat with inherited retinitis pigmentosa. However, the evidence that NGF acts directly on photoreceptors and that other retinal cells mediate the NGF effect could not be excluded. In the present study we have isolated retinal cells from rats with inherited retinitis pigmentosa (RP) during the post-natal stage of photoreceptor degenerative. In presence of NGF, these cells are characterized by enhanced expression of NGF-receptors and rhodopsin, the specific marker of photoreceptor and better cell survival, as well as neuritis outgrowth. Together these observations support the hypothesis that NGF that NGF acts directly on photoreceptors survival and prevents photoreceptor degeneration as previously suggested by in vivo studies. PMID:25897972

  12. Dark rearing maintains tyrosine hydroxylase expression in retinal amacrine cells following optic nerve transection

    Institute of Scientific and Technical Information of China (English)

    Wei Wan; Zhenghai Liu; Xiaosheng Wang; Xuegang Luo

    2012-01-01

    The present study examined changes in retinal tyrosine hydroxylase (TH) expression in rats having undergone optic nerve transection and housed under a normal day/night cycle or in the dark. The aim was to investigate the effects of amacrine cells on axonal regeneration in retinal ganglion cells and on the synapses that transmit visual signals. The results revealed that retinal TH expression gradually decreased following optic nerve transection in rats housed under a normal day/night cycle, reaching a minimum at 5 days. In contrast, retinal TH expression decreased to a minimum at 1 day following optic nerve transection in dark reared rats, gradually increasing afterward and reaching a normal level at 5-7 days. The number of TH-positive synaptic particles correlated with the TH levels, indicating that dark rearing can help maintain TH expression during the synaptic degeneration stage (5-7 days after optic nerve injury) in retinal amacrine cells.

  13. 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.

  14. Neural differentiation and synaptogenesis in retinal development.

    Science.gov (United States)

    Fan, Wen-Juan; Li, Xue; Yao, Huan-Ling; Deng, Jie-Xin; Liu, Hong-Liang; Cui, Zhan-Jun; Wang, Qiang; Wu, Ping; Deng, Jin-Bo

    2016-02-01

    To investigate the pattern of neural differentiation and synaptogenesis in the mouse retina, immunolabeling, BrdU assay and transmission electron microscopy were used. We show that the neuroblastic cell layer is the germinal zone for neural differentiation and retinal lamination. Ganglion cells differentiated initially at embryonic day 13 (E13), and at E18 horizontal cells appeared in the neuroblastic cell layer. Neural stem cells in the outer neuroblastic cell layer differentiated into photoreceptor cells as early as postnatal day 0 (P0), and neural stem cells in the inner neuroblastic cell layer differentiated into bipolar cells at P7. Synapses in the retina were mainly located in the outer and inner plexiform layers. At P7, synaptophysin immunostaining appeared in presynaptic terminals in the outer and inner plexiform layers with button-like structures. After P14, presynaptic buttons were concentrated in outer and inner plexiform layers with strong staining. These data indicate that neural differentiation and synaptogenesis in the retina play important roles in the formation of retinal neural circuitry. Our study showed that the period before P14, especially between P0 and P14, represents a critical period during retinal development. Mouse eye opening occurs during that period, suggesting that cell differentiation and synaptic formation lead to the attainment of visual function.

  15. 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.

  16. Non-Coding RNAs in Retinal Development

    Directory of Open Access Journals (Sweden)

    Robert Hindges

    2012-01-01

    Full Text Available Retinal development is dependent on an accurately functioning network of transcriptional and translational regulators. Among the diverse classes of molecules involved, non-coding RNAs (ncRNAs play a significant role. Members of this family are present in the cell as transcripts, but are not translated into proteins. MicroRNAs (miRNAs are small ncRNAs that act as post-transcriptional regulators. During the last decade, they have been implicated in a variety of biological processes, including the development of the nervous system. On the other hand, long-ncRNAs (lncRNAs represent a different class of ncRNAs that act mainly through processes involving chromatin remodeling and epigenetic mechanisms. The visual system is a prominent model to investigate the molecular mechanisms underlying neurogenesis or circuit formation and function, including the differentiation of retinal progenitor cells to generate the seven principal cell classes in the retina, pathfinding decisions of retinal ganglion cell axons in order to establish the correct connectivity from the eye to the brain proper, and activity-dependent mechanisms for the functionality of visual circuits. Recent findings have associated ncRNAs in several of these processes and uncovered a new level of complexity for the existing regulatory mechanisms. This review summarizes and highlights the impact of ncRNAs during the development of the vertebrate visual system, with a specific focus on the role of miRNAs and a synopsis regarding recent findings on lncRNAs in the retina.

  17. Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons

    Science.gov (United States)

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

    2016-08-01

    Objective. The field of retinal prosthetics has made major progress over the last decade, restoring visual percepts to people suffering from retinitis pigmentosa. The stimulation pulses used by present implants are suprathreshold, meaning individual pulses are designed to activate the retina. In this paper we explore subthreshold pulse sequences as an alternate stimulation paradigm. Subthreshold pulses have the potential to address important open problems such as fading of visual percepts when patients are stimulated at moderate pulse repetition rates and the difficulty in preferentially stimulating different retinal pathways. Approach. As a first step in addressing these issues we used Gaussian white noise electrical stimulation combined with spike-triggered averaging to interrogate whether a subthreshold sequence of pulses can be used to activate the mouse retina. Main results. We demonstrate that the retinal network can integrate multiple subthreshold electrical stimuli under an experimental paradigm immediately relevant to retinal prostheses. Furthermore, these characteristic stimulus sequences varied in their shape and integration window length across the population of retinal ganglion cells. Significance. Because the subthreshold sequences activate the retina at stimulation rates that would typically induce strong fading (25 Hz), such retinal ‘tickling’ has the potential to minimize the fading problem. Furthermore, the diversity found across the cell population in characteristic pulse sequences suggests that these sequences could be used to selectively address the different retinal pathways (e.g. ON versus OFF). Both of these outcomes may significantly improve visual perception in retinal implant patients.

  18. Effect of retinal ischemia on the non-image forming visual system.

    Science.gov (United States)

    González Fleitas, María Florencia; Bordone, Melina; Rosenstein, Ruth E; Dorfman, Damián

    2015-03-01

    Retinal ischemic injury is an important cause of visual impairment. The loss of retinal ganglion cells (RGCs) is a key sign of retinal ischemic damage. A subset of RGCs expressing the photopigment melanopsin (mRGCs) regulates non-image-forming visual functions such as the pupillary light reflex (PLR), and circadian rhythms. We studied the effect of retinal ischemia on mRGCs and the non-image-forming visual system function. For this purpose, transient ischemia was induced by raising intraocular pressure to 120 mm Hg for 40 min followed by retinal reperfusion by restoring normal pressure. At 4 weeks post-treatment, animals were subjected to electroretinography and histological analysis. Ischemia induced a significant retinal dysfunction and histological alterations. At this time point, a significant decrease in the number of Brn3a(+) RGCs and in the anterograde transport from the retina to the superior colliculus and lateral geniculate nucleus was observed, whereas no differences in the number of mRGCs, melanopsin levels, and retinal projections to the suprachiasmatic nuclei and the olivary pretectal nucleus were detected. At low light intensity, a decrease in pupil constriction was observed in intact eyes contralateral to ischemic eyes, whereas at high light intensity, retinal ischemia did not affect the consensual PLR. Animals with ischemia in both eyes showed a conserved locomotor activity rhythm and a photoentrainment rate which did not differ from control animals. These results suggest that the non-image forming visual system was protected against retinal ischemic damage.

  19. Stimulus-specific oscillations in a retinal model.

    Science.gov (United States)

    Kenyon, Garrett T; Travis, Bryan J; Theiler, James; George, John S; Stephens, Gregory J; Marshak, David W

    2004-09-01

    High-frequency oscillatory potentials (HFOPs) in the vertebrate retina are stimulus specific. The phases of HFOPs recorded at any given retinal location drift randomly over time, but regions activated by the same stimulus tend to remain phase locked with approximately zero lag, whereas regions activated by spatially separate stimuli are typically uncorrelated. Based on retinal anatomy, we previously postulated that HFOPs are mediated by feedback from a class of axon-bearing amacrine cells that receive excitation from neighboring ganglion cells-via gap junctions-and make inhibitory synapses back onto the surrounding ganglion cells. Using a computer model, we show here that such circuitry can account for the stimulus specificity of HFOPs in response to both high- and low-contrast features. Phase locking between pairs of model ganglion cells did not depend critically on their separation distance, but on whether the applied stimulus created a continuous path between them. The degree of phase locking between spatially separate stimuli was reduced by lateral inhibition, which created a buffer zone around strongly activated regions. Stimulating the inhibited region between spatially separate stimuli increased their degree of phase locking proportionately. Our results suggest several experimental strategies for testing the hypothesis that stimulus-specific HFOPs arise from axon-mediated feedback in the inner retina.

  20. Calcium influx and calpain activation mediate preclinical retinal neurodegeneration in autoimmune optic neuritis.

    Science.gov (United States)

    Hoffmann, Dorit B; Williams, Sarah K; Bojcevski, Jovana; Müller, Andreas; Stadelmann, Christine; Naidoo, Vinogran; Bahr, Ben A; Diem, Ricarda; Fairless, Richard

    2013-08-01

    Optic neuritis is a common manifestation of multiple sclerosis, an inflammatory demyelinating disease of the CNS. Recently, the neurodegenerative component of multiple sclerosis has come under focus particularly because permanent disability in patients correlates well with neurodegeneration; and observations in both humans and multiple sclerosis animal models highlight neurodegeneration of retinal ganglion cells as an early event. After myelin oligodendrocyte glycoprotein immunization of Brown Norway rats, significant retinal ganglion cell loss precedes the onset of pathologically defined autoimmune optic neuritis. To study the role calcium and calpain activation may play in mediating early degeneration, manganese-enhanced magnetic resonance imaging was used to monitor preclinical calcium elevations in the retina and optic nerve of myelin oligodendrocyte glycoprotein-immunized Brown Norway rats. Calcium elevation correlated with an increase in calpain activation during the induction phase of optic neuritis, as revealed by increased calpain-specific cleavage of spectrin. The relevance of early calpain activation to neurodegeneration during disease induction was addressed by performing treatment studies with the calpain inhibitor calpeptin. Treatment not only reduced calpain activity but also protected retinal ganglion cells from preclinical degeneration. These data indicate that elevation of retinal calcium levels and calpain activation are early events in autoimmune optic neuritis, providing a potential therapeutic target for neuroprotection.

  1. Interconnection between brain and retinal neurodegenerations.

    Science.gov (United States)

    Jindal, Vishal

    2015-01-01

    The eye is a special sensory organ, which is basically an extension of the brain. Both are derived from neural tube and consist of neurons. Therefore, diseases of both the brain and eye should have some similarity. Neurodegenerative disorders like Alzheimer's disease (AD) is the major cause of dementia in the world. Amyloid deposition in the cerebral cortex and hippocampal region is the basic pathology in AD. But along with it, there are various changes that take place in the eye, i.e., abnormal pupillary reaction, decreased vision, decreased contrast sensitivity, visual field changes, loss of retinal ganglionic cells and retinal fiber layer, peripapillary atrophy, increased cup-disk ratio, retinal thinning, tortuosity of blood vessels, and deposition of Aβ-like substance in the retina. And these changes are present in the early part of the disease when only mild cognitive impairment is there. As the brain is covered by a hard bony skull which makes it difficult to directly visualize the changes occurring in the brain at molecular levels, finer details of disease progression are not available with us. But the eye is the window of the brain; with advanced modern techniques, we can directly visualize the changes in the retina at a very fine level. Therefore, by depicting neurodegenerative changes in the eye, we can diagnose and manage AD at very early stages. Along with it, retinal neurodegenerations like glaucoma and age-related macular degeneration (ARMD) are the major cause of loss of vision, and still, there are no effective treatment modalities for these blinding conditions. So if we can understand its pathogenesis and progression by correlating with brain neurodegenerations, we can come up with a better therapy for glaucoma and ARMD.

  2. 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

  3. Retinal remodeling in human retinitis pigmentosa.

    Science.gov (United States)

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E

    2016-09-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

  4. Beta-adrenoceptor-mediated vasodilation of retinal blood vessels is reduced in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Nakazawa, Taisuke; Sato, Ayumi; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-01-01

    We investigated the effects of epinephrine and dopamine on retinal blood vessels in streptozotocin (STZ, 80 mg/kg, i.p.)-treated rats and age-matched control rats to determine whether diabetes mellitus alters the retinal vascular responses to circulating catecholamines. Experiments were performed 6-8 weeks after treatment with STZ or the vehicle. The fundus images were captured with the digital fundus camera system for small animals we developed and diameters of retinal blood vessels contained in the digital images were measured. Epinephrine increased the diameters of retinal blood vessels, but the vasodilator responses were reduced in diabetic rats. Dopamine produced a biphasic retinal vascular response with an initial vasoconstriction followed by a vasodilation. The vasoconstrictor effects of dopamine on retinal arterioles were enhanced in diabetic rats, whereas the difference between the two groups was abolished by treatment with propranolol. The vasodilator effect of isoproterenol, but not of the activator of adenylyl cyclase colforsin, on retinal blood vessels was reduced in diabetic rats. No difference in vasoconstriction of retinal blood vessels to phenylephrine between non-diabetic and diabetic rats was observed. The vasodilator responses of retinal blood vessels to 1,1-dimethyl-4-phenylpiperazinium, a ganglionic nicotinic receptor agonist, were also attenuated in diabetic rats. These results suggest that diabetes mellitus alters the retinal vascular responses to circulating catecholamines and the impairment of vasodilator responses mediated by beta-adrenoceptors contributes to the alteration.

  5. Postnatal visual deprivation in rats regulates several retinal genes and proteins, including differentiation-associated fibroblast growth factor-2.

    Science.gov (United States)

    Prokosch-Willing, Verena; Meyer zu Hoerste, Melissa; Mertsch, Sonja; Stupp, Tobias; Thanos, Solon

    2015-01-01

    Little is known about the retinal cellular basis of amblyopia, which is a developmental disease characterized by impaired visual acuity. This study examined the retinal transcripts associated with experimentally induced unilateral amblyopia in rats. Surgical tarsorrhaphy of the eyelids on one side was performed in pups prior to eye opening at postnatal day 14, thereby preventing any visual experience. This condition was maintained for over 2 months, after which electroretinograms (ERGs) were recorded, the retinal ganglion cell (RGC) arrangement and number were determined using neuroanatomical tracing, the retinal transcripts were studied using microarray analysis, regulated mRNAs were confirmed with quantitative reverse-transcriptase PCR, and proteins were stained using Western blotting and immunohistochemistry. An attenuated ERG was found in eyes that were deprived of visual experience. Retrograde neuroanatomical staining disclosed a larger number of RGCs within the retina on the visually deprived side compared to the non-deprived, control side, and a multilayered distribution of RGCs. At the retinomic level, several transcripts associated with retinal differentiation, such as fibroblast growth factor 2 (FGF-2), were either up- or downregulated. Most of the transcripts could be verified at the mRNA level. To unravel the role of a differentiation-associated protein, we tested FGF-2 in dissociated postnatal retinal cell cultures and found that FGF-2 is a potent factor triggering ganglion cell differentiation. The data suggest that visual experience shapes the postnatal retinal differentiation, whereas visual deprivation induces changes at the functional, cellular and molecular levels within the retina.

  6. Physiological variation of segmented OCT retinal layer thicknesses is short-lasting.

    Science.gov (United States)

    Balk, Lisanne; Mayer, Markus; Uitdehaag, Bernard M J; Petzold, Axel

    2013-12-01

    The application of spectral domain optical coherence tomography as a surrogate for neurodegeneration in a range of neurological disorders demands better understanding of the physiological variation of retinal layer thicknesses, which may mask any value of this emerging outcome measure. A prospective study compared retinal layer thicknesses between control subjects (n = 15) and runners (n = 27) participating in a 10-km charity run. Three scans were performed using an eye-tracking function (EBF) and automated scan registration for optimal precision at (1) baseline, (2) directly after the run, and (3) following a rehydration period. Retinal layer segmentation was performed with suppression of axial retinal vessel signal artifacts. Following the run, there was an increase in the relative retinal nerve fibre layer (p = 0.018), the combined inner plexiform/ganglion cell layer (p = 0.038), and the outer nuclear layer (p = 0.018) in runners compared to controls. The initial increase of thickness in the outer nuclear layer of runners (p < 0.0001) was likely related to (noncompliant) rehydration during exercise. Following a period of rest and rehydration, the difference in thickness change for all retinal layers, except the retinal nerve fibre layer (RNFL) (p < 0.05), disappeared between the two groups. There is a quantifiable change in the axial thickness of retinal layersthat which can be explained by an increase in the cellular volume. This effect may potentially be caused by H2O volume shifts.

  7. [Retinal and trabecular degeneration in glaucoma: new insights into pathogenesis and treatment].

    Science.gov (United States)

    Denoyer, A; Roubeix, C; Sapienza, A; Réaux-Le Goazigo, A; Mélik-Parsadaniantz, S; Baudouin, C

    2015-04-01

    Academic and industrial research has brought new insights into the pathogenesis of glaucoma, aiming at identifying and targeting specific mechanisms to improve our current therapeutic strategy. Retinal neurodegeneration is still the main focus, whether in terms of extrinsic factors such as neurotrophin deprivation, glutamate toxicity, vascular deficiency and neuro-inflammation from glial cells, or in terms of retinal ganglion cell intrinsic sensibility to proapoptotic signals. However, glaucoma is not solely a retinal disease but also involves retinal and trabecular meshwork degeneration, extending into and/or even originating from the brain. The present review summarizes our current knowledge of key mechanisms involved in glaucoma degeneration, focusing on the direction of current research towards the future of glaucoma therapy.

  8. Early and late inner retinal changes after inner limiting membrane peeling.

    Science.gov (United States)

    Pichi, Francesco; Lembo, Andrea; Morara, Mariachiara; Veronese, Chiara; Alkabes, Micol; Nucci, Paolo; Ciardella, Antonio P

    2014-04-01

    Pars plana vitrectomy and inner limiting membrane (ILM) peeling are standard procedures for macular hole and epiretinal membrane surgery. However, ILM peeling is known to cause mechanical traumatic changes to the retinal nerve fiber layer. Recently there have been numerous reports of anatomical changes in the macula after ILM removal. A comprehensive review of the literature. The earliest change in the macula after ILM peeling is post-operative swelling of the arcuate retinal nerve fiber layer (SANFL), which disappears within the 3 month; the swelling is not detected on biomicroscopic fundus examination but appears as hypoautofluorescent arcuate striae in the macular region on infrared and autofluorescence imaging, with corresponding hyperreflectant swelling demonstrated on spectral-domain optical coherence tomography (OCT). SANFL is followed by dissociated optic nerve fiber layer defect, faintly visible on fundus examination and corresponding on OCT to "dimples" in the inner retinal layers. The en face tomographic aspect of this defect appears as concentric macular dark spots. Post-operative foveal displacement toward the optic disc might be responsible for the stretching and thinning of the retinal parenchyma in the temporal subfield and the thickening of the nasal macula. This shortening of the papillofoveal distance after surgery is probably secondary to axonal transport and contractility alterations in the nerve fiber layer, which might also account for apoptotic and atrophic degeneration of the peripapillary retinal nerve fiber layer. Ganglion cells do not seem to be affected by ILM peeling, even if the ganglion cell complex loses some volume because of trauma to the Müller cells contained in the ganglion cell layer. Despite its clear indication in macular hole and epiretinal membrane surgery, ILM peeling is a traumatic procedure that has acute effects on the underlying inner retinal layers. Further investigation of these subclinical changes may assist in

  9. 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.

