The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina

Energy Technology Data Exchange (ETDEWEB)

Tao, Ye [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China); Chen, Tao [Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi' an 710032 (China); Liu, Bei [Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi' an (China); Yang, Guo Qing [Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi' an 710032 (China); Peng, Guanghua [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China); Zhang, Hua [Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi' an (China); Huang, Yi Fei [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China)

2015-07-01

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. - Highlights: • We systemically explored the neural activities and visual signal pathways of MNU administrated retinas. • The focal photoreceptors had different vulnerabilities to the MNU administration. �

The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina

International Nuclear Information System (INIS)

Tao, Ye; Chen, Tao; Liu, Bei; Yang, Guo Qing; Peng, Guanghua; Zhang, Hua; Huang, Yi Fei

2015-01-01

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. - Highlights: • We systemically explored the neural activities and visual signal pathways of MNU administrated retinas. • The focal photoreceptors had different vulnerabilities to the MNU administration. �

Information processing in the outer retina of fish

NARCIS (Netherlands)

Endeman, D.

2017-01-01

The retina translates light into neuronal activity. Thus, it renders visual information of the external environment. The retina can only send a limited amount of information to the brain within a given period. To use this amount optimally, light stimuli are strongly processed in the retina. This

Cellular disturbance in the rats retina after irradiation and metabolic errors during the postnatal period

International Nuclear Information System (INIS)

Lierse, W.; Franke, H.D.

1982-01-01

During the first five days of the postnatal period the retina has been vulnerable following administration of DNA blocking drugs and irradiation with conventional X-rays and fast neutrons. During this period the disturbance of lamination accompanied with pycnosis of neurons and neuroblasts has been the important morphologic reaction. During the same phase metabolic errors, like experimental phenylketonuria, have produced a swelling of photoreceptor cells and pigmentepithelium cells. The other neurons of the retina were pycnotic. Structural alterations like rosettes persisted during the rest of life. The relative minor error during the first phase of rats life may result in a persistent disease. (orig.)

An analog silicon retina with multichip configuration.

Science.gov (United States)

Kameda, Seiji; Yagi, Tetsuya

2006-01-01

The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

The retina

DEFF Research Database (Denmark)

van Reyk, David M; Gillies, Mark C; Davies, Michael Jonathan

2003-01-01

A prominent and early feature of the retinopathy of diabetes mellitus is a diffuse increase in vascular permeability. As the disease develops, the development of frank macular oedema may result in vision loss. That reactive oxygen species production is likely to be elevated in the retina, and tha...

The infrared retina

International Nuclear Information System (INIS)

Krishna, Sanjay

2009-01-01

As infrared imaging systems have evolved from the first generation of linear devices to the second generation of small format staring arrays to the present 'third-gen' systems, there is an increased emphasis on large area focal plane arrays (FPAs) with multicolour operation and higher operating temperature. In this paper, we discuss how one needs to develop an increased functionality at the pixel level for these next generation FPAs. This functionality could manifest itself as spectral, polarization, phase or dynamic range signatures that could extract more information from a given scene. This leads to the concept of an infrared retina, which is an array that works similarly to the human eye that has a 'single' FPA but multiple cones, which are photoreceptor cells in the retina of the eye that enable the perception of colour. These cones are then coupled with powerful signal processing techniques that allow us to process colour information from a scene, even with a limited basis of colour cones. Unlike present day multi or hyperspectral systems, which are bulky and expensive, the idea would be to build a poor man's 'infrared colour' camera. We use examples such as plasmonic tailoring of the resonance or bias dependent dynamic tuning based on quantum confined Stark effect or incorporation of avalanche gain to achieve embodiments of the infrared retina.

Retina neural circuitry seen with particle detector technology

CERN Multimedia

CERN Bulletin

2010-01-01

Using particle physics techniques, high energy physics researchers have recently provided new insight into neural circuits inside the retina. After uncovering a new type of retinal cell and mapping how the retina deals with colours, the team from Santa Cruz (US), Krakow and Glasgow is now turning its attention to more complex issues such as how the retina gets wired up and how the brain deals with the signals it receives from the retina. All this using technology derived from high-density, multistrip silicon detectors…   Seen from the point of view of a particle physicist, eyes are image detectors that can gather many different types of data: light and dark, different colours, motion, etc. In particular, the retina, a thin tissue that lines the back of the eye, is a biological pixel detector that detects light and converts it to electrical signals that travel through the optic nerve to the brain. Neurobiologists know that many different cell types are involved in these processes, but they...

Radioadaptive Cytoprotective Pathways in the Mouse Retina

Science.gov (United States)

Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.