  10. Does retinal configuration make the head and eyes of foveate birds move?

    Science.gov (United States)

    Moore, Bret A.; Tyrrell, Luke P.; Pita, Diana; Bininda-Emonds, Olaf R. P.; Fernández-Juricic, Esteban

    2017-01-01

    Animals move their heads and eyes to compensate for movements of the body and background, search, fixate, and track objects visually. Avian saccadic head/eye movements have been shown to vary considerably between species. We tested the hypothesis that the configuration of the retina (i.e., changes in retinal ganglion cell density from the retinal periphery to the center of acute vision-fovea) would account for the inter-specific variation in avian head/eye movement behavior. We characterized retinal configuration, head movement rate, and degree of eye movement of 29 bird species with a single fovea, controlling for the effects of phylogenetic relatedness. First, we found the avian fovea is off the retinal center towards the dorso-temporal region of the retina. Second, species with a more pronounced rate of change in ganglion cell density across the retina generally showed a higher degree of eye movement and higher head movement rate likely because a smaller retinal area with relatively high visual acuity leads to greater need to move the head/eye to align this area that contains the fovea with objects of interest. Our findings have implications for anti-predator behavior, as many predator-prey interaction models assume that the sensory system of prey (and hence their behavior) varies little between species. PMID:28079062

  11. PROPERTIES OF PROLIFERATION AND DIFFERENTIATION OF NEONATAL RAT RETINAL PROGENITOR CELLS IN VITRO

    Institute of Scientific and Technical Information of China (English)

    Kang Qianyan; Liu Yong; Zhao Jianjun; Qiu Fen; Chen Xinlin; Tian Yumei; Hu Ming

    2006-01-01

    Objective To investigate the properties of proliferation and differentiation of neonatal rat retinal progenitor cells (RPCs) in vitro. Methods RPCs were isolated from neonatal SD rats neural retina and cultured in DMEM/F12+N2 with EGF and bFGF (suspension medium )or 10%FBS without EGF and bFGF (differentiation medium). The cells grew as suspended spheres or adherent monolayers, depending on different culture conditions. The neural stem cells or retinal progenitors, neurons, astrocytes, retinal ganglion cells, rod photoreceptors and the proliferating cells were evaluated with immunofluorescence analysis by Nestin or Pax6, Map2, GFAP, Thy-1, Rhodopsin and BrdU antibodies respectively. Results RPCs could propagate and differentiate in suspension or differentiation medium and express the markers of Nestin (92.86%) or Pax6 (86.75%), Map2 (38.54%), GFAP (20.93%), Thy-1 (27.66%) and Rhodopsin(13.33%)in suspension medium; however, Nestin (60.27%), Pax6 (52%), Map2 (34.94%), GFAP (38.17%), Thy-1(30.84%) and Rhodopsin (34.67%) in differentiation medium. 96.4% of the population in the neurospheres was BrdU-positive cells. The cells could spontaneously adherent forming some subspheres and retinal specific cell types. Conclusion Neonatal rat RPCs possess the high degree of proliferation and can differentiate into neurons, astrocytes, retinal ganglion cells and rod photoreceptors in vitro. There are different proportions for RPCs to differentiate into specific cell types.

  12. 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.

  13. 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 f...... 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...

  14. Retinal oximetry in patients with ischaemic retinal diseases

    DEFF Research Database (Denmark)

    Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob

    2016-01-01

    The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between...

  15. Dorzolamide increases retinal oxygen tension after branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Noergaard, Michael Hove; Bach-Holm, Daniella; Scherfig, Erik;

    2008-01-01

    To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs.......To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs....

  16. A Catalogue of Anatomical Fugitive Sheets: Cat. 1-10

    OpenAIRE

    1999-01-01

    Images Cat. 1 Cat. 2 (a) Cat. 2 (b) Cat. 2 (c) Cat. 2 (d) Cat. 2 (e) Cat. 2 (f) Cat. 3: 1 (a) Cat. 3: 1 (b) Cat. 3: 2 (a) Cat. 3: 2 (b) Cat. 4: 1 Cat. 4: 2 Cat. 6: 1 (a) Cat. 6: 1 (b) Cat. 6: 2 (a) Cat. 6: 2 (b) Cat. 7: 1 (a) Cat. 7: 1 (b) Cat. 7: 2 (a) Cat. 7: 2 (b) Cat. 8: 1 Cat. 9: 1 Cat. 9: 2 Cat. 10: 1 Cat. 10: 2

  17. Polymer optoelectronic structures for retinal prosthesis.

    Science.gov (United States)

    Gautam, Vini; Narayan, K S

    2014-01-01

    This commentary highlights the effectiveness of optoelectronic properties of polymer semiconductors based on recent results emerging from our laboratory, where these materials are explored as artificial receptors for interfacing with the visual systems. Organic semiconductors based polymer layers in contact with physiological media exhibit interesting photophysical features, which mimic certain natural photoreceptors, including those in the retina. The availability of such optoelectronic materials opens up a gateway to utilize these structures as neuronal interfaces for stimulating retinal ganglion cells. In a recently reported work entitled "A polymer optoelectronic interface provides visual cues to a blind retina," we utilized a specific configuration of a polymer semiconductor device structure to elicit neuronal activity in a blind retina upon photoexcitation. The elicited neuronal signals were found to have several features that followed the optoelectronic response of the polymer film. More importantly, the polymer-induced retinal response resembled the natural response of the retina to photoexcitation. These observations open up a promising material alternative for artificial retina applications.

  18. Molecular Mechanisms Mediating Retinal Reactive Gliosis Following Bone Marrow Mesenchymal Stem Cell Transplantation

    OpenAIRE

    2015-01-01

    abstract A variety of diseases lead to degeneration of retinal ganglion cells (RGCs) and their axons within the optic nerve resulting in loss of visual function. Although current therapies may delay RGC loss, they do not restore visual function or completely halt disease progression. Regenerative medicine has recently focused on stem cell therapy for both neuroprotective and regenerative purposes. However, significant problems remain to be addressed, such as the long‐term impact of reactive g...

  19. 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

    Objective. 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). Approach. 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. Main results. 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. Significance. 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

  20. High Accuracy Decoding of Dynamical Motion from a Large Retinal Population.

    Directory of Open Access Journals (Sweden)

    Olivier Marre

    2015-07-01

    Full Text Available Motion tracking is a challenge the visual system has to solve by reading out the retinal population. It is still unclear how the information from different neurons can be combined together to estimate the position of an object. Here we recorded a large population of ganglion cells in a dense patch of salamander and guinea pig retinas while displaying a bar moving diffusively. We show that the bar's position can be reconstructed from retinal activity with a precision in the hyperacuity regime using a linear decoder acting on 100+ cells. We then took advantage of this unprecedented precision to explore the spatial structure of the retina's population code. The classical view would have suggested that the firing rates of the cells form a moving hill of activity tracking the bar's position. Instead, we found that most ganglion cells in the salamander fired sparsely and idiosyncratically, so that their neural image did not track the bar. Furthermore, ganglion cell activity spanned an area much larger than predicted by their receptive fields, with cells coding for motion far in their surround. As a result, population redundancy was high, and we could find multiple, disjoint subsets of neurons that encoded the trajectory with high precision. This organization allows for diverse collections of ganglion cells to represent high-accuracy motion information in a form easily read out by downstream neural circuits.

  1. Ganglion cell like cells, diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Anand Shankar Ammanagi

    2013-01-01

    Full Text Available We report a case of cutaneous swelling found on the left anterior axillary fold of a 41-year-old man. Gross examination of specimen excised from the dermis showed a well-circumscribed nodule histologically composed of spindle cells with interspersed ganglion cell like cells. On hematoxylin and eosine (H and E staining it was diagnosed as ganglioneuroma. Ganglioneuromas are rare, benign, fully differentiated tumors that contain mature schwann cells, ganglion cells, fibrous tissue, and nerve fibers. They are commonly found along the paravertebral sympathetic ganglia and sometimes in the adrenal medulla. However primary cutaneous ganglioneuroma is an extremely rare tumor. Immunohistochemical workup revealed a fibroblastic origin and hence the case was diagnosed as fibromatosis with ganglion cell like fibroblasts. This case report suggests that the features considered diagnostic of ganglioneuromas can occur in other cutaneous lesions and, therefore, this diagnosis cannot be offered only on the basis of H and E.

  2. Molecular Mechanisms Mediating Retinal Reactive Gliosis Following Bone Marrow Mesenchymal Stem Cell Transplantation.

    Science.gov (United States)

    Tassoni, Alessia; Gutteridge, Alex; Barber, Amanda C; Osborne, Andrew; Martin, Keith R

    2015-10-01

    A variety of diseases lead to degeneration of retinal ganglion cells (RGCs) and their axons within the optic nerve resulting in loss of visual function. Although current therapies may delay RGC loss, they do not restore visual function or completely halt disease progression. Regenerative medicine has recently focused on stem cell therapy for both neuroprotective and regenerative purposes. However, significant problems remain to be addressed, such as the long-term impact of reactive gliosis occurring in the host retina in response to transplanted stem cells. The aim of this work was to investigate retinal glial responses to intravitreally transplanted bone marrow mesenchymal stem cells (BM-MSCs) to help identify factors able to modulate graft-induced reactive gliosis. We found in vivo that intravitreal BM-MSC transplantation is associated with gliosis-mediated retinal folding, upregulation of intermediate filaments, and recruitment of macrophages. These responses were accompanied by significant JAK/STAT3 and MAPK (ERK1/2 and JNK) cascade activation in retinal Muller glia. Lipocalin-2 (Lcn-2) was identified as a potential new indicator of graft-induced reactive gliosis. Pharmacological inhibition of STAT3 in BM-MSC cocultured retinal explants successfully reduced glial fibrillary acidic protein expression in retinal Muller glia and increased BM-MSC retinal engraftment. Inhibition of stem cell-induced reactive gliosis is critical for successful transplantation-based strategies for neuroprotection, replacement, and regeneration of the optic nerve.

  3. A Catalogue of Anatomical Fugitive Sheets: Cat. 11-25

    OpenAIRE

    1999-01-01

    Images Cat. 11 (a) Cat. 11 (b) Cat. 11 (c) Cat. 11 (d) Cat. 12: 1 (a) Cat. 12: 1 (b) Cat. 12: 2 (a) Cat. 12: 2 (b) Cat. 13 Cat. 14 (a) Cat. 14 (b) Cat. 14 (c) Cat. 15 (a) Cat. 15 (b) Cat. 17: 1 Cat. 17: 2 Cat. 18: 1 Cat. 18: 2 Cat. 19: 1 (a) Cat. 19: 1 (b) Cat. 19: 2 (a) Cat. 19: 2 (b) Cat. 20: 1 Cat. 20: 2 (a) Cat. 20: 2 (b) Cat. 21 (a) Cat. 21 (b) Cat. 21 (c) Cat. 21 (d) Cat. 21 (e) Cat. 22 Cat. 24: 1 and 2 Cat. 25: 1 Cat. 25: 2 Cat. 25: 3 Cat. 25: 4

  4. Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis

    Institute of Scientific and Technical Information of China (English)

    Shuyi Chen; Hua Li; Karin Gaudenz; Ariel Paulson; Fengli Guo; Rhonda Trimble; Allison Peak

    2013-01-01

    The optic fissure (OF) is a transient opening on the ventral side of the developing vertebrate eye that closes before nearly all retinal progenitor cell differentiation has occurred.Failure to close the OF results in coloboma,a congenital disease that is a major cause of childhood blindness.Although human genetic studies and animal models have linked a number of genes to coloboma,the cellular and molecular mechanisms driving the closure of the OF are still largely unclear.In this study,we used Cre-LoxP-mediated conditional removal of fibroblast growth factor (FGF) receptors,Fgfr1 and Fgfr2,from the developing optic cup (OC) to show that FGF signaling regulates the closing of the OF.Our molecular,cellular and transcriptome analyses of Fgfr1 and Fgfr2 double conditional knockout OCs suggest that FGF signaling controls the OF closure through modulation of retinal progenitor cell proliferation,fate specification and morphological changes.Furthermore,Fgfr1 and Fgfr2 double conditional mutant retinal progenitor cells fail to initiate retinal ganglion cell (RGC) genesis.Taken together,our mouse genetic studies reveal that FGF signaling is essential for OF morphogenesis and RGC development.

  5. Cat scratch encephalopathy.

    Science.gov (United States)

    Silver, B E; Bean, C S

    1991-06-01

    Cat scratch disease is usually benign, self-limited and without sequelae. Margileth has established four clinical criteria, three of which must be satisfied to make the diagnosis: 1) a history of animal exposure, usually kitten, with primary skin or ocular lesions; 2) regional chronic adenopathy without other apparent cause; 3) a positive cat scratch disease antigen skin test; and 4) lymph node biopsy demonstrating noncaseating granulomas and germinal center hyperplasia. Central nervous system involvement in cat scratch disease has been previously reported, although it is extremely uncommon. In a several-month period, we encountered two cases of cat scratch disease complicated by encephalopathy. The intents of this paper are twofold: 1) to briefly review the current literature on cat scratch disease, 2) to demonstrate that cat scratch disease complicated by encephalopathy presents acutely with seizures, posturing and coma and resolves rapidly with supportive care.

  6. Diverse Clinical Signs of Ocular Involvement in Cat Scratch Disease

    Science.gov (United States)

    Oray, Merih; Önal, Sumru; Koç Akbay, Aylin; Tuğal Tutkun, İlknur

    2017-01-01

    Objectives: To describe ocular manifestations, diagnosis, and treatment of cat scratch disease. Materials and Methods: Clinical records of patients with ocular cat scratch disease were reviewed. Results: Thirteen eyes of 10 patients (7 female, 3 male) with a mean age of 26.9±18.5 years were included. Nine patients had a history of cat contact and had systemic symptoms associated with cat scratch disease 2-90 days prior to the ocular symptoms. Ocular signs were: neuroretinitis in 4 eyes (associated with serous retinal detachment in the inferior quadrant in 1 eye), optic neuropathy in 2 eyes (1 papillitis and optic disc infiltration, 1 optic neuritis), retinal infiltrates in 6 eyes, retinochoroiditis in 1 eye, branch retinal arteriolar occlusion in 3 eyes, and endophthalmitis in 1 eye. Visual acuities at presentation were 1.0 in 7 eyes, 0.3 in 1 eye, ≤0.1 in 4 eyes, and light perception in 1 eye. Bartonella henselae immunoglobulin (Ig) M and/or IgG were positive in all patients. Systemic antibiotic therapy was administered in all patients. Systemic corticosteroid treatment (15-40 mg/day) was added to the therapy in 4 patients, following 5 days of intravenous pulse methylprednisolone in 2 patients. Treatment was ongoing for 1 patient and the mean treatment duration of the other 9 patients was 47±14.5 days. Visual acuities at final visit were 1.0 in 9 eyes, 0.8 in 1 eye, 0.4 in 1 eye, and no light perception in 1 eye. Conclusion: Cat scratch disease may present with different ocular signs and should be considered in the differential diagnosis in patients with such presentations. PMID:28182175

  7. Characterization of Progenitor Cells during Canine Retinal Development

    Directory of Open Access Journals (Sweden)

    Mallely Ávila-García

    2012-01-01

    Full Text Available We identify the presence of progenitor cells during retinal development in the dog, as this species represents a natural model for studying several breed-specific degenerative retinal disorders. Antibodies to detected progenitor cells (Pax6, C-kit, and nestin and ganglion cells (BDNF, Brn3a, and Thy1 were used in combination with H3 for the purpose of identifying proliferating cells. Pax6, nestin, C-kit, and H3 were localized mainly in the neuroblastic layer of the retina during the embryonic stage. During the fetal stage, proteins were expressed in the inner neuroblastic layer (INL as well as in the outer neuroblastic layer; BDNF, Thy1, and Brn3a were also expressed in the INL. During the neonatal stage only C-kit was not expressed. Proliferating cells were present in both undifferentiated and differentiated retina. These results suggest that, during canine retinogenesis, progenitor cells are distributed along the retina and some of these cells remain as progenitor cells of the ganglion cells during the first postnatal days.

  8. Genotype-phenotype heterogeneity of ganglion cell and inner plexiform layer deficit in autosomal-dominant optic atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Nissen, Claus; Almind, Gitte J;

    2015-01-01

    PURPOSE: To describe the thickness of the combined ganglion cell and inner plexiform layers (GC-IPL) and the peripapillary retinal nerve fibre layer (RNFL) in patients with OPA1 c.983A>G or c.2708_2711delTTAG autosomal-dominant optic atrophy (ADOA). METHODS: The study included 20 individuals with c...... measurement and high-definition optical coherence tomography. RESULTS: There was overlap in GC-IPL thickness in subjects younger than 20-30 years between the two new groups of ADOA patients and controls. Numerical decreases in GC-IPL thickness with age did not reach statistical significance in individuals...

  9. 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

    2012-04-01

    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.

  10. Cat-scratch disease

    Science.gov (United States)

    ... scratch or bite from a cat, your health care provider may suspect cat-scratch disease. A physical examination may also reveal an enlarged spleen . Sometimes, an infected lymph node may form a tunnel ( fistula ) through the skin and drain (leak fluid). This ...

  11. Hyperadrenocorticism in a cat.

    Science.gov (United States)

    Zerbe, C A; Nachreiner, R F; Dunstan, R W; Dalley, J B

    1987-03-01

    A diabetic cat with hyperadrenocorticism had polydipsia, polyuria, ventral abdominal alopecia, thin dry skin, and a pendulous abdomen. Results of laboratory testing indicated persistent resting hypercortisolemia, hyperresponsiveness of the adrenal glands (increased cortisol concentration) to ACTH gel, and no suppression of cortisol concentrations after administration of dexamethasone at 0.01 or 1.0 mg/kg of body weight. Necropsy revealed a pituitary gland tumor, bilateral adrenal hyperplasia, hepatic neoplasia, and demodicosis. Adrenal gland function was concurrently assessed in 2 cats with diabetes mellitus. One cat had resting hypercortisolemia, and both had hyperresponsiveness to ACTH gel (increased cortisol concentration) at one hour. After administration of dexamethasone (0.01 and 1.0 mg/kg), the diabetic cats appeared to have normal suppression of cortisol concentrations. The effects of mitotane were investigated in 4 clinically normal cats. Adrenocortical suppression of cortisol production occurred in 2 of 4 cats after dosages of 25, 37, and 50 mg/kg. Three cats remained clinically normal throughout the study. One cat experienced vomiting, diarrhea, and anorexia.