2010-01-01

Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

Assessment of apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy after grape polyphenols intervention

Institute of Scientific and Technical Information of China (English)

Sheng-Li Zhang

2016-01-01

Objective:To study the effect of grape polyphenols intervention on apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy (DR).Methods: SPF male SD rats were selected as experimental animals and divided into control group, diabetes group and grape polyphenols group, intraperitoneal injection of streptozotocin was adopted to establish diabetic rat models, and grape polyphenols group received intragastric administration of grape polyphenols. 60 d after model establishment, the rats were executed, and the retina tissue was collected to determine apoptosis molecules and oxidative stress indexes.Results:Bax, Caspase-3, c-fos, c-jun, ROS, MDA, 8-OHdG, PARP, Cyclophilin D, Nrf-2, ARE, ERK and PI3K content in retina tissue of diabetes group were significantly higher than those of control group while Bcl-2, CAT, SOD, GSH-Px, HO-1 and NQO1 content were significantly lower than those of control group; Bax, Caspase-3, c-fos, c-jun, ROS, MDA, 8-OHdG, PARP and Cyclophilin D content in retina tissue of grape polyphenols group were significantly lower than those of diabetes group while Bcl-2, CAT, SOD, GSH-Px, HO-1, NQO1, Nrf-2, ARE, ERK and PI3K content were significantly higher those of diabetes group.Conclusions:Grape polyphenols intervention can relieve the apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy.

Retina image–based optic disc segmentation

Directory of Open Access Journals (Sweden)

Ching-Lin Wang

2016-05-01

Full Text Available The change of optic disc can be used to diagnose many eye diseases, such as glaucoma, diabetic retinopathy and macular degeneration. Moreover, retinal blood vessel pattern is unique for human beings even for identical twins. It is a highly stable pattern in biometric identification. Since optic disc is the beginning of the optic nerve and main blood vessels in retina, it can be used as a reference point of identification. Therefore, optic disc segmentation is an important technique for developing a human identity recognition system and eye disease diagnostic system. This article hence presents an optic disc segmentation method to extract the optic disc from a retina image. The experimental results show that the optic disc segmentation method can give impressive results in segmenting the optic disc from a retina image.

The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina.

Science.gov (United States)

Tao, Ye; Chen, Tao; Liu, Bei; Yang, Guo Qing; Peng, Guanghua; Zhang, Hua; Huang, Yi Fei

2015-07-01

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. Copyright © 2015 Elsevier Inc. All rights reserved.

Imaging of the peripheral retina

Directory of Open Access Journals (Sweden)

Marcus Kernt

2013-01-01

Full Text Available The technical progress of the recent years has revolutionized imaging in ophthalmology. Scanning laser ophthalmoscopy (SLO, digital angiography, optical coherence tomography (OCT, and detection of fundus autofluorescence (FAF have fundamentally changed our understanding of numerous retinal and choroidal diseases. Besides the tremendous advances in macular diagnostics, there is more and more evidence that central pathologies are often directly linked to changes in the peripheral retina. This review provides a brief overview on current posterior segment imaging techniques with a special focus on the peripheral retina.

Imagen de retina de campo ultra-amplio

Directory of Open Access Journals (Sweden)

Gerardo García-Aguirre

2017-11-01

Conclusión: Las imágenes de campo ultra-amplio han revolucionado la forma en la que estudiamos y entendemos la enfermedad de la retina. A medida que la tecnología para obtenerlas se haga más accesible, formará parte del armamentario de rutina para estudiar las enfermedades de la retina.

Topography of ganglion cell production in the cat's retina

International Nuclear Information System (INIS)

Walsh, C.; Polley, E.H.

1985-01-01

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

Helping the Retina Regenerate

Science.gov (United States)

... the retina News Brief 03/30/17 A new report gives recommendations for regenerating retinal ganglion cells (RGCs), crucial neurons in the back of the eye that carry visual information to the brain. Authored ...

Meduloepitelioma teratóide da retina: relato de caso Teratoid medulloepithelioma of the retina: case report

Directory of Open Access Journals (Sweden)

Ramon Coral Ghanem

2004-06-01

Full Text Available O meduloepitelioma é um tumor intra-ocular congênito originário do epitélio medular primitivo que, por sua vez, é responsável pela formação do epitélio não pigmentado do corpo ciliar. Ocorre geralmente na infância, de forma unilateral, acometendo o corpo ciliar. O objetivo deste trabalho é documentar um caso raro de meduloepitelioma teratóide originário da retina. Paciente de nove anos, feminina, apresentava baixa acuidade visual (AV, estrabismo e leucocoria no olho esquerdo (OE. A AV era de 1,0 no olho direito e movimentos de mão no OE. Foi observada tumoração retrocristaliniana branco-acinzentada no OE, aparentemente subretiniana, vascularizada, de grande extensão, com alterações císticas na sua superfície. Foram realizadas tomografia de crânio e órbitas e ecografia ocular. A paciente foi