  12. Cat-Scratch Disease

    Science.gov (United States)

    ... bites and scratches well with soap and running water. Do not allow cats to lick your wounds. Contact your doctor if you develop any symptoms of cat-scratch disease or infection. CSD is caused by a bacterium called Bartonella henselae . About 40% ...

  13. That Fat Cat

    Science.gov (United States)

    Lambert, Phyllis Gilchrist

    2012-01-01

    This activity began with a picture book, Nurit Karlin's "Fat Cat On a Mat" (HarperCollins; 1998). The author and her students started their project with a 5-inch circular template for the head of their cats. They reviewed shapes as they drew the head and then added the ears and nose, which were triangles. Details to the face were added when…

  14. Cat scratch colon.

    Science.gov (United States)

    Ruiz-Rebollo, M Lourdes; Velayos-Jiménez, Benito; Prieto de Paula, José María; Alvarez Quiñones, María; González Hernández, José Manuel

    2011-01-01

    Over the past few years, we have read several publications regarding the term "cat scratch colon." This neologism was developed to define some bright red linear markings seen in the colonic mucosa that resemble scratches made by a cat. We would like to communicate a recent case attended at our institution.

  15. Cat Scratch Colon

    Directory of Open Access Journals (Sweden)

    M. Lourdes Ruiz-Rebollo

    2011-01-01

    Full Text Available Over the past few years, we have read several publications regarding the term “cat scratch colon.” This neologism was developed to define some bright red linear markings seen in the colonic mucosa that resemble scratches made by a cat. We would like to communicate a recent case attended at our institution.

  16. State of cat genomics.

    Science.gov (United States)

    O'Brien, Stephen J; Johnson, Warren; Driscoll, Carlos; Pontius, Joan; Pecon-Slattery, Jill; Menotti-Raymond, Marilyn

    2008-06-01

    Our knowledge of cat family biology was recently expanded to include a genomics perspective with the completion of a draft whole genome sequence of an Abyssinian cat. The utility of the new genome information has been demonstrated by applications ranging from disease gene discovery and comparative genomics to species conservation. Patterns of genomic organization among cats and inbred domestic cat breeds have illuminated our view of domestication, revealing linkage disequilibrium tracks consequent of breed formation, defining chromosome exchanges that punctuated major lineages of mammals and suggesting ancestral continental migration events that led to 37 modern species of Felidae. We review these recent advances here. As the genome resources develop, the cat is poised to make a major contribution to many areas in genetics and biology.

  17. 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.

  18. Comparative study of aural microflora in healthy cats, allergic cats and cats with systemic disease.

    Science.gov (United States)

    Pressanti, Charline; Drouet, Clémence; Cadiergues, Marie-Christine

    2014-12-01

    Twenty healthy cats (group 1) with clinically normal ears, 15 cats with systemic disease (group 2) and 15 allergic cats (group 3) were included in a prospective study. The experimental unit was the ear. A clinical score was established for each ear canal after otoscopic examination. Microbial population was assessed on cytological examination of smears performed with the cotton-tipped applicator smear technique. Fungal population was significantly more prominent in allergic cats (P cats compared with healthy cats (P cats than in healthy cats (P cats suffering from systemic disease (P cats with systemic disease than healthy cats. In cats from group 2, only fungal overgrowth was associated with otitis severity. In group 3, only bacterial overgrowth was associated with otitis severity.

  19. Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Relevance to Leber Hereditary Optic Neuropathy (LHON).

    Science.gov (United States)

    Beretta, Simone; Wood, John P M; Derham, Barry; Sala, Gessica; Tremolizzo, Lucio; Ferrarese, Carlo; Osborne, Neville N

    2006-11-01

    Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the pathophysiology of this disorder remains obscure. Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition. Neural cells were more sensitive than Müller glial cells to rotenone toxicity. Rotenone induced an increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium-dependent glutamate uptake, which is mostly mediated by the glutamate transporter GLAST expressed by Müller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex I-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON.

  20. Optical Coherence Tomography Reveals Distinct Patterns of Retinal Damage in Neuromyelitis Optica and Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Elisa Schneider

    Full Text Available Neuromyelitis optica (NMO and relapsing-remitting multiple sclerosis (RRMS are difficult to differentiate solely on clinical grounds. Optical coherence tomography (OCT studies investigating retinal changes in both diseases focused primarily on the retinal nerve fiber layer (RNFL while rare data are available on deeper intra-retinal layers.To detect different patterns of intra-retinal layer alterations in patients with NMO spectrum disorders (NMOSD and RRMS with focus on the influence of a previous optic neuritis (ON.We applied spectral-domain OCT in eyes of NMOSD patients and compared them to matched RRMS patients and healthy controls (HC. Semi-automatic intra-retinal layer segmentation was used to quantify intra-retinal layer thicknesses. In a subgroup low contrast visual acuity (LCVA was assessed.NMOSD-, MS- and HC-groups, each comprising 17 subjects, were included in analysis. RNFL thickness was more severely reduced in NMOSD compared to MS following ON. In MS-ON eyes, RNFL thinning showed a clear temporal preponderance, whereas in NMOSD-ON eyes RNFL was more evenly reduced, resulting in a significantly lower ratio of the nasal versus temporal RNFL thickness. In comparison to HC, ganglion cell layer thickness was stronger reduced in NMOSD-ON than in MS-ON, accompanied by a more severe impairment of LCVA. The inner nuclear layer and the outer retinal layers were thicker in NMOSD-ON patients compared to NMOSD without ON and HC eyes while these differences were primarily driven by microcystic macular edema.Our study supports previous findings that ON in NMOSD leads to more pronounced retinal thinning and visual function impairment than in RRMS. The different retinal damage patterns in NMOSD versus RRMS support the current notion of distinct pathomechanisms of both conditions. However, OCT is still insufficient to help with the clinically relevant differentiation of both conditions in an individual patient.

  1. Adenosine A3 receptor activation is neuroprotective against retinal neurodegeneration.

    Science.gov (United States)

    Galvao, Joana; Elvas, Filipe; Martins, Tiago; Cordeiro, M Francesca; Ambrósio, António Francisco; Santiago, Ana Raquel

    2015-11-01

    Death of retinal neural cells, namely retinal ganglion cells (RGCs), is a characteristic of several retinal neurodegenerative diseases. Although the role of adenosine A3 receptor (A3R) in neuroprotection is controversial, A3R activation has been reported to afford protection against several brain insults, with few studies in the retina. In vitro models (retinal neural and organotypic cultures) and animal models [ischemia-reperfusion (I-R) and partial optic nerve transection (pONT)] were used to study the neuroprotective properties of A3R activation against retinal neurodegeneration. The A3R selective agonist (2-Cl-IB-MECA, 1 μM) prevented apoptosis (TUNEL(+)-cells) induced by kainate and cyclothiazide (KA + CTZ) in retinal neural cultures (86.5 ± 7.4 and 37.2 ± 6.1 TUNEL(+)-cells/field, in KA + CTZ and KA + CTZ + 2-Cl-IB-MECA, respectively). In retinal organotypic cultures, 2-Cl-IB-MECA attenuated NMDA-induced cell death, assessed by TUNEL (17.3 ± 2.3 and 8.3 ± 1.2 TUNEL(+)-cells/mm(2) in NMDA and NMDA+2-Cl-IB-MECA, respectively) and PI incorporation (ratio DIV4/DIV2 3.3 ± 0.3 and 1.3 ± 0.1 in NMDA and NMDA+2-Cl-IB-MECA, respectively) assays. Intravitreal 2-Cl-IB-MECA administration afforded protection against I-R injury decreasing the number of TUNEL(+) cells by 72%, and increased RGC survival by 57%. Also, intravitreal administration of 2-Cl-IB-MECA inhibited apoptosis (from 449.4 ± 37.8 to 207.6 ± 48.9 annexin-V(+)-cells) and RGC loss (from 1.2 ± 0.6 to 8.1 ± 1.7 cells/mm) induced by pONT. This study demonstrates that 2-Cl-IB-MECA is neuroprotective to the retina, both in vitro and in vivo. Activation of A3R may have great potential in the management of retinal neurodegenerative diseases characterized by RGC death, as glaucoma and diabetic retinopathy, and ischemic diseases.

  2. Heterochronic misexpression of Ascl1 in the Atoh7 retinal cell lineage blocks cell cycle exit.

    Science.gov (United States)

    Hufnagel, Robert B; Riesenberg, Amy N; Quinn, Malgorzata; Brzezinski, Joseph A; Glaser, Tom; Brown, Nadean L

    2013-05-01

    Retinal neurons and glia arise from a common progenitor pool in a temporal order, with retinal ganglion cells (RGCs) appearing first, and Müller glia last. The transcription factors Atoh7/Math5 and Ascl1/Mash1 represent divergent bHLH clades, and exhibit distinct spatial and temporal retinal expression patterns, with little overlap during early development. Here, we tested the ability of Ascl1 to change the fate of cells in the Atoh7 lineage when misexpressed from the Atoh7 locus, using an Ascl1-IRES-DsRed2 knock-in allele. In Atoh7(Ascl1KI/+) and Atoh7(Ascl1KI/Ascl1KI) embryos, ectopic Ascl1 delayed cell cycle exit and differentiation, even in cells coexpressing Atoh7. The heterozygous retinas recovered, and eventually produced a normal complement of RGCs, while homozygous substitution of Ascl1 for Atoh7 did not promote postnatal retinal fates precociously, nor rescue Atoh7 mutant phenotypes. However, our analyses revealed two unexpected findings. First, ectopic Ascl1 disrupted cell cycle progression within the marked Atoh7 lineage, but also nonautonomously in other retinal cells. Second, the size of the Atoh7 retinal lineage was unaffected, supporting the idea of a compensatory shift of the non-proliferative cohort to maintain lineage size. Overall, we conclude that Ascl1 acts dominantly to block cell cycle exit, but is incapable of redirecting the fates of early RPCs.

  3. 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.

  4. Giardia infection in cats.

    Science.gov (United States)

    Janeczko, Stephanie; Griffin, Brenda

    2010-08-01

    The protozoon Giardia duodenalis is a common gastrointestinal parasite of cats. While most Giardia-infected cats are asymptomatic, acute small bowel diarrhea, occasionally with concomitant weight loss, may occur. Giardia poses a diagnostic challenge, but newer tests, including a commercially available ELISA kit, have improved clinicians' ability to obtain an accurate diagnosis. Several treatment options have been reported, and although none has been shown to be universally effective, most cases can be successfully managed with drug therapy, supportive measures, and environmental control. Current recommendations suggest that combination therapy with fenbendazole and metronidazole may be the safest, most effective treatment option for symptomatic cats.

  5. 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.

  6. Probabilistic retinal vessel segmentation

    Science.gov (United States)

    Wu, Chang-Hua; Agam, Gady

    2007-03-01

    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  7. 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.

  8. Evidence for a blood-ganglion barrier in the superior cervical ganglion of the rat.

    Science.gov (United States)

    Depace, D M

    1982-12-01

    The permeability of the blood vessels in the superior cervical ganglion of the rat was tested by intravenous injection of horseradish peroxidase (HRP). By light microscopy, peroxidase activity was found in three locations: in the capsule of the ganglion, in the lumina of the blood vessels, and within macrophages. Electron microscopy revealed that virtually all ganglionic blood vessels contained HRP 5 minutes following its administration. The intensity of peroxidase activity declined over the period of 15 minutes. The enzyme was localized on the luminal surface of the endothelial cells, attaching to the glycocalyx. Endothelial microvilli, projecting into the vessel lumen, were also covered with peroxidase. Micropinocytotic vesicles on the luminal surface of the endothelium contained reaction product. Some of these vesicles were free within the cytoplasm of the endothelium but none was observed on the abluminal surface. Peroxidase activity was not detected in the extracellular space even after 15 minutes. The majority of blood vessels in the superior cervical ganglion possess a continuous endothelium with tight junctions; features associated with the blood-brain barrier of the central nervous system and peripheral nerves. It is proposed that these vessels perform a barrier function between the capillary circulation and the superior cervical ganglion.

  9. 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.

  10. Endoscopic sphenopalatine ganglion block for pain relief

    OpenAIRE

    Murty, P. S. N.; Prasanna, Atma

    1998-01-01

    The anaesthetic effect of the sphenopalatine (SPG) block has been well utilized for intranasal topical anaesthesia but the analgesic efficacy of (SPG) block, though well documented in literature, has not been put into practice. The methods available for SPG block till date were blind as they do not visualize the foramen. Nasal endoscopies have been used to visualize the foramen for an effective block. The authors present their experience with the endoscopic sphenopalatine ganglion block for p...

  11. Retinal flow cytometer.

    Science.gov (United States)

    Alt, C; Veilleux, I; Lee, H; Pitsillides, C M; Côté, D; Lin, C P

    2007-12-01

    The in vivo flow cytometer is an instrument capable of continuous, real-time monitoring of fluorescently labeled cells in the circulation without the need to draw blood samples. However, the original system probes a single vessel in the mouse ear; the small sample volume limits the sensitivity of the technique. We describe an in vivo retinal flow cytometer that simultaneously probes five artery-vein pairs in the mouse eye by circularly scanning a small laser spot rapidly around the optic nerve head. We demonstrate that the retinal flow cytometer detects about five times more cells per minute than the original in vivo flow cytometer does in the ear.

  12. Visual Capability of the Weakly Electric Fish Apteronotus albifrons as Revealed by a Modified Retinal Flat-Mount Method.

    Science.gov (United States)

    Takiyama, Tomo; Luna da Silva, Valdir; Moura Silva, Daniel; Hamasaki, Sawako; Yoshida, Masayuki

    2015-01-01

    Apteronotus albifrons (Gymnotiformes, Apteronotidae) is well known to have a sophisticated active electrosense system and is commonly described as having poor vision or being almost blind. However, some studies on this species suggest that the visual system may have a role in sensing objects in the environment. In this study, we investigated the visual capabilities of A. albifrons by focusing on eye morphology and retinal ganglion cell distribution. The eyes were almost embedded below the body surface and pigmented dermal tissue covered the peripheral regions of the pupil, limiting the direction of incoming light. The lens was remarkably flattened compared to the almost spherical lenses of other teleosts. The layered structure of the retina was not well delineated and ganglion cells did not form a continuous sheet of cell bodies. A newly modified retinal flat-mount method was applied to reveal the ganglion cell distribution. This method involved postembedding removal of the pigment epithelium of the retina for easier visualization of ganglion cells in small and/or fragile retinal tissues. We found that ganglion cell densities were relatively high in the periphery and highest in the nasal and temporal retina, although specialization was not so high (approx. 3:1) with regard to the medionasal or mediotemporal axis. The estimated highest possible spatial resolving power was around 0.57 and 0.54 cycles/degree in the nasal and temporal retina, respectively, confirming the lower importance of the visual sense in this species. However, considering the hunting nature of A. albifrons, the relatively high acuity of the caudal visual field in combination with electrolocation may well be used to locate prey situated close to the side of the body.

  13. Thalamic pain alleviated by stellate ganglion block

    Science.gov (United States)

    Liao, Chenlong; Yang, Min; Liu, Pengfei; Zhong, Wenxiang; Zhang, Wenchuan

    2017-01-01

    Abstract Rationale: Thalamic pain is a distressing and treatment-resistant type of central post-stroke pain. Although stellate ganglion block is an established intervention used in pain management, its use in the treatment of thalamic pain has never been reported. Patient concerns: A 66-year-old woman presented with a 3-year history of severe intermittent lancinating pain on the right side of the face and the right hand. The pain started from the ulnar side of the right forearm after a mild ischemic stroke in bilateral basal ganglia and left thalamus. Weeks later, the pain extended to the dorsum of the finger tips and the whole palmar surface, becoming more severe. Meanwhile, there was also pain with similar characteristics emerging on her right face, resembling atypical trigeminal neuralgia. Diagnoses: Thalamic pain was diagnosed. Interventions: After refusing the further invasive treatment, she was suggested to try stellate ganglion block. Outcomes: After a 3-day period of pain free (numerical rating scale: 0) postoperatively, she reported moderate to good pain relief with a numerical rating scale of about 3 to 4 lasting 1 month after the first injection. Pain as well as the quality of life was markedly improved with less dose of analgesic agents. Lessons: Stellate ganglion block may be an optional treatment for thalamic pain. PMID:28151918

  14. StreamCat

    Data.gov (United States)

    U.S. Environmental Protection Agency — The StreamCat Dataset provides summaries of natural and anthropogenic landscape features for ~2.65 million streams, and their associated catchments, within the...

  15. IndexCat

    Data.gov (United States)

    U.S. Department of Health & Human Services — IndexCat provides access to the digitized version of the printed Index-Catalogue of the Library of the Surgeon General's Office; eTK for medieval Latin texts; and...

  16. Cat tongue Velcro

    Science.gov (United States)

    Noel, Alexis; Martinez, Andrea; Jung, Hyewon; Tsai, Ting-Wen; Hu, David

    2016-11-01

    A cat's tongue is covered in an array of spines called papillae. These spines are thought to be used in grooming and rasping meat from bones of prey, although no mechanism has been given. We use high-speed video to film a cat removing cat food deeply wedged into a 3-D printed fur mat. We show that the spines on the tongue act as Velcro for particles. The tongue itself is highly elastic. As the cat presses it against a substrate, the tongue flattens and the spines separate. When the tongue is removed from the substrate the spines come together, wedging particles between them. This elasticity-driven entrapment permits the surface of the tongue to act as a carrier for hard to reach particles, and to increase the efficacy of grooming and feeding.

  17. Retinal architecture and mfERG

    Science.gov (United States)

    Schnurman, Zane S.; Frohman, Teresa C.; Beh, Shin C.; Conger, Darrel; Conger, Amy; Saidha, Shiv; Galetta, Steven; Calabresi, Peter A.; Green, Ari J.

    2014-01-01

    Objective: To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. Methods: We used multifocal electroretinogram–generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential–induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography. Results: Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-μm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001). Conclusion: Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular. PMID:24789865

  18. Processing of single-photon responses in the mammalian On and Off retinal pathways at the sensitivity limit of vision

    Science.gov (United States)

    2017-01-01

    Visually guided behaviour at its sensitivity limit relies on single-photon responses originating in a small number of rod photoreceptors. For decades, researchers have debated the neural mechanisms and noise sources that underlie this striking sensitivity. To address this question, we need to understand the constraints arising from the retinal output signals provided by distinct retinal ganglion cell types. It has recently been shown in the primate retina that On and Off parasol ganglion cells, the cell types likely to underlie light detection at the absolute visual threshold, differ fundamentally not only in response polarity, but also in the way they handle single-photon responses originating in rods. The On pathway provides the brain with a thresholded, low-noise readout and the Off pathway with a noisy, linear readout. We outline the mechanistic basis of these different coding strategies and analyse their implications for detecting the weakest light signals. We show that high-fidelity, nonlinear signal processing in the On pathway comes with costs: more single-photon responses are lost and their propagation is delayed compared with the Off pathway. On the other hand, the responses of On ganglion cells allow better intensity discrimination compared with the Off ganglion cell responses near visual threshold. This article is part of the themed issue ‘Vision in dim light’. PMID:28193818

  19. Retinal locus for scanning text.

    Science.gov (United States)

    Timberlake, George T; Sharma, Manoj K; Grose, Susan A; Maino, Joseph H

    2006-01-01

    A method of mapping the retinal location of text during reading is described in which text position is plotted cumulatively on scanning laser ophthalmoscope retinal images. Retinal locations that contain text most often are the brightest in the cumulative plot, and locations that contain text least often are the darkest. In this way, the retinal area that most often contains text is determined. Text maps were plotted for eight control subjects without vision loss and eight subjects with central scotomas from macular degeneration. Control subjects' text maps showed that the fovea contained text most often. Text maps of five of the subjects with scotomas showed that they used the same peripheral retinal area to scan text and fixate. Text maps of the other three subjects with scotomas showed that they used separate areas to scan text and fixate. Retinal text maps may help evaluate rehabilitative strategies for training individuals with central scotomas to use a particular retinal area to scan text.

  20. Learning about Retinitis Pigmentosa

    Science.gov (United States)

    ... that detect light). Photoreceptor cells capture and process light helping us to see. As these cells breakdown and die, patients experience progressive vision loss. The most common feature of all forms of RP is a ... cells that detect dim light) and cones (retinal cells that detect light and ...

  1. Retinal vein occlusion

    Science.gov (United States)

    ... decrease the risk of retinal vein occlusion. These measures include: Eating a low-fat diet Getting regular exercise Maintaining an ideal weight Not smoking Aspirin or other blood thinners may help prevent blockages in the other eye. Controlling diabetes may ...

  2. 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...

  3. Effect of age and sex on retinal layer thickness and volume in normal eyes.

    Science.gov (United States)

    Won, Jae Yon; Kim, Sung Eun; Park, Young-Hoon

    2016-11-01

    The aim of the study was to evaluate the effect of sex and age on the thickness of the retinal layer in normal eyes using spectral-domain optical coherence tomography (SD-OCT).Fifty healthy subjects between the ages of 20 and 80 had their retinal layers measured using SD-OCT at Seoul St. Mary's Hospital. Mean thickness and volume were measured for 9 retinal layers in the fovea, the pericentral ring, and the peripheral ring. The differences of sex- and age-related thickness and volume in each retinal layer were analyzed.The retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL) were thinnest in the fovea area, whereas the outer nuclear layer (ONL), photoreceptor layer (PHL), and retinal pigment epithelium (RPE) were thickest at similar locations. Mean thickness of the RNFL, GCL, IPL, and OPL was significantly greater in men than women. However, mean thickness of the ONL was greater in women than in men. When compared between patients 60 years of age, the thickness and volume of peripheral RNFL, GCL, and pericentral and peripheral IPL were significantly larger in the younger group than the older group. Conversely, the thickness and volume of foveal INL and IR were larger in the older group than in the younger group.The thickness and volume of the retinal layer in normal eyes significantly vary depending on age and sex. These results should be considered when evaluating layer analysis in retinal disease.

  4. Quantitative genetic analysis of retinal degeneration in the blind cavefish Astyanax mexicanus.

    Directory of Open Access Journals (Sweden)

    Kelly E O'Quin

    Full Text Available The retina is the light-sensitive tissue of the eye that facilitates vision. Mutations within genes affecting eye development and retinal function cause a host of degenerative visual diseases, including retinitis pigmentosa and anophthalmia/microphthalmia. The characin fish Astyanax mexicanus includes both eyed (surface fish and eyeless (cavefish morphs that initially develop eyes with normal retina; however, early in development, the eyes of cavefish degenerate. Since both surface and cave morphs are members of the same species, they serve as excellent evolutionary mutant models with which to identify genes causing retinal degeneration. In this study, we crossed the eyed and eyeless forms of A. mexicanus and quantified the thickness of individual retinal layers among 115 F(2 hybrid progeny. We used next generation sequencing (RAD-seq and microsatellite mapping to construct a dense genetic map of the Astyanax genome, scan for quantitative trait loci (QTL affecting retinal thickness, and identify candidate genes within these QTL regions. The map we constructed for Astyanax includes nearly 700 markers assembled into 25 linkage groups. Based on our scans with this map, we identified four QTL, one each associated with the thickness of the ganglion, inner nuclear, outer plexiform, and outer nuclear layers of the retina. For all but one QTL, cavefish alleles resulted in a clear reduction in the thickness of the affected layer. Comparative mapping of genetic markers within each QTL revealed that each QTL corresponds to an approximately 35 Mb region of the zebrafish genome. Within each region, we identified several candidate genes associated with the function of each affected retinal layer. Our study is the first to examine Astyanax retinal degeneration in the context of QTL mapping. The regions we identify serve as a starting point for future studies on the genetics of retinal degeneration and eye disease using the evolutionary mutant model Astyanax.

  5. Matrix metalloproteinase 14 in the zebrafish: an eye on retinal and retinotectal development.

    Directory of Open Access Journals (Sweden)

    Els Janssens

    Full Text Available BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.

  6. Duration of rhegmatogenous retinal detachment predicts recovery of retinal sensitivity

    Directory of Open Access Journals (Sweden)

    Rose Rose

    2016-02-01

    Full Text Available The decision to treat a disease is often based on the presence or absence of symptoms, one prototype case being rhegmatogenous retinal detachment. Detachment of the neural retina from the pigment epithelium is a major cause of anatomical and functional dysfunction of the retina, where retinal recovery is inversely related to duration of detachment. The purpose of retinal reattachment is to effect recovery of the photoreceptors and pigment epithelium from degeneration. The aim of this study was to determine the critical duration of rhegmatogenous retinal detachment resulting in optimal retinal recovery after reattachment. A prospective study was conducted at a private hospital in Yogyakarta. Thirty five eyes were involved in this study. Three months after reattachment, central retinal recovery was measured by means of a Goldmann manual kinetic perimeter. The results showed that retinal recovery developed three months after surgery if the onset of rhegmatogenous retinal detachment was less than 28 days before surgery. The results were not significant if the onset of rhegmatogenous retinal detachment was more than 35 days. Although the Goldmann manual kinetic perimeter can efficiently detect central retinal sensitivity, it should be supported by more sensitive tools to evaluate the anatomy and function of the retina.

  7. 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.

  8. Aldose reductase mediates retinal microglia activation.

    Science.gov (United States)

    Chang, Kun-Che; Shieh, Biehuoy; Petrash, J Mark

    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(GFP) mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migration in vivo. When tested on an AR(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.

  9. Peripapillary retinal thermal coagulation following electrical injury

    Directory of Open Access Journals (Sweden)

    Manjari Tandon

    2013-01-01

    Full Text Available In this study, we have presented the case report of a 20 year old boy who suffered an electric injury shock, following which he showed peripapillary retinal opacification and increased retinal thickening that subsequently progressed to retinal atrophy. The fluorescein angiogram revealed normal retinal circulation, thus indicating thermal damage to retina without any compromise to retinal circulation.

  10. Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Mansergh, Fiona C; Chadderton, Naomi; Kenna, Paul F; Gobbo, Oliviero L; Farrar, G Jane

    2014-11-01

    Primary mitochondrial disorders occur at a prevalence of one in 10 000; ∼50% of these demonstrate ocular pathology. Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial disorder. LHON results from retinal ganglion cell pathology, which leads to optic nerve degeneration and blindness. Over 95% of cases result from one of the three common mutations in mitochondrial genes MTND1, MTND4 and MTND6, which encode elements of the complex I respiratory chain. Various therapies for LHON are in development, for example, intravitreal injection of adeno-associated virus carrying either the yeast NDI1 gene or a specific subunit of mammalian Complex I have shown visual improvement in animal models. Given the course of LHON, it is likely that in many cases prompt administration may be necessary before widespread cell death. An alternative approach for therapy may be the use of stem cells to protect visual function; this has been evaluated by us in a rotenone-induced model of LHON. Freshly dissected embryonic retinal cells do not integrate into the ganglion cell layer (GCL), unlike similarly obtained photoreceptor precursors. However, cultured retinal progenitor cells can integrate in close proximity to the GCL, and act to preserve retinal function as assessed by manganese-enhanced magnetic resonance imaging, optokinetic responses and ganglion cell counts. Cell therapies for LHON therefore represent a promising therapeutic approach, and may be of particular utility in treating more advanced disease.

  11. Weak Cat-Operads

    CERN Document Server

    Dosen, K

    2010-01-01

    An operad (this paper deals with non-symmetric operads) may be conceived as a partial algebra with a family of insertion operations, Gerstenhaber's circle-i products, which satisfy two kinds of associativity, one of them involving commutativity. A Cat-operad is an operad enriched over the category Cat of small categories, as a 2-category with small hom-categories is a category enriched over Cat. The notion of weak Cat-operad is to the notion of Cat-operad what the notion of bicategory is to the notion of 2-category. The equations of operads like associativity of insertions are replaced by isomorphisms in a category. The goal of this paper is to formulate conditions concerning these isomorphisms that ensure coherence, in the sense that all diagrams of canonical arrows commute. This is the sense in which the notions of monoidal category and bicategory are coherent. The coherence proof in the paper is much simplified by indexing the insertion operations in a context-independent way, and not in the usual manner. ...

  12. The Feline Mystique: Dispelling the Myth of the Independent Cat.

    Science.gov (United States)

    Soltow, Willow

    1984-01-01

    Describes learning activities about cats for primary and intermediate grades. Primary grade activity subjects include cat behavior, needs, breeds, storybook cats, and celestial cats. Intermediate grade activity subjects include cat history, care, language, literary cats, and cats in art. (BC)

  13. Cell-Type Specific Roles for PTEN in Establishing a Functional Retinal Architecture

    Science.gov (United States)

    Cantrup, Robert; Dixit, Rajiv; Palmesino, Elena; Bonfield, Stephan; Shaker, Tarek; Tachibana, Nobuhiko; Zinyk, Dawn; Dalesman, Sarah; Yamakawa, Kazuhiro; Stell, William K.; Wong, Rachel O.; Reese, Benjamin E.; Kania, Artur; Sauvé, Yves; Schuurmans, Carol

    2012-01-01

    Background The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. Methodology/Principal Findings In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. Conclusions/Significance We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular

  14. Cell-type specific roles for PTEN in establishing a functional retinal architecture.

    Directory of Open Access Journals (Sweden)

    Robert Cantrup

    Full Text Available BACKGROUND: The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. METHODOLOGY/PRINCIPAL FINDINGS: In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. CONCLUSIONS/SIGNIFICANCE: We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected

  15. Retinal abnormalities in multiple sclerosis patients with associated chronic cerebrospinal venous insufficiency

    Directory of Open Access Journals (Sweden)

    Aneta Adamczyk-Ludyga

    2012-06-01

    Full Text Available Optical coherence tomography (OCT is a non-invasive method for the assessment of optic nerve fibers and retinal ganglion cells. This study was aimed at the assessment of retinal abnormalities in multiple sclerosis patients in the context of chronic cerebrospinal venous insufficiency using OCT of the retina and the optic nerve. We examined 239 multiple sclerosis (MS patients, including 220 patients with associated chronic cerebrospinal venous insufficiency and 19 MS patients without venous pathology. The following OCT parameters were assessed: average ganglion cell complex thickness, global loss volume, focal loss volume and average retinal nerve fibre layer thickness. Abnormalities in the azygous and internal jugular veins were evaluated using catheter venography. We found a higher prevalence of abnormal OCT parameters in the patients with previous history of optic neuritis, not only on the side of inflammatory event, but also in the contralateral eye, which is in line with already existing body of evidence. The new and intriguing discovery is that we found statistically significant higher prevalence of abnormal OCT values in multiple sclerosis patients with unilateral stenosis of internal jugular vein. Patients who were not found venous abnormalities, as well as those presenting with pathologic azygous or bilateral internal jugular venous outflows, did not demonstrate a changed frequency of abnormal OCT parameters. Potential association between venous malformations and eye manifestations of multiple sclerosis, as has been demonstrated in this report, justifies further studies on this topic.

  16. 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.

  17. Intraosseous ganglion in the first metacarpal bone

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, H.; Itoh, Tatsuo; Katoh, Y.; Munakata, Y. [Dept. of Orthopaedic Surgery, Tokyo Women' s Medical Univ. (Japan)

    2001-10-01

    Intraosseous ganglia occur most frequently in the long bones of the lower limbs, particularly in the medial malleolus of the tibia. They usually appear as radiographically well circumscribed juxta-articular cystic lesions, containing myxoid fibrous tissue histologically. Intraosseous ganglia in the hand are very rare. Most reported cases have involved the carpal bones, in particular the lunate and scaphoid. To our knowledge, the present case is the third report of an intraosseous ganglion appearing in the first metacarpal bone; it arose in a patient who had been on dialysis for 25 years, mimicking amyloidosis of bone. (orig.)

  18. KUS121, a VCP modulator, attenuates ischemic retinal cell death via suppressing endoplasmic reticulum stress

    Science.gov (United States)

    Hata, Masayuki; Ikeda, Hanako O.; Kikkawa, Chinami; Iwai, Sachiko; Muraoka, Yuki; Hasegawa, Tomoko; Kakizuka, Akira; Yoshimura, Nagahisa

    2017-01-01

    Ischemic neural damages cause several devastating diseases, including brain stroke and ischemic retinopathies, and endoplasmic reticulum (ER) stress has been proposed to be the underlying mechanism of the neuronal cell death of these conditions. We previously synthesized Kyoto University substances (KUSs) as modulators of valosin-containing protein (VCP); KUSs inhibit VCP ATPase activity and protect cells from different cell death-inducing insults. Here, we examined the efficacy of KUS121 in a rat model of retinal ischemic injury. Systemic administration of KUS121 to rats with ischemic retinal injury significantly suppressed inner retinal thinning and death of retinal ganglion and amacrine cells, with a significant functional maintenance of visual functions, as judged by electroretinography. Furthermore, intravitreal injection of KUS121, which is the clinically preferred route of drug administration for retinal diseases, appeared to show an equal or better neuroprotective efficacy in the ischemic retina compared with systemic administration. Indeed, induction of the ER stress marker C/EBP homologous protein (CHOP) after the ischemic insult was significantly suppressed by KUS121 administration. Our study suggests VCP modulation by KUS as a promising novel therapeutic strategy for ischemic neuronal diseases. PMID:28317920

  19. An Optimized Culture Method of Rat Dorsal Root Ganglion Neurons

    Institute of Scientific and Technical Information of China (English)

    LIUYin; CHENJing-Hong; GONGZe-Hui

    2004-01-01

    AIM: To establish a primary culture technique of acutely isolated dorsal root ganglion (DRG) neurons, and provide a simple & useful in vitro model for study of analgesia. Methods: Acutely isolated dorsal root ganglion (DRG) neurons were planted and cultured; the configuration and growth characters of DRG neurons were observed through inverted microscope.

  20. Retinal prosthesis that incorporates the organization of the nerve fibre layer.

    Science.gov (United States)

    FitzGibbon, Thomas

    2017-01-30

    Recent efforts to restore partial vision in blind patients have made significant progress. Currently, prosthetic design concentrates on stimulating as many foveal retinal ganglion cells as possible but is hampered by stimulation of the nerve fibre layer. This results in a nonvisuotopic arrangement of phosphenes (stimulation percepts). This article suggests that by extending the stimulation area well beyond the fovea and stimulating the nerve fibre layer, axons from any remaining ganglion cells in more peripheral regions of the retina (low acuity) can be used to generate a visuotopic map. Stimulation of the fibre layer will generate a large number of stimulation percepts; however, it is unlikely that these will have sufficient topographic order to be immediately useful to the patient. Thus, it will be necessary to recreate an ordered visuotopic map by using appropriate computer algorithms and interactions between the patient and the clinician.

  1. Retinal flow cytometer

    OpenAIRE

    Alt, C.; Veilleux, I.; H. Lee; Pitsillides, C. M.; Côté, D.; Lin, C.P.

    2007-01-01

    The in vivo flow cytometer is an instrument capable of continuous, real-time monitoring of fluorescently labeled cells in the circulation without the need to draw blood samples. However, the original system probes a single vessel in the mouse ear; the small sample volume limits the sensitivity of the technique. We describe an in vivo retinal flow cytometer that simultaneously probes five artery–vein pairs in the mouse eye by circularly scanning a small laser spot rapidly around the optic nerv...

  2. Inherited Retinal Degenerative Disease Registry

    Science.gov (United States)

    2016-03-21

    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

  3. Idebenone protects against retinal damage and loss of vision in a mouse model of Leber's hereditary optic neuropathy.

    Directory of Open Access Journals (Sweden)

    Fabrice D Heitz

    Full Text Available Leber's hereditary optic neuropathy (LHON is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients.

  4. Idebenone protects against retinal damage and loss of vision in a mouse model of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Heitz, Fabrice D; Erb, Michael; Anklin, Corinne; Robay, Dimitri; Pernet, Vincent; Gueven, Nuri

    2012-01-01

    Leber's hereditary optic neuropathy (LHON) is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC) dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients.

  5. Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis.

    Directory of Open Access Journals (Sweden)

    Cheryl A Arcinue

    Full Text Available To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula compared with age-matched HIV-negative controls.Cohort of patients with known HIV under CART (combination Antiretroviral Therapy treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT to assess retinal layers and retinal thickness.Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior, the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2. A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea. We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer was also significantly thickened in all the different locations scanned compared with HIV-negative controls.Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

  6. Imaging of long-term retinal damage after resolved cotton wool spots

    Science.gov (United States)

    Gomez, Maria Laura; Mojana, Francesca; Bartsch, Dirk-Uwe; Freeman, William R.

    2014-01-01

    Purpose Human Immunodeficiency Virus (HIV) patients develop non-infectious retinopathy characterized by retinal cotton wool spots (CWS) and micro vascular abnormalities. Ophthalmoscopically CWS fade with time. We hypothesized that structural changes should be permanent and possibly visible well after ophthalmoscopic resolution. We used simultaneous spectral domain optical coherence tomography/ scanning laser ophthalmoscope (SD-OCT/SLO) to allow co-localization of the lesions and determine the extent and location of residual damage after ophthalmoscopic resolution of the lesions. Design Retrospective, non-interventional case series. Participants Eight eyes of seven human immunodeficiency virus (HIV) patients with nineteen resolved retinal cotton wool spots. Methods Nineteen retinal cotton wool spots were imaged between 2 and 16 (median 7.84) years after the acute lesions using simultaneous SD-OCT and scanning laser ophthalmoscope (SLO) examinations. The areas of the previous CWS were scanned by overlaying the color retinal image over the SLO image and scanning at high resolution in the horizontal plane thru the resolved lesion. Each CWS lesion had a control area taken from the same eye within 2 disc diameters of the lesion. The thickness of each of the retinal layers was compared between lesions and control areas using a paired t-test using multi-test correction. Main Outcome Measures Thickness of the retinal nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear (ONL) layers. Results The largest loss of thickness was seen in the retinal GCL with a 43% reduction in thickness. There was a statistically significant thinning of the retinal NFL, GCL, IPL, INL and OPL. The median thickness differences ranged from 5 to 7 microns. This difference was highly statistically significant. Another striking finding was the displacement of the ONL towards the retinal surface

  7. Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease

    Directory of Open Access Journals (Sweden)

    Carolina P. B. Gracitelli

    2016-01-01

    Full Text Available Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life.

  8. Sensitivity of Retinal Ganglion Cell Photoreceptors in Traumatic Brain Injury Patients with Photophobia

    Science.gov (United States)

    2015-11-01

    AEVR-sponsored Congressional Briefing on deployment-related vision trauma research on Capitol Hill, Washington DC. Presented seminar entitled...Changes from Head Trauma ”. The paper, entitled “Blue and red light-evoked pupil responses in photophobic subjects with TBI” required minor revisions...fluctuation (constriction and dilation) was quantified with fast Fourier transforms. Hartwick; W81XWH-12-1-0434 6 Cases Controls p-value

  9. [Application of retinal oximeter in ophthalmology].

    Science.gov (United States)

    Li, Jing; Ma, Jianmin; Wang, Ningli

    2015-11-01

    Retinal oximeter is a new machine which has been used in the diagnose, treatment and research of several ophthalmic diseases for recent years. It allows ophthalmologists to gain retinal oxygen saturation directly. Therefore, retinal oximeter might be useful for ophthalmologists to understand ophthalmic diseases more deeper and clarify the impact of ischemia on retinal function. It has been reported in the literatures that retinal oximeter has potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, central retinal vein and artery occlusion, retinitis pigmentosa, glaucomatous optic neuropathy, et al. In this thesis, the application of retinal oximeter in ophthalmology is reviewed.

  10. Profile and Determinants of Retinal Optical Intensity in Normal Eyes with Spectral Domain Optical Coherence Tomography.

    Directory of Open Access Journals (Sweden)

    Binyao Chen

    Full Text Available To investigate the profile and determinants of retinal optical intensity in normal subjects using 3D spectral domain optical coherence tomography (SD OCT.A total of 231 eyes from 231 healthy subjects ranging in age from 18 to 80 years were included and underwent a 3D OCT scan. Forty-four eyes were randomly chosen to be scanned by two operators for reproducibility analysis. Distribution of optical intensity of each layer and regions specified by the Early Treatment of Diabetic Retinopathy Study (ETDRS were investigated by analyzing the OCT raw data with our automatic graph-based algorithm. Univariate and multivariate analyses were performed between retinal optical intensity and sex, age, height, weight, spherical equivalent (SE, axial length, image quality, disc area and rim/disc area ratio (R/D area ratio.For optical intensity measurements, the intraclass correlation coefficient of each layer ranged from 0.815 to 0.941, indicating good reproducibility. Optical intensity was lowest in the central area of retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer and photoreceptor layer, except for the retinal pigment epithelium (RPE. Optical intensity was positively correlated with image quality in all retinal layers (0.5530.05. There was no relationship between retinal optical intensity and sex, height, weight, SE, axial length, disc area and R/D area ratio.There was a specific pattern of distribution of retinal optical intensity in different regions. The optical intensity was affected by image quality and age. Image quality can be used as a reference for normalization. The effect of age needs to be taken into consideration when using OCT for diagnosis.

  11. Retinal Morphology and Sensitivity Are Primarily Impaired in Eyes with Neuromyelitis Optica Spectrum Disorder (NMOSD)

    Science.gov (United States)

    Akiba, Ryutaro; Yokouchi, Hirotaka; Mori, Masahiro; Oshitari, Toshiyuki; Baba, Takayuki; Sawai, Setsu; Kuwabara, Satoshi; Yamamoto, Shuichi

    2016-01-01

    Background Previous studies of neuromyelitis optica spectrum disorder (NMOSD) using spectral domain optical coherence tomography (SD-OCT) showed that the outer nuclear layer (ONL) in eyes without a history of optic neuritis (ON) was thinner than that of healthy controls. It remains unclear whether the ONL thinning is caused by a direct attack on the retina by an autoantibody or a retrograde degeneration. Objective To determine the mechanisms involved in the retinal damage in eyes with NMOSD without ON. Methods SD-OCT was used to determine the thicknesses of the different retinal layers of 21 eyes of 12 NMOSD patients without prior ON and 19 eyes of 10 healthy controls. Eyes with peripapillary retinal nerve fiber layer (RNFL) thinning were excluded to eliminate the confounding effects of retrograde degeneration. Microperimetry was used to determine the central retinal sensitivity. The data of the two groups were compared using generalized estimated equation models to account for inter-eye dependencies. Results The ganglion cell plus inner plexiform layer and the inner nuclear layer plus outer plexiform layer thicknesses of the NMOSD eyes were not significantly different from that of the control eyes (P = 0.28, P = 0.78). However, the ONL and average macular thickness (AMT) in the NMOSD eyes were significantly thinner than that of the control eyes (P = 0.022, P = 0.036). The retinal sensitivity in the central 10°, 10° to 2°, and 2° sectors were significantly lower in the NMOSD eyes than in the control eyes (P = 0.013, P = 0.022, P = 0.002). Conclusions The ONL thinning, AMT thinning, and reduced retinal sensitivity in eyes with NMOSD without significant peripapillary RNFL thinning are most likely due to direct retinal pathology. PMID:27936154

  12. Cat Scratch Disease (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Cat Scratch Disease KidsHealth > For Parents > Cat Scratch Disease A A A What's in this ... Doctor en español Enfermedad por arañazo de gato Cat scratch disease is a bacterial infection that a ...

  13. 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...... (MAP) minus the intraocular pressure (IOP). It was clamped to 0-30 mm Hg by continuous monitoring of MAP and adjustment of the IOP, which was controlled by cannulation of the anterior chamber. Inner retinal function was assessed by induced multifocal electroretinography (mfERG) with comparisons...... 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...

  14. A tortoiseshell male cat

    DEFF Research Database (Denmark)

    Pedersen, A. S.; Berg, Lise Charlotte; Almstrup, Kristian

    2014-01-01

    . Immunostaining using anti-vimentin and anti-VASA (DDX4) showed that only Sertoli cells and no germ cells were observed in the testicular tubules. As no sign of spermatogenesis was detected, we conclude that this is a classic case of a sterile, male tortoiseshell cat with a 39,XXY chromosome complement. © 2013 S...

  15. Vibrational Schroedinger Cats

    Science.gov (United States)

    Kis, Z.; Janszky, J.; Vinogradov, An. V.; Kobayashi, T.

    1996-01-01

    The optical Schroedinger cat states are simple realizations of quantum states having nonclassical features. It is shown that vibrational analogues of such states can be realized in an experiment of double pulse excitation of vibrionic transitions. To track the evolution of the vibrational wave packet we derive a non-unitary time evolution operator so that calculations are made in a quasi Heisenberg picture.

  16. The Fishing Cat

    Institute of Scientific and Technical Information of China (English)

    孙雅飞; 乐伟国

    2008-01-01

    @@ 一、故事内容 A cat goes fishing every day. He wants to eat fish, but he can't catch any fish. One day, he goes to the river as usual. Suddenly, a fish comes out. He catches the fish and putsthe fish in the basket. He's very happy, but he forgest to put the lid on the basket.

  17. 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

  18. 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

  19. Health and Behavioral Survey of over 8000 Finnish Cats

    Science.gov (United States)

    Vapalahti, Katariina; Virtala, Anna-Maija; Joensuu, Tara A.; Tiira, Katriina; Tähtinen, Jaana; Lohi, Hannes

    2016-01-01

    A comprehensive feline health survey was conducted to reveal breed-specific inheritable diseases in Finnish pedigree cats for genetic research. Prevalence of 19 disease categories and 227 feline diseases were defined in a study population of 8175 cats belonging to 30 breeds. Dental and oral diseases, with a prevalence of 28%, and dental calculus and gingivitis (21 and 8%, respectively) were the most prevalent disease category and diseases among all cats and in most of the breeds. An exception was Korats, which were more often affected by the diseases of the respiratory tract (23%) and asthma (19%). Other prevalent disease categories affected various organ systems, such as the skin (12%), the urinary system (12%), the digestive tract (11%), eyes (10%), the musculoskeletal system (10%), and genitals of female cats (17%). Prevalent health or developmental issues included repetitive vomiting (4%), tail kink (4%), feline odontoclastic resorption lesion (4%), urinary tract infections (4%), as well as cesarean section (6%) and stillborn kittens (6%) among female cats. We found 57 breed-specific conditions by Fisher’s exact tests and logistic regression analyses, including 32 previously described and 19 new breed-specific diseases. The genetic defect has already been found in six of them: polycystic kidney disease, progressive retinal atrophy, hypertrophic cardiomyopathy, and three types of tail malformations. Behavioral profiling revealed breed-specific traits, such as an increased human avoidance in British Short and Longhairs and a higher level of aggression in Turkish vans. Our epidemiological study reveals the overall health profile in Finnish pure and mixed breed cats and identifies many breed-specific conditions without molecular identity for genetic research. PMID:27622188

  20. Health and Behavioral Survey of over 8000 Finnish Cats.

    Science.gov (United States)

    Vapalahti, Katariina; Virtala, Anna-Maija; Joensuu, Tara A; Tiira, Katriina; Tähtinen, Jaana; Lohi, Hannes

    2016-01-01

    A comprehensive feline health survey was conducted to reveal breed-specific inheritable diseases in Finnish pedigree cats for genetic research. Prevalence of 19 disease categories and 227 feline diseases were defined in a study population of 8175 cats belonging to 30 breeds. Dental and oral diseases, with a prevalence of 28%, and dental calculus and gingivitis (21 and 8%, respectively) were the most prevalent disease category and diseases among all cats and in most of the breeds. An exception was Korats, which were more often affected by the diseases of the respiratory tract (23%) and asthma (19%). Other prevalent disease categories affected various organ systems, such as the skin (12%), the urinary system (12%), the digestive tract (11%), eyes (10%), the musculoskeletal system (10%), and genitals of female cats (17%). Prevalent health or developmental issues included repetitive vomiting (4%), tail kink (4%), feline odontoclastic resorption lesion (4%), urinary tract infections (4%), as well as cesarean section (6%) and stillborn kittens (6%) among female cats. We found 57 breed-specific conditions by Fisher's exact tests and logistic regression analyses, including 32 previously described and 19 new breed-specific diseases. The genetic defect has already been found in six of them: polycystic kidney disease, progressive retinal atrophy, hypertrophic cardiomyopathy, and three types of tail malformations. Behavioral profiling revealed breed-specific traits, such as an increased human avoidance in British Short and Longhairs and a higher level of aggression in Turkish vans. Our epidemiological study reveals the overall health profile in Finnish pure and mixed breed cats and identifies many breed-specific conditions without molecular identity for genetic research.

  1. Health and behavioral survey of over 8000 Finnish cats

    Directory of Open Access Journals (Sweden)

    Katariina Vapalahti

    2016-08-01

    Full Text Available A comprehensive feline health survey was conducted to reveal breed-specific inheritable diseases in Finnish pedigree cats for genetic research. Prevalences of 19 disease categories and 227 feline diseases were defined in a study population of 8175 cats belonging to 30 breeds. Dental and oral diseases with a prevalence of 28% and dental calculus and gingivitis (21% and 8%, respectively were the most prevalent disease category and diseases among all cats and in most of the breeds. An exception was Korats, which were more often affected by the diseases of the respiratory tract (23% and asthma (19%. Other prevalent disease categories affected various organ systems such as the skin (12%, the urinary system (12%, the digestive tract (11%, eyes, (10%, the musculoskeletal system (10%, and genitals of female cats (17%. Prevalent health or developmental issues included repetitive vomiting (4%, tail kink (4%, feline odontoclastic resorption lesion (FORL (4%, urinary tract infections (4%, as well as caesarean section (6% and stillborn kittens (6% among female cats. We found 57 breed-specific conditions by Fisher’s exact tests and logistic regression analyses, including 32 previously described and 19 new breed-specific diseases. The genetic defect has already been found in six of them: polycystic kidney disease (PKD, progressive retinal atrophy (PRA, hypertrophic cardiomyopathy (HCM and three types of tail malformations. Behavioral profiling revealed breed-specific traits, such as an increased human avoidance in British Short and Longhairs and a higher level of aggression in Turkish vans. Our epidemiological study reveals the overall health profile in Finnish pure and mixed breed cats and identifies many breed-specific conditions without molecular identity for genetic research.

  2. Neuroretinitis with Branch Retinal Artery Occlusion in a 15-Year-Old Female

    Directory of Open Access Journals (Sweden)

    Sina Ahmadi

    2013-11-01

    Full Text Available We report a case of Bartonella henselae neuroretinitis with significant disc and peripapillary edema, branch retinal artery occlusion without macula involvement and well preserved central vision. A 15-year-old female presented with loss of vision over 4 weeks in the left eye. She had a history of cat exposure, but a cat scratch, insect bite or conjunctivitis was not reported. An inferotemporal arcuate scotoma developed during the acute phase and persisted over the course of the follow-up.

  3. Retinal detachment surgery without cryotherapy.

    OpenAIRE

    Chignell, A H; Markham, R H

    1981-01-01

    A series of cases of retinal detachment treated without the application of cryotherapy at the time of surgery has been studied. The omission of cryotherapy while not interfering with retinal reattachment, carries the risk of redetachment at a later date. Macular pucker may still occur in spite of the absence of cryotherapy.

  4. Genetic testing in domestic cats.

    Science.gov (United States)

    Lyons, Leslie A

    2012-12-01

    Varieties of genetic tests are currently available for the domestic cat that support veterinary health care, breed management, species identification, and forensic investigations. Approximately thirty-five genes contain over fifty mutations that cause feline health problems or alterations in the cat's appearance. Specific genes, such as sweet and drug receptors, have been knocked-out of Felidae during evolution and can be used along with mtDNA markers for species identification. Both STR and SNP panels differentiate cat race, breed, and individual identity, as well as gender-specific markers to determine sex of an individual. Cat genetic tests are common offerings for commercial laboratories, allowing both the veterinary clinician and the private owner to obtain DNA test results. This article will review the genetic tests for the domestic cat, and their various applications in different fields of science. Highlighted are genetic tests specific to the individual cat, which are a part of the cat's genome.

  5. Ganglion cyst associated with triangular fibrocartilage complex tear that caused ulnar nerve compression.

    Science.gov (United States)

    Bingol, Ugur Anil; Cinar, Can; Tasdelen, Neslihan

    2015-03-01

    Ganglions are the most frequently seen soft-tissue tumors in the hand. Nerve compression due to ganglion cysts at the wrist is rare. We report 2 ganglion cysts arising from triangular fibrocartilage complex, one of which caused ulnar nerve compression proximal to the Guyon's canal, leading to ulnar neuropathy. Ganglion cysts seem unimportant, and many surgeons refrain from performing a general hand examination.

  6. Multiple Retinal Axons Converge onto Relay Cells in the Adult Mouse Thalamus

    Directory of Open Access Journals (Sweden)

    Sarah Hammer

    2015-09-01

    Full Text Available Activity-dependent refinement of neural circuits is a fundamental principle of neural development. This process has been well studied at retinogeniculate synapses—synapses that form between retinal ganglion cells (RGCs and relay cells within the dorsal lateral geniculate nucleus. Physiological studies suggest that shortly after birth, inputs from ∼20 RGCs converge onto relay cells. Subsequently, all but just one to two of these inputs are eliminated. Despite widespread acceptance, this notion is at odds with ultrastructural studies showing numerous retinal terminals clustering onto relay cell dendrites in the adult. Here, we explored this discrepancy using brainbow AAVs and serial block face scanning electron microscopy (SBFSEM. Results with both approaches demonstrate that terminals from numerous RGCs cluster onto relay cell dendrites, challenging the notion that only one to two RGCs innervate each relay cell. These findings force us to re-evaluate our understanding of subcortical visual circuitry.

  7. 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.

  8. Cat scratch disease.

    Science.gov (United States)

    Bozhkov, V; Madjov, R; Plachkov, I; Arnaudov, P; Chernopolsky, P; Krasnaliev, I

    2014-01-01

    Approximately 24,000 people are infected with cat scratch disease (CSD) every year. CSD is caused by the bacteria Bartonella henselae, a gram-negative bacteria most often transmitted to humans through a bite or scratch from an infected cat or kitten. Although CSD is often a benign and self-limiting condition, it can affect any major organ system in the body, manifesting in different ways and sometimes leading to lifelong sequelae. It is a disease that is often overlooked in primary care because of the wide range of symptom presentation and relative rarity of serious complications. It is important for health care providers to recognize patients at risk for CSD, know what laboratory testing and treatments are available, and be aware of complications that may arise from this disease in the future.

  9. The Cheshire Cat revisited

    CERN Document Server

    Vento, V

    1998-01-01

    The concept of effective field theory leads in a natural way to a construction principle for phenomenological sensible models known under the name of the Cheshire Cat Principle. We review its formulation in the chiral bag scenario and discuss its realization for the flavor singlet axial charge. Quantum effects inside the chiral bag induce a color anomaly which requires a compensating surface term to prevent breakdown of color gauge invariance. The presence of this surface term allows one to derive in a gauge-invariant way a chiral-bag version of the Shore-Veneziano two-component formula for the flavor-singlet axial charge of the proton. We show that one can obtain a striking Cheshire-Cat phenomenon with a negligibly small singlet axial charge.

  10. Sympathetic innervation of the carotid bifurcation in the rabbit and cat: blood vessels, carotid body and carotid sinus. A fluorescence and electron microscopic study.

    Science.gov (United States)

    Knoche, H; Kienecker, E W

    1977-10-21

    Two postganglionic branches of the superior cervical ganglion enter the area of the carotid bifurcation in the rabbit and the cat. The common and external carotid arteries receive a rich adrenergic nerve supply, which can be demonstrated by fluorophores of biogenic amines appearing after formaldehyde treatment. The internal carotid artery is only sparsely innervated; however, it shows a dense sympathetic supply at the site of pressor receptors. Following removal of the superior cervical ganglion, a total loss of fluorescent adrenergic nerves occurs and degeneration of nerve endings possessing dense core vesicles is conspicuous. These nerve terminals are situated mainly subendothelially in the carotid body sinusoids; they only rarely terminate on type I cells.

  11. Role of tumor necrosis factor-alpha in zebrafish retinal neurogenesis and myelination

    Science.gov (United States)

    Lei, Xu-Dan; Sun, Yan; Cai, Shi-Jiao; Fang, Yang-Wu; Cui, Jian-Lin; Li, Yu-Hao

    2016-01-01

    AIM To investigate the role of tumor necrosis factor-alpha (TNF-α) in zebrafish retinal development and myelination. METHODS Morpholino oligonucleotides (MO), which are complementary to the translation start site of the wild-type embryonic zebrafish TNF-α mRNA sequence, were synthesized and injected into one- to four-cell embryos. The translation blocking specificity was verified by Western blotting using an anti-TNF-α antibody, whole-mount in situ hybridization using a hepatocyte-specific mRNA probe ceruloplasmin (cp), and co-injection of TNF-α MO and TNF-α mRNA. An atonal homolog 7 (atoh7) mRNA probe was used to detect neurogenesis onset. The retinal neurodifferentiation was analyzed by immunohistochemistry using antibodies Zn12, Zpr1, and Zpr3 to label ganglion cells, cones, and rods, respectively. Myelin basic protein (mbp) was used as a marker to track and observe the myelination using whole-mount in situ hybridization. RESULTS Targeted knockdown of TNF-α resulted in specific suppression of TNF-α expression and a severely underdeveloped liver. The co-injection of TNF-α MO and mRNA rescued the liver development. Retinal neurogenesis in TNF-α morphants was initiated on time. The retina was fully laminated, while ganglion cells, cones, and rods were well differentiated at 72 hours post-fertilization (hpf). mbp was expressed in Schwann cells in the lateral line nerves and cranial nerves from 3 days post-fertilization (dpf) as well as in oligodendrocytes linearly along the hindbrain bundles and the spinal cord from 4 dpf, which closely resembled its endogenous profile. CONCLUSION TNF-α is not an essential regulator for retinal neurogenesis and optic myelination. PMID:27366683

  12. Retinal neurodegeneration in Wilson's disease revealed by spectral domain optical coherence tomography.

    Directory of Open Access Journals (Sweden)

    Philipp Albrecht

    Full Text Available BACKGROUND/OBJECTIVE: In addition to cirrhosis of the liver, Wilson's disease leads to copper accumulation and widespread degeneration of the nervous system. Delayed visual evoked potentials (VEPs suggest changes to the visual system and potential structural changes of the retina. METHODS: We used the latest generation of spectral domain optical coherence tomography to assess the retinal morphology of 42 patients with Wilson's disease and 76 age- and sex-matched controls. We measured peripapillary retinal nerve fiber layer (RNFL thickness and total macular thickness and manually segmented all retinal layers in foveal scans of 42 patients with Wilson's disease and 76 age- and sex-matched controls. The results were compared with VEPs and clinical parameters. RESULTS: The mean thickness of the RNFL, paramacular region, retinal ganglion cell/inner plexiform layer and inner nuclear layer was reduced in Wilson's disease. VEPs were altered with delayed N75 and P100 latencies, but the N140 latency and amplitude was unchanged. An analysis of the laboratory parameters indicated that the serum concentrations of copper and caeruloplasmin positively correlated with the thickness of the outer plexiform layer and with N75 and P100 VEP latencies. CONCLUSION: Neuronal degeneration in Wilson's disease involves the retina and changes can be quantified by optical coherence tomography. While the VEPs and the thickness of the outer plexiform layer appear to reflect the current copper metabolism, the thicknesses of the RNFL, ganglion cell/inner plexiform layer, inner nuclear layer and the total paramacular thickness may be the best indicators of chronic neuronal degeneration.

  13. The planar cell polarity protein Vangl2 is required for retinal axon guidance.

    Science.gov (United States)

    Leung, Vicki; Iliescu, Alexandra; Jolicoeur, Christine; Gravel, Michel; Apuzzo, Sergio; Torban, Elena; Cayouette, Michel; Gros, Philippe

    2016-02-01

    Vangl2 plays a critical role in the establishment of planar cell polarity (PCP). Previously, we detected expression of Vangl2 in the developing retina during late embryogenesis, which led us to investigate the possible role of Vangl2-mediated PCP signaling in eye development. We have generated a Vangl2(BGeo) knock-in mouse allowing us to evaluate Vangl2 mRNA expression during retinal development, and used an isoform-specific antibody to examine Vangl2 protein expression in cryosections. To investigate the role of Vangl2 in retinal development, we examined eyes taken from embryos homozygous for independent alleles of Looptail (Lp, Lp(m1jus) ) mutant mice. We found that Vangl2 mRNA and protein are dynamically expressed in the developing embryonic and postnatal retina, with Vangl2 expression becoming progressively restricted to the ganglion cell layer and optic nerve as the retina matures. The expression pattern of Vangl2 transcript and protein is most prominent in retinal ganglion cells (RGC), and their axons. Additionally, we show that Vangl2 is required for retinal and optic nerve development as Vangl2 (Lp/Lp) mutant embryos display a significantly reduced eye size, marked thickening of the retina, and striking abnormalities in the morphology of the optic nerve (significant hypoplasia, and aberrant exit trajectory). Notably, we identified a salient intraretinal axon guidance defect in Vangl2 (Lp/Lp) mutant embryos through which axon bundles traverse the entire thickness of the retina and become trapped within the subretinal space. Our observations identify a new and essential role for Vangl2-dependent PCP signaling in the intraretinal path-finding of RGC axons.

  14. Mineral metabolism in cats

    OpenAIRE

    Pineda Martos, Carmen María

    2014-01-01

    The present Doctoral Thesis wa metabolism in the feline species. Through a series of studies, the relationship between calcium metabolism and the main hormones involved in it has been determined metabolism during the juvenile stage of growing cats effects linked to feeding calculolytic diets on feline mineral metabolism. The first part of the work was aimed the quantification of intact (I-PTH) and whole PTH) and to characterize the dynamics of PTH secretion, including ...

  15. Acute retinal necrosis

    Directory of Open Access Journals (Sweden)

    Hugo Hernán Ocampo

    2009-12-01

    Full Text Available Purpose: Clinical features in a case of acute retinal necrosis are described as well as its diagnostic approach and response to early treatment. Methods: This is a descriptive and retrospective study case report of a 26 year old male patient who arrived to the emergency room with a three day history of sudden visual loss in the right eye (RE. At initial evaluation a visual acuity of hand movements in the RE, 20/15 in the left eye (LE and a right relative afferent pupillary defect were found. Fundoscopy revealed profuse soft exudates and hemorrhages involving posterior pole, inferior hemiretina and superotemporal periphery. Infectious workup and fluoresceinic angiography were made and positive serologies for herpes virus types 1 and 2, without HIV, were found. A diagnosis of acute retinal necrosis was made and treatment with intravenous valgancyclovir for two weeks and intra-vitreous triamcinolone for severe vasculitis, was given. Then a 3 months treatment with oral antiviral agents was prescribed. Results: Patient’s evolution showed improvement with treatment and at two and a half months of follow up, visual acuity was 20/50 in the right eye, normal slit lamp examination, tonometry of 12 mm Hg and fundoscopy improved when compared to initial pictures.Conclusions: A high index of suspicion is needed for diagnosing ARN taking into account clinical findings. Prompt intravenous and intra-vitreous treatments are needed to achieve good clinical and functional outcomes and to avoid central nervous system complications.

  16. Bimatoprost protects retinal neuronal damage via Akt pathway.

    Science.gov (United States)

    Takano, Norihito; Tsuruma, Kazuhiro; Ohno, Yuta; Shimazawa, Masamitsu; Hara, Hideaki

    2013-02-28

    Worldwide, prostaglandin analogs, such as bimatoprost, have become the major therapeutic class for medical treatment of glaucoma because of their efficacy and generally well tolerated systemic safety profile. However, the detailed mechanism of the direct action of bimatoprost on retinal ganglion cells (RGC) has rarely been understood. Thus, in this study, we elucidated the mechanism of the protective effects of bimatoprost on RGC against oxidative stress. To examine the protective effects of bimatoprost, cultured RGC with various concentrations of bimatoprost (in both free acid and amide form) were exposed to l-buthionin-(S,R)-sulfoximine (BSO) plus glutamate or serum depletion in vitro and intravitreal injection of N-methyl-D-aspartate (NMDA) was used to induce retinal damage in vivo. To elucidate the protective mechanism of bimatoprost, we used western blot analysis to investigate the phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Bimatoprost significantly reduced BSO plus glutamate- and serum deprivation-induced death in concentration-dependent manners. Bimatoprost induced activation of Akt and ERK, and a phosphatidylinositol 3-kinase inhibitor, LY294002, attenuated the protective effect of bimatoprost. On the other hand, a mitogen-activated protein kinase kinase inhibitor, U0126, exhibited protective effect unexpectedly. Moreover, ERK was more phosphorylated by attenuation of Akt activity in cultured RGC. In an in vivo study, bimatoprost reduced NMDA-induced RGC death. Taken together, these findings indicate that bimatoprost has protective effects on in vitro and in vivo retinal damage, suggesting that the mechanism underlying may be via the Akt pathway, which may modulate the ERK pathway.

  17. Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration

    Science.gov (United States)

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

    2016-01-01

    Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF) and nerve growth factor (NGF), suggest that they are good therapeutic candidates for neurodegenerative diseases. Glaucoma is a neurodegenerative disease of the eye that causes irreversible blindness. It is characterized by damage to the optic nerve, usually due to high intraocular pressure (IOP), and progressive degeneration of retinal neurons called retinal ganglion cells (RGCs). Current therapy for glaucoma focuses on reduction of IOP, but neuroprotection may also be beneficial. BDNF is a powerful neuroprotective agent especially for RGCs. Exogenous application of BDNF to the retina and increased BDNF expression in retinal neurons using viral vector systems are both effective in protecting RGCs from damage. Furthermore, induction of BDNF expression by agents such as valproic acid has also been beneficial in promoting RGC survival. In this review, we discuss the therapeutic potential of neurotrophic factors in retinal diseases and focus on the differential roles of glial and neuronal TrkB in neuroprotection. We also discuss the role of neurotrophic factors in neuroregeneration. PMID:27657046

  18. An Intraocular Camera for Retinal Prostheses: Restoring Sight to the Blind

    Science.gov (United States)

    Stiles, Noelle R. B.; McIntosh, Benjamin P.; Nasiatka, Patrick J.; Hauer, Michelle C.; Weiland, James D.; Humayun, Mark S.; Tanguay, Armand R., Jr.

    Implantation of an intraocular retinal prosthesis represents one possible approach to the restoration of sight in those with minimal light perception due to photoreceptor degenerating diseases such as retinitis pigmentosa and age-related macular degeneration. In such an intraocular retinal prosthesis, a microstimulator array attached to the retina is used to electrically stimulate still-viable retinal ganglion cells that transmit retinotopic image information to the visual cortex by means of the optic nerve, thereby creating an image percept. We describe herein an intraocular camera that is designed to be implanted in the crystalline lens sac and connected to the microstimulator array. Replacement of an extraocular (head-mounted) camera with the intraocular camera restores the natural coupling of head and eye motion associated with foveation, thereby enhancing visual acquisition, navigation, and mobility tasks. This research is in no small part inspired by the unique scientific style and research methodologies that many of us have learned from Prof. Richard K. Chang of Yale University, and is included herein as an example of the extent and breadth of his impact and legacy.

  19. Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice.

    Science.gov (United States)

    Hafler, Brian P; Klein, Zoe A; Jimmy Zhou, Z; Strittmatter, Stephen M

    2014-11-07

    Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn(-/-) mice develop degenerative pathology similar to features of human CLN11.

  20. Evaluation of micro Electroretinograms Recorded with Multiple Electrode Array to Assess Focal Retinal Function

    Science.gov (United States)

    Fujii, Momo; Sunagawa, Genshiro A.; Kondo, Mineo; Takahashi, Masayo; Mandai, Michiko

    2016-01-01

    Full-field electroretinograms (ERGs) are used to objectively assess the mass function of the retina, whereas focal ERGs are used to evaluate the focal retinal function. The purpose of this study was to determine the usefulness of a multiple electrode array (MEA) system for recording ex vivo micro ERGs (mERGs) together with multiunit spike responses of the retinal ganglion cells (RGCs) to assess focal retinal function in isolated mouse retinas. The a- and b-waves of the full-field ERGs were present in the mERG. The b-wave was blocked by L-AP4, an inhibitor of the mGluR6 receptor, and the OFF-component was blocked by exposure to PDA, an antagonist of ionotropic glutamate receptors, with a corresponding RGC responses. mERGs were also recorded from mice with progressive retinal degeneration, the C57BL/6J-Pde6brd1-2J/J (rd1) mice, from which conventional full-field ERGs are non-recordable. A blockade of the glutamate receptors indicated that the negative wave of rd1 mice do not originate from the photoreceptors but from the second or third order neurons. This technique of recording mERGs will be useful in assessing the focal properties of the retinas obtained from eyes with pathology and also to follow the recovery of the physiology of the retina in regenerative studies. PMID:27480484

  1. Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.

    Directory of Open Access Journals (Sweden)

    Jing Xia

    Full Text Available During retina development, retinal progenitor cell (RPC proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic and protective functions for neural tissue-derived cells. Here, we show that the expanded RPC cultures treated with BMSC-derived conditioned medium (CM which was substantially enriched for bFGF and CNTF, expressed clearly increased levels of nuclear receptor TLX, an essential regulator of neural stem cell (NSC self-renewal, as well as betacellulin (BTC, an EGF-like protein described as supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF markedly favoured RPC differentiation towards retinal neurons, including Brn3a-positive retinal ganglion cells (RGCs and rhodopsin-positive photoreceptors, and clearly diminished retinal glial cell differentiation. These findings demonstrate that BMSCs supported RPC proliferation and neuronal differentiation which may be partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of RPC culture systems, and suggest a means for optimizing RPC cell fate determination in vitro.

  2. Physiological variation of retinal layer thickness is not caused by hydration: a randomised trial.

    Science.gov (United States)

    Balk, Lisanne J; Oberwahrenbrock, Timm; Uitdehaag, Bernard M J; Petzold, Axel

    2014-09-15

    There is evidence for physiological variation of retinal thicknesses as determined by optical coherence tomography (OCT). We tested if such changes could be explained by hydration and would exceed what may be expected from normal ageing. Subjects (n=26) of a previous study were re-assessed and were randomised to 3 groups of a hydration escalation trial (no hydration, 1× hydration, 2× hydration). Automated retinal layer segmentations were performed for the macular retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL). The averaged volumes were calculated for the central foveola, 3 mm and 6 mm circles of the ETDRS grid. Following oral hydration there were no significant differences of retinal layer thicknesses between the three randomised groups in any of the ETDRS regions at any time-point. Ageing related changes were significant over an 18 month period for the GCL. The negative outcome of this trial implies that, until the causes for the observed variation are resolved, investigators may need to accept, and include into trial power calculations, a small degree of variation (<1%) of quantitative SD-OCT imaging either due to human physiology or instrument/software related factors.

  3. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

    Science.gov (United States)

    Sohn, Elliott H; van Dijk, Hille W; Jiao, Chunhua; Kok, Pauline H B; Jeong, Woojin; Demirkaya, Nazli; Garmager, Allison; Wit, Ferdinand; Kucukevcilioglu, Murat; van Velthoven, Mirjam E J; DeVries, J Hans; Mullins, Robert F; Kuehn, Markus H; Schlingemann, Reinier Otto; Sonka, Milan; Verbraak, Frank D; Abràmoff, Michael David

    2016-05-10

    Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

  4. Simultaneous segmentation of retinal surfaces and microcystic macular edema in SDOCT volumes

    Science.gov (United States)

    Antony, Bhavna J.; Lang, Andrew; Swingle, Emily K.; Al-Louzi, Omar; Carass, Aaron; Solomon, Sharon; Calabresi, Peter A.; Saidha, Shiv; Prince, Jerry L.

    2016-03-01

    Optical coherence tomography (OCT) is a noninvasive imaging modality that has begun to find widespread use in retinal imaging for the detection of a variety of ocular diseases. In addition to structural changes in the form of altered retinal layer thicknesses, pathological conditions may also cause the formation of edema within the retina. In multiple sclerosis, for instance, the nerve fiber and ganglion cell layers are known to thin. Additionally, the formation of pseudocysts called microcystic macular edema (MME) have also been observed in the eyes of about 5% of MS patients, and its presence has been shown to be correlated with disease severity. Previously, we proposed separate algorithms for the segmentation of retinal layers and MME, but since MME mainly occurs within specific regions of the retina, a simultaneous approach is advantageous. In this work, we propose an automated globally optimal graph-theoretic approach that simultaneously segments the retinal layers and the MME in volumetric OCT scans. SD-OCT scans from one eye of 12 MS patients with known MME and 8 healthy controls were acquired and the pseudocysts manually traced. The overall precision and recall of the pseudocyst detection was found to be 86.0% and 79.5%, respectively.

  5. Treatment of Laser-Induced Retinal Injuries

    Science.gov (United States)

    1989-06-29

    Distribution List (enclosed) bI’TF rruIoN STATEMEN A Approved for publi reljaso Disatbunon Unlimited TREATMENT OF LASER-INDUCED RETINAL INJURIES FINAL...suprathreshold retinal laser lesions II. Subthreshold retinal laser lesions III. Effect of steroid treatment on laser-induced retinal injury Discussion and...In the present study we investigated the effect of corticosteroid treatment of argon laser-induced retinal injury on vitreal accumulation of both

  6. Antibodies against Pax6 immunostain amacrine and ganglion cells and neuronal progenitors, but not rod precursors, in the normal and regenerating retina of the goldfish.

    Science.gov (United States)

    Hitchcock, P F; Macdonald, R E; VanDeRyt, J T; Wilson, S W

    1996-03-01

    Pax6 is a developmental regulatory gene that plays a key role in the development of the embryonic brain, eye, and retina. This gene is also expressed in discrete groups of neurons within the adult brain. In this study, antibodies raised against a fusion protein from a zebra fish pax6 cDNA were used to investigate the expression of the pax6 gene in the mature, growing, and regenerating retina of the goldfish. On western blots of retinal proteins, the pax6 antibodies recognize a single band at the approximate size of the zebra fish pax6 protein. In retinal sections, the antibodies label the nuclei of mature amacrine and some ganglion cells. At the retinal margin, where neurogenesis and cellular differentiation continually occur in goldfish, the antibodies label neuronal progenitors and the newly postmitotic neurons. Following injury and during neuronal regeneration, the antibodies label mitotically active progenitors of regenerating neurons. Rod precursors, proliferating cells that normally give rise solely to rod photoreceptors and are the presumed antecedents of the injury-stimulated neuronal progenitors, are not immunostained by antibodies to the pax6 protein. The results of this study document the identity of pax6-expressing cells in the mature retina and demonstrate that in the goldfish pax6 is expressed in neuronal progenitors during both retinal growth and regeneration.

  7. Chemical stimulation of rat retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis

    Science.gov (United States)

    Inayat, Samsoon; Rountree, Corey M.; Troy, John B.; Saggere, Laxman

    2015-02-01

    Objective. No cure currently exists for photoreceptor degenerative diseases, which cause partial or total blindness in millions of people worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter glutamate has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters. Approach. We injected controlled amounts of glutamate into rat retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz. Main results. We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous glutamate acts on RGC synapses similar to endogenous glutamate and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of glutamate stimulation was ˜ 290 μm from the injection site, comparable to current electrical prostheses. Further, the glutamate injections produced spatially differential responses in OFF, ON, and ON-OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision. Significance. We provide strong support for the feasibility of an epiretinal neurotransmitter

  8. Ultrastructure of the ganglion on human internal laryngeal nerve.

    Science.gov (United States)

    Ramaswamy, S; Shankar, S K; Manjunath, K Y; Devanathan, P H; Nityaseelan, N

    1994-01-01

    There is now definite evidence for the presence of a macroscopic ganglion on the human internal laryngeal nerve, with the distribution of its post-ganglionic fibres to the glands in the saccule and to the glands at the root of epiglottis in the vicinity of the opening of the saccule. This ganglion could be identified as early as 14 weeks in human foetal larynx, which contains immature neurons. Seven ganglia, dissected from human laryngectomy specimens and resected for carcinoma larynx, were studied by electron microscopy. Ultrastructurally, the neurons and the synaptic terminals had both small, round, luscent vesicles and dense core vesicles. Symmetrical, asymmetrical and electrical synaptic complexes were noted. A few neurons revealed degenerative changes suggestive of axotomy. The location of the ganglion on the internal laryngeal nerve, a branch of nervus vagus, and ultrastructural demonstration of large and small dense core vesicles and small luscent vesicles in the neurons of this ganglion, lead us to believe that the ganglion is parasympathetic in nature.

  9. Retinal Microvascular Abnormalities in Neurofibromatosis Type 1 Associated with Congenital Retinal Macrovessels

    Science.gov (United States)

    Makino, Shinji; Endoh, Katsuhisa; Tampo, Hironobu

    2013-01-01

    Here, we report a case of retinal microvascular abnormalities in a patient with neurofibromatosis type 1 (NF1) associated with congenital retinal macrovessels. An abnormal retinal macrovessel, crossing the macula horizontally, was detected in the right eye. Additionally, retinal microvascular abnormalities were detected. Eight years after the initial visit, the retinal microvascular abnormalities were noted to have changed substantially. We speculate that retinal microvascular abnormalities in NF1 may change dynamically over the years. PMID:23781366

  10. Retinal Microvascular Abnormalities in Neurofibromatosis Type 1 Associated with Congenital Retinal Macrovessels

    Directory of Open Access Journals (Sweden)

    Shinji Makino

    2013-01-01

    Full Text Available Here, we report a case of retinal microvascular abnormalities in a patient with neurofibromatosis type 1 (NF1 associated with congenital retinal macrovessels. An abnormal retinal macrovessel, crossing the macula horizontally, was detected in the right eye. Additionally, retinal microvascular abnormalities were detected. Eight years after the initial visit, the retinal microvascular abnormalities were noted to have changed substantially. We speculate that retinal microvascular abnormalities in NF1 may change dynamically over the years.

  11. A review of over three decades of research on cat-human and human-cat interactions and relationships.

    Science.gov (United States)

    Turner, Dennis C

    2017-01-22

    This review article covers research conducted over the last three decades on cat-human and human-cat interactions and relationships, especially from an ethological point of view. It includes findings on cat-cat and cat-human communication, cat personalities and cat-owner personalities, the effects of cats on humans, and problems caused by cats.

  12. Prevalence and Distribution of Segmentation Errors in Macular Ganglion Cell Analysis of Healthy Eyes Using Cirrus HD-OCT.

    Directory of Open Access Journals (Sweden)

    Rayan A Alshareef

    Full Text Available To determine the frequency of different types of spectral domain optical coherence tomography (SD-OCT scan artifacts and errors in ganglion cell algorithm (GCA in healthy eyes.Infrared image, color-coded map and each of the 128 horizontal b-scans acquired in the macular ganglion cell-inner plexiform layer scans using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA macular cube 512 × 128 protocol in 30 healthy normal eyes were evaluated. The frequency and pattern of each artifact was determined. Deviation of the segmentation line was classified into mild (less than 10 microns, moderate (10-50 microns and severe (more than 50 microns. Each deviation, if present, was noted as upward or downward deviation. Each artifact was further described as per location on the scan and zones in the total scan area.A total of 1029 (26.8% out of total 3840 scans had scan errors. The most common scan error was segmentation error (100%, followed by degraded images (6.70%, blink artifacts (0.09% and out of register artifacts (3.3%. Misidentification of the inner retinal layers was most frequent (62%. Upward Deviation of the segmentation line (47.91% and severe deviation (40.3% were more often noted. Artifacts were mostly located in the central scan area (16.8%. The average number of scans with artifacts per eye was 34.3% and was not related to signal strength on Spearman correlation (p = 0.36.This study reveals that image artifacts and scan errors in SD-OCT GCA analysis are common and frequently involve segmentation errors. These errors may affect inner retinal thickness measurements in a clinically significant manner. Careful review of scans for artifacts is important when using this feature of SD-OCT device.

  13. [Retinal vasculitis in lupic disease].

    Science.gov (United States)

    Brissaud, P; Laroche, L; Krulik, M; Prier, A M; Saraux, H; Canuel, C; Debray, J

    1985-01-01

    Three cases of retinal vasculitis in SLE-type diseases are reported. The first was central retinal vein occlusion occurring during clinical remission of SLE in a 55 year old black female. Prednisone maintenance therapy was unchanged and visual loss rapidly regressed with heparin therapy. The second case was a 33 year old black female in whom SLE was discovered following relapsing bilateral optic neuritis. A progressive visual improvement was obtained with high dose of prednisone (1 mg/kg/day). The third cas was a 17 year old white girl with retinal vasculitis. She had an unclassified connective tissue disease inaugurated by optic neuritis at the age of 10. High dose prednisone (1 mg/kg/day) was effective on the visual loss. Retinal vasculitis lesions in SLE and their therapy are reviewed.

  14. AUTOMATIC RETINAL VESSEL TORTUOSITY MEASUREMENT

    Directory of Open Access Journals (Sweden)

    Nidhal Khdhair El Abbadi

    2013-01-01

    Full Text Available Retinal vascular vessels have the role to indicate the retinal diseases and for systematic diseases when there are any abnormalities in retinal vascular pattern. A characteristic of the vascular pattern that is appreciated by clinicians is vascular tortuosity, i.e., how curved or kinked a blood vessel, either vein or artery, appears along its course. In this study we suggest a novel mask filter to track the blood vessel along its course and measuring the blood vessels tortuosity over the entire human retinal vessel network in fundus eye image, by using the arc to chord ratio. The suggested algorithm tested with straight and curve hand drawing lines and gives high accurate results.

  15. High-mobility group Box-1 is involved in NMDA-induced retinal injury the in rat retina.

    Science.gov (United States)

    Sakamoto, Kenji; Mizuta, Aya; Fujimura, Kyosuke; Kurauchi, Yuki; Mori, Asami; Nakahara, Tsutomu; Ishii, Kunio

    2015-08-01

    High-mobility group Box-1 (HMGB1) is known to be released from injured cells and to induce an inflammatory response. Although HMGB1 was reported to mediate ischemia-reperfusion injury of the brain, its role in glutamate excitotoxicity of the retina remains controversial. Here, the authors demonstrated the evidence that HMGB1 is involved in the retinal damage induced by NMDA. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal injection of NMDA (200 nmol/eye) or HMGB1 protein derived from bovines (5-15 μg/eye). Intravitreal anti-HMGB1 IgY (5 μg/eye) was simultaneously administered with NMDA or HMGB1. Seven days later, animals were killed and 5-μm retinal sections through the optic nerve head were obtained. These specimens were subjected to morphometry. Intravitreal NMDA and HMGB1 protein evoked cell loss in the ganglion cell layer 7 days later. Intravitreal anti-HMGB1 IgY reduced these damages. Anti-HMGB1 IgY reduced the number of 8-hydroxy-deoxyguanosine (8-OHdG)-positive cells induced by intravitreal NMDA. Toll-like receptor 2/4 antagonist peptide, receptor for advanced glycation end-products (RAGE) antagonist peptide, and FPS-ZM1 significantly reduced the retinal damage induced by HMGB1 protein. The results in the present study suggest that HMGB1 is at least in part involved in NMDA-induced retinal injury, and probably induces cell death of retinal ganglion cells with increase of oxidative stress, via activation of toll-like receptor 2/4 and RAGE in the rat retina.

  16. Estrogen activation of microglia underlies the sexually dimorphic differences in Nf1 optic glioma-induced retinal pathology.

    Science.gov (United States)

    Toonen, Joseph A; Solga, Anne C; Ma, Yu; Gutmann, David H

    2017-01-01

    Children with neurofibromatosis type 1 (NF1) develop low-grade brain tumors throughout the optic pathway. Nearly 50% of children with optic pathway gliomas (OPGs) experience visual impairment, and few regain their vision after chemotherapy. Recent studies have revealed that girls with optic nerve gliomas are five times more likely to lose vision and require treatment than boys. To determine the mechanism underlying this sexually dimorphic difference in clinical outcome, we leveraged Nf1 optic glioma (Nf1-OPG) mice. We demonstrate that female Nf1-OPG mice exhibit greater retinal ganglion cell (RGC) loss and only females have retinal nerve fiber layer (RNFL) thinning, despite mice of both sexes harboring tumors of identical volumes and proliferation. Female gonadal sex hormones are responsible for this sexual dimorphism, as ovariectomy, but not castration, of Nf1-OPG mice normalizes RGC survival and RNFL thickness. In addition, female Nf1-OPG mice have threefold more microglia than their male counterparts, and minocycline inhibition of microglia corrects the retinal pathology. Moreover, pharmacologic inhibition of microglial estrogen receptor-β (ERβ) function corrects the retinal abnormalities in female Nf1-OPG mice. Collectively, these studies establish that female gonadal sex hormones underlie the sexual dimorphic differences in Nf1 optic glioma-induced retinal dysfunction by operating at the level of tumor-associated microglial activation.

  17. Infrared neural stimulation (INS) inhibits electrically evoked neural responses in the deaf white cat

    Science.gov (United States)

    Richter, Claus-Peter; Rajguru, Suhrud M.; Robinson, Alan; Young, Hunter K.

    2014-03-01

    Infrared neural stimulation (INS) has been used in the past to evoke neural activity from hearing and partially deaf animals. All the responses were excitatory. In Aplysia californica, Duke and coworkers demonstrated that INS also inhibits neural responses [1], which similar observations were made in the vestibular system [2, 3]. In deaf white cats that have cochleae with largely reduced spiral ganglion neuron counts and a significant degeneration of the organ of Corti, no cochlear compound action potentials could be observed during INS alone. However, the combined electrical and optical stimulation demonstrated inhibitory responses during irradiation with infrared light.

  18. Filling in the retinal image

    Science.gov (United States)

    Larimer, James; Piantanida, Thomas

    1990-01-01

    The optics of the eye form an image on a surface at the back of the eyeball called the retina. The retina contains the photoreceptors that sample the image and convert it into a neural signal. The spacing of the photoreceptors in the retina is not uniform and varies with retinal locus. The central retinal field, called the macula, is densely packed with photoreceptors. The packing density falls off rapidly as a function of retinal eccentricity with respect to the macular region and there are regions in which there are no photoreceptors at all. The retinal regions without photoreceptors are called blind spots or scotomas. The neural transformations which convert retinal image signals into percepts fills in the gaps and regularizes the inhomogeneities of the retinal photoreceptor sampling mosaic. The filling-in mechamism plays an important role in understanding visual performance. The filling-in mechanism is not well understood. A systematic collaborative research program at the Ames Research Center and SRI in Menlo Park, California, was designed to explore this mechanism. It was shown that the perceived fields which are in fact different from the image on the retina due to filling-in, control some aspects of performance and not others. Researchers have linked these mechanisms to putative mechanisms of color coding and color constancy.

  19. Retinal implants: a systematic review.

    Science.gov (United States)

    Chuang, Alice T; Margo, Curtis E; Greenberg, Paul B

    2014-07-01

    Retinal implants present an innovative way of restoring sight in degenerative retinal diseases. Previous reviews of research progress were written by groups developing their own devices. This systematic review objectively compares selected models by examining publications describing five representative retinal prostheses: Argus II, Boston Retinal Implant Project, Epi-Ret 3, Intelligent Medical Implants (IMI) and Alpha-IMS (Retina Implant AG). Publications were analysed using three criteria for interim success: clinical availability, vision restoration potential and long-term biocompatibility. Clinical availability: Argus II is the only device with FDA approval. Argus II and Alpha-IMS have both received the European CE Marking. All others are in clinical trials, except the Boston Retinal Implant, which is in animal studies. Vision restoration: resolution theoretically correlates with electrode number. Among devices with external cameras, the Boston Retinal Implant leads with 100 electrodes, followed by Argus II with 60 electrodes and visual acuity of 20/1262. Instead of an external camera, Alpha-IMS uses a photodiode system dependent on natural eye movements and can deliver visual acuity up to 20/546. Long-term compatibility: IMI offers iterative learning; Epi-Ret 3 is a fully intraocular device; Alpha-IMS uses intraocular photosensitive elements. Merging the results of these three criteria, Alpha-IMS is the most likely to achieve long-term success decades later, beyond current clinical availability.

  20. Retinal prosthesis for the blind.

    Science.gov (United States)

    Margalit, Eyal; Maia, Mauricio; Weiland, James D; Greenberg, Robert J; Fujii, Gildo Y; Torres, Gustavo; Piyathaisere, Duke V; O'Hearn, Thomas M; Liu, Wentai; Lazzi, Gianluca; Dagnelie, Gislin; Scribner, Dean A; de Juan, Eugene; Humayun, Mark S

    2002-01-01

    Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at different locations along the visual pathways within the central nervous system. The different designs of visual prostheses are named according to their locations (i.e., cortical, optic nerve, subretinal, and epiretinal). Visual loss caused by outer retinal degeneration in diseases such as retinitis pigmentosa or age-related macular degeneration can be reversed by electrical stimulation of the retina or the optic nerve (retinal or optic nerve prostheses, respectively). On the other hand, visual loss caused by inner or whole thickness retinal diseases, eye loss, optic nerve diseases (tumors, ischemia, inflammatory processes etc.), or diseases of the central nervous system (not including diseases of the primary and secondary visual cortices) can be reversed by a cortical visual prosthesis. The intent of this article is to provide an overview of current and future concepts of retinal and optic nerve prostheses. This article will begin with general considerations that are related to all or most of visual prostheses and then concentrate on the retinal and optic nerve designs. The authors believe that the field has grown beyond the scope of a single article so cortical prostheses will be described only because of their direct effect on the concept and technical development of the other prostheses, and this will be done in a more general and historic perspective.

  1. ServCat Document Selection Guidelines

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The ServCat document selection guidelines were developed for selecting appropriate documents to upload into ServCat. When beginning to upload documents into ServCat,...

  2. College Students and Their Cats

    Science.gov (United States)

    Weinstein, Lawrence; Alexander, Ralph

    2010-01-01

    Twenty-two Siamese and 32 mixed breed cats' personalities were rated by their respective college student owners and compared. Further, the owners' self rated personality traits were correlated with the pets'; significant Siamese and Mixed differences and correlations were obtained. These are the first data to examine breed of cat on a personality…

  3. CONTRACT ADMINISTRATIVE TRACKING SYSTEM (CATS)

    Science.gov (United States)

    The Contract Administrative Tracking System (CATS) was developed in response to an ORD NHEERL, Mid-Continent Ecology Division (MED)-recognized need for an automated tracking and retrieval system for Cost Reimbursable Level of Effort (CR/LOE) Contracts. CATS is an Oracle-based app...

  4. Oral masses in two cats.

    Science.gov (United States)

    Bock, P; Hach, V; Baumgärtner, W

    2011-07-01

    Incisional biopsies from the oral cavity of 2 adult cats were submitted for histological investigation. Cat No. 1 showed a solitary well-circumscribed neoplasm in the left mandible. Cat No. 2 demonstrated a diffusely infiltrating neoplasm in the left maxilla. Both tumors consisted of medium-size epithelial cells embedded in a fibrovascular stroma. The mitotic index was 0 to 1 mitosis per high-power field. The epithelial cells showed an irregular arrangement forming nests or streams in cat No. 1, whereas a palisading growth was noted in cat No. 2. Both tumors, especially that of cat No. 1, showed multifocal accumulations of amyloid as confirmed by Congo red staining and a distinct green birefringence under polarized light, which lacked cytokeratin immunoreactivity as well as and AL and AA amyloid immunoreactivity. In addition, the amyloid in cat No. 2 was positive for the odontogenic ameloblast-associated protein, formerly termed APin. In sum, both cats suffered from an amyloid-producing odontogenic tumor, but their tumors varied with respect to morphology and type of amyloid produced.

  5. Lumbosacral agenesis in a cat

    Directory of Open Access Journals (Sweden)

    Gabrielle C Hybki

    2016-01-01

    Full Text Available Case summary Lumbosacral agenesis is a rare congenital condition reported in children. We report a 17-week-old female domestic shorthair cat with lumbosacral agenesis on whole-body radiographs. The cat was euthanized shortly thereafter presentation. A necropsy was not permitted. Relevance and novel information This is the first reported feline case of lumbosacral agenesis.

  6. CAT-generation of ideals

    CERN Document Server

    Ueckerdt, Torsten

    2010-01-01

    We consider the problem of generating all ideals of a poset. It is a long standing open problem, whether or not the ideals of any poset can be generated in constant amortized time, CAT for short. We refine the tree traversal, a method introduced by Pruesse and Ruskey in 1993, to obtain a CAT-generator for two large classes of posets: posets of interval dimension at most two and so called locally planar posets. This includes all posets for which a CAT-generator was known before. Posets of interval dimension at most two generalize both, interval orders and 2-dimensional posets. Locally planar posets generalize for example posets with a planar cover graph. We apply our results to CAT-generate all $c$-orientations of a planar graph. As a special case this is a CAT-generator for many combinatorial objects like domino and lozenge tilings, planar spanning trees, planar bipartite perfect matchings, Schnyder woods, and others.

  7. Effects of haloperidol and phentolamine on the crustacean cardiac ganglion.

    Science.gov (United States)

    Berlind, A

    2001-09-01

    Haloperidol (a dopamine D2 blocker in vertebrates) and phentolamine (an alpha-adrenergic blocker) alter the pattern of bursting by the isolated cardiac ganglion of the lobster when perfused at concentrations of 10(-6)-10(-5) mol/l. Both drugs decrease the frequency of bursting and increase burst duration. They are most effective in slowing the ganglion when applied selectively to the anterior ganglionic trunk, the same region of the ganglion where dopamine (DA) and 5-hydroxytryptamine (5HT) are most effective in speeding up bursting. When exogenous monoamine transmitters are applied in the presence of 3x10(-6) mol/l haloperidol, the effect of 5HT, but not of DA, is significantly reduced. At the same concentration, phentolamine does not suppress the actions of DA, 5HT or noradrenaline (NA). Both haloperidol and phentolamine significantly alter the properties of endogenous burst-organizing potentials (driver potentials) generated by motorneurons in the ganglion. It is possible that the effects of these drugs on bursting reflect alteration of endogenous electrical properties of the constituent neurons, rather than receptor antagonism.

  8. The Grueneberg ganglion: a novel sensory system in the nose.

    Science.gov (United States)

    Fleischer, Joerg; Breer, Heinz

    2010-07-01

    Within the nasal epithelium of mammals, there are several compartments which are populated with neuronal cells. One of them - the so-called Grueneberg ganglion - is composed of ciliated neurons residing in the anterior region of the nose. Although cells of the Grueneberg ganglion lack direct contact with the lumen of the nasal cavity, they are endowed with features indicative of olfactory sensory neurons, such as the olfactory marker protein and distinct olfactory receptors, as well as projection of axonal processes to the olfactory bulb of the brain. These findings have led to the notion that the Grueneberg ganglion might be a novel olfactory subsystem; a concept which was lately supported by the observation that chemical cues activate Grueneberg ganglion neurons. Unexpectedly, it was recently found that these cells also respond to cool ambient temperatures, presumably via a signaling pathway mediated by second messengers. Thus, the Grueneberg ganglion may operate as a dual sensory organ involved in the detection of both chemical and thermal stimuli.

  9. Stereology of the pterygopalatine ganglion of the rat.

    Science.gov (United States)

    Costa, W S; Morais, R; Mandarim-De-Lacerda, C A

    1992-01-01

    The right pterygopalatine ganglia (PG) of 9 male Wistar-strain rats were dissected, embedded in Epon (3 specimens) or paraffin (6 specimens), and prepared for stereological examination under light microscopy. The perikarya were quantitatively characterized, and the ganglionic volume was determined. Stereology is an efficient method for the quantitative evaluation of the perikarya of the PG. The results(expressed as mean +/- standard deviation) were: a) areal fraction occupied by the perikarya = 53.8 +/- 7.4%; b) the perikaryal surface area per volume = 0.101 +/- 0.013 microns-1; c) the number of perikarya per volume x 10(-5) = 5.26 +/- 0.99 microns-3; d) the mean profile area of the perikarya (apk) = 505.93 +/- 78.29 microns 2; e) the mean perikaryal volume (vpk) = 9,179.33 +/- 1,533.52 microns 3; and f) the ganglionic volume = 0.210 +/- 0.127 mm3. The low coefficient of variation the apk and vpk values suggests the presence of only one population of neurons in the PG of the rat. The number of perikarya in the PG is about 11,046 per ganglion. As compared to analogous data in the otic ganglion of the rat, the PG did not show statistically significant stereological differences, but the relatively higher number of neurons found in the PG is probably associated with the higher functional activity of this ganglion.

  10. Characterizing and modeling the intrinsic light response of rat ganglion-cell photoreceptors.

    Science.gov (United States)

    Walch, Olivia J; Zhang, L Samantha; Reifler, Aaron N; Dolikian, Michael E; Forger, Daniel B; Wong, Kwoon Y

    2015-11-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate both image-forming vision and non-image-forming visual responses such as pupillary constriction and circadian photoentrainment. Five types of ipRGCs, named M1-M5, have been discovered in rodents. To further investigate their photoresponse properties, we made multielectrode array spike recordings from rat ipRGCs, classified them into M1, M2/M4, and M3/M5 clusters, and measured their intrinsic, melanopsin-based responses to single and flickering light pulses. Results showed that ipRGC spiking can track flickers up to ∼0.2 Hz in frequency and that flicker intervals between 5 and 14 s evoke the most spikes. We also learned that melanopsin's integration time is intensity and cluster dependent. Using these data, we constructed a mathematical model for each cluster's intrinsic photoresponse. We found that the data for the M1 cluster are best fit by a model that assumes a large photoresponse, causing the cell to enter depolarization block. Our models also led us to hypothesize that the M2/M4 and M3/M5 clusters experience comparable photoexcitation but that the M3/M5 cascade decays significantly faster than the M2/M4 cascade, resulting in different response waveforms between these clusters. These mathematical models will help predict how each ipRGC cluster might respond to stimuli of any waveform and could inform the invention of lighting technologies that promote health through melanopsin stimulation.

  11. Toxoplasmosis : Beware of Cats !!!

    Directory of Open Access Journals (Sweden)

    Rubina Kumari Baithalu

    2010-10-01

    Full Text Available Anthropozoonotic parasite Toxoplasma gondii causes widespread human and animal diseases, mostly involving central nervous system. Human acquires toxoplasmosis from cats, from consuming raw or undercooked meat and from vertical transmission to the fetus through placenta from mother during pregnancy. Socio-epidemiological as well as unique environmental factors also plays a significant role in transmission of this infection. Preventive measures should be taken into account the importance of culture, tradition, and beliefs of people in various communities more than solving poverty and giving health education. Therefore the focus of this article is to create public awareness regarding sense of responsibility of looking after pets to prevent such an important zoonotic disease. [Vet. World 2010; 3(5.000: 247-249

  12. Retinal vascular oximetry during ranibizumab treatment of central retinal vein occlusion

    DEFF Research Database (Denmark)

    Traustason, Sindri; la Cour, Morten; Larsen, Michael

    2014-01-01

    PURPOSE: To investigate the effect of intravitreal injections of the vascular endothelial growth factor inhibitor ranibizumab on retinal oxygenation in patients with central retinal vein occlusion (CRVO). METHODS: Retinal oxygen saturation in patients with CRVO was analysed using the Oxymap Retin...

  13. 促红细胞生成素及其受体与视神经视网膜疾病%The protective effects of erythropoietin/erythropoietin receptor system on optic nerve and retinal diseases

    Institute of Scientific and Technical Information of China (English)

    解正高; 庄朝荣

    2011-01-01

    Erythropoietin(EPO) has an anti-apoptotic effect,and promotes the proliferation and differentiation of erythroid progenitor cells. Several studies have indicated that EPO can protect photoreceptor cells from the lightinduced retinal degeneration ;protect retinal neurons from ischemia-reperfusion injury and retinal ganglion cells after acute and chronic ocular hypertension; promote ganglion cell survival and axonal regeneration after optic nerve transaction; attenuate inflammation in multiple sclerosis optic neuritis; reduce the permeability of the retinal barrier and protect retinal neurons in diabetic retinopathy; enhance the stability of hypoxic retinal vessels in retinopathy of prematurity. Herein,we review the distribution of EPO and its receptor in retina,their expression in animal model of retinal diseases,and their effects and mechanisms in protection of retinal neurons and optic nerve.%促红细胞生成素(EPO)具有促进红系祖细胞增生和分化的作用,其在光诱导性视网膜变性、视网膜缺血-再灌注损伤、急慢性高眼压、视神经损伤、多发性硬化性视神经炎、糖尿病视网膜病变(DR)、早产儿视网膜病变(ROP)等视神经视网膜疾病模型中的神经保护作用也受到了关注.就EPO及其受体在视网膜的分布、其在视神经视网膜病变模型中的表达情况及其对视网膜神经元的保护作用和机制方面的研究进展进行综述.

  14. Expression patterns of the retinal development-related genes in the fetal and adult retina

    Institute of Scientific and Technical Information of China (English)

    LI Hui-ming; WANG Feng; QIU Wei; LIU Yan; HUANG Qian

    2007-01-01

    Background Retina is important in converting light into neural signals, but little is known about the regulatory genes essential for the retinal morphological formation, development and functional differentiation. This study aimed to investigate the mRNA expression patterns and cellular or subcellular distribution of 33 differentially expressed genes in the retina belonging to the early and middle-late embryogenesis stages as well as the early adult stage during human development.Methods In situ hybridization and real-time fluorescent quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) were used to assay 33 differentially expressed genes which were screened out using microarray analysis and were not present in the retinal cDNA or the Expressed Sequence Tags (EST) database of the National Eye Institute (NEI) Genebank.Results Nine of the 33 genes belonged to EST or the unknown cDNA fragments, and the remaining belonged to the novel genes in the retina. During the human retinal development 17 genes were down-regulated, 6 were up-regulated and the remaining 10 were relatively unchanged. Most of the genes expressed in all layers of the retina at the gestation stage, and in the fully developed retina some genes examined did show higher expression level in certain specific cells and structures such as retinal ganglion cells or the outer segment of photoreceptor cells.Conclusion The gene expression profile during retinal development possesses temporal and spatial distribution features, which can provide experimental evidence for further research of the functions of those genes.

  15. Imaging demonstration of fistulous gas communication between joint and ganglion of medial malleolus

    Energy Technology Data Exchange (ETDEWEB)

    Coulier, B. [Department of Diagnostic Imaging, Namur (Belgium); Devyver, B. [Orthopedic Surgery, Namur (Belgium); Hamels, J. [Institute of Pathology and Genetics, Gerpinnes (Belgium)

    2002-01-01

    We report an unusual demonstration of a fistulous gas communication between the ankle joint and ganglion of the medial malleolus. The imaging findings support the mechanical hypothesis for the genesis of intraosseous ganglion cysts. (orig.)

  16. Brain-derived neurotrophic factor and retinal ganglion cells in the retina of diabetic rat after intravitreal injection of human umbilical cord mesenchymal stem cells-induced neural stem cells%玻璃体腔注射人脐带间充质干细胞诱导分化的神经干细胞对糖尿病大鼠视网膜脑源性神经营养因子表达及视网膜神经节细胞计数的影响

    Institute of Scientific and Technical Information of China (English)

    张惟; 王月欣; 陈松; 段红涛; 孔佳慧; 董蒙; 毕雪; 宋建

    2016-01-01

    Objective To investigate the effect of intravitreal injection of neural stem cells (NSC)derived from human umbilical cord mesenchymal stem cells (hUCMSC) on the expression of brain-derived neurotrophic factor (BDNF) and the number of retinal ganglion cells (RGC).Methods Fifty-two adult male Sprague-Dawley rats were randomly divided into normal group (group A) and diabetes mellitus group which received intraperitoneal injection of streptozocin to make diabetic rat models.One month after the diabetic rat models were confirmed successfully,diabetic rats were randomly divided into diabetic group (group B),hUCMSC group (group C) and hUCMSC-induced NSC group (group D).And thirteen diabetic rats were included in each group.Immuno-cytochemistry was applied to observe BDNF and thymosin-1 (Thy-1) staining in the retina.Then mean integrated absorbance of the staining region on the retina slices were analyzed by Image-Pro Plus 6.0.The number of Thy-1 labeled RGC was record.Results BDNF and Thy-1 were positive on the retina slices from group A.The staining intensity from group B became weak and the expression of BDNF and Thy-1 gradually decrease with time (P<0.05),and those from group C and group D were positively (P<0.05),especially in group D (P<0.05).The BDNF expression and Thy-1 labeled RGC were the same between group B and C (P>0.05) at 2 weeks after injection,but were significant different for other time points (P<0.05).Significant positive correlation between the expression of BDNF and the number of RGC were found by the Pearson correlation analysis (r=0.964,P<0.05).Conclusion Intravitreal injection of hUCMSC-derived NSC to diabetic rat may protect the retina by promoting the expression of BDNF and increasing the number of RGC.%目的 观察玻璃体腔注射人脐带间充质干细胞(hUCMSC)诱导分化的神经干细胞(NSC)对糖尿病大鼠视网膜脑源性神经营养因子(BDNF)表达及视网膜神经节细胞计数(RGC)的影响.方法

  17. [Congenital retinal folds in different clinical cases].

    Science.gov (United States)

    Munteanu, M

    2005-01-01

    We present 12 clinical cases of congenital retinal folds with different etiologies: posterior primitive vitreous persistency and hyperplasia (7 cases),retinocytoma (1 case). retinopathy of prematurity (1 case), astrocytoma of the retina (1 case), retinal vasculitis (1 case), Goldmann-Favre syndrome (1 case). Etiopathogenic and nosological aspects are discussed; the congenital retinal folds are interpreted as a symptom in a context of a congenital or acquired vitreo-retinal pathology.

  18. Pemphigus foliaceus in a cat.

    Science.gov (United States)

    Kofod, H

    1993-01-16

    The author's cat started to develop the signs of pemphigus foliaceus one month after he returned home after six months absence. The initial signs included dry coughing and difficulty with purring and swallowing, followed by typical changes of the skin. The cat was treated by a combination of chrysotherapy and systemic glucocorticoid injections, and remained free of clinical signs for one and a half years. The cat then relapsed and showed the initial signs except that coughing was not observed. It was treated as before but after a second relapse and the same treatment it slowly developed a general weakness and was euthanased.

  19. Ganglion Cyst Associated with Triangular Fibrocartilage Complex Tear That Caused Ulnar Nerve Compression

    OpenAIRE

    2015-01-01

    Summary: Ganglions are the most frequently seen soft-tissue tumors in the hand. Nerve compression due to ganglion cysts at the wrist is rare. We report 2 ganglion cysts arising from triangular fibrocartilage complex, one of which caused ulnar nerve compression proximal to the Guyon's canal, leading to ulnar neuropathy. Ganglion cysts seem unimportant, and many surgeons refrain from performing a general hand examination.

  20. Ganglion Cyst Associated with Triangular Fibrocartilage Complex Tear That Caused Ulnar Nerve Compression

    Directory of Open Access Journals (Sweden)

    Ugur Anil Bingol, MD

    2015-03-01

    Full Text Available Summary: Ganglions are the most frequently seen soft-tissue tumors in the hand. Nerve compression due to ganglion cysts at the wrist is rare. We report 2 ganglion cysts arising from triangular fibrocartilage complex, one of which caused ulnar nerve compression proximal to the Guyonʼs canal, leading to ulnar neuropathy. Ganglion cysts seem unimportant, and many surgeons refrain from performing a general hand examination.

  1. Morphology, topography and cytoarchitectonics of the otic ganglion in Egyptian spiny mouse (Acomys cahirinus, Desmarest).

    Science.gov (United States)

    Szczurkowski, A; Kuder, T; Nowak, E; Kuchinka, J

    2001-01-01

    Using the thiocholine method of Koelle and Friedenwald and histological techniques, the otic ganglion in Egyptian spiny mouse (Acomys cahirinus, Desmarest) was studied. The ganglion was found to be a single oval cluster of neurocytes, situated at the medial and posterior surface of the mandibular nerve just above the maxillary artery. The ganglion is composed of typical ganglionic neurons in compact arrangement without a thick connective-tissue capsule.

  2. Morphology, topography and cytoarchitectonics of the pterygopalatine ganglion in Egyptian spiny mouse (Acomys cahirinus, Desmarest).

    Science.gov (United States)

    Szczurkowski, Aleksander; Kuder, Tadeusz; Nowak, Elzbieta; Kuchinka, Jacek

    2002-01-01

    Using the thiocholine method of Koelle and Friedenwald and histological techniques the pterygopalatine ganglion in Egyptian spiny mouse (Acomys cahirinus, Desmarest) was studied. The ganglion was found to be a single irregular cluster of neurocytes, situated on the medial surface of the maxillary nerve. The ganglion is composed of oval, elliptical and sometimes fusiform ganglionic neurones in compact arrangement without a thick connective-tissue capsule.

  3. Choroidal melanoma clinically simulating a retinal angioma

    Energy Technology Data Exchange (ETDEWEB)

    Shields, J.A.; Joffe, L.; Guibor, P.

    1978-01-01

    An amelanotic fundus lesion in a 35-year-old man was associated with a dilated retinal vessel, thus suggesting the diagnosis of retinal angioma. Fluorescein angiography and B-scan ultrasonography were not diagnostic, but a radioactive phosphorus uptake test suggested the lesion was malignant. The enucleated globe showed a malignant choroidal melanoma drained by a large retinal vein.

  4. Choroidal melanoma clinically simulating a retinal angioma.

    Science.gov (United States)

    Shields, J A; Joffe, L; Guibor, P

    1978-01-01

    An amelanotic fundus lesion in a 35-year-old man was associated with a dilated retinal vessel, thus suggesting the diagnosis of retinal angioma. Fluorescein angiography and B-scan ultrasonography were not diagnostic, but a radioactive phosphorus uptake test suggested the lesion was malignant. The enucleated globe showed a malignant choroidal melanoma drained by a large retinal vein.

  5. Compressive neuropathies related to ganglions of the wrist and hand.

    Science.gov (United States)

    Jayakumar, Prakash; Jayaram, Vijay; Nairn, David S

    2014-01-01

    Ganglions of the wrist and hand causing compressive neuropathies are rare clinical entities. Compression of the ulnar and median nerves in their respective fibro-osseous tunnels lead to characteristic patterns of motor and/or sensory deficits, which are directly related to the location of the lesion. We present a unique case of a "dumbbell" shaped ganglion invading both Guyon's canal and the carpal tunnel causing a dual compressive neuropathy of the ulnar and median nerve. We discuss the patho-anatomy, clinical assessment, investigation and surgical treatment of this condition.

  6. A rare case of intraosseous ganglion of the triquetrum

    Directory of Open Access Journals (Sweden)

    Luben Stokov

    2012-03-01

    Full Text Available Carpal intraosseous ganglia are one of the rarely seenpathologic conditions in the hand. In this report we presenta rare case of an intraosseous ganglion cyst in a16-year-old girl located in the triquetrum bone as an uncommoncause of wrist pain. Radiographic and magneticresonance imaging demonstrated the cystic lesion intothe triquetrum. The patient was successfully treated byexcision of the ganglion cyst and curettage of the bone.Clinical aspects, radiological findings and treatment modalitiesof this condition were briefly reviewed. J Clin ExpInvest 2012; 3(1: 111-112

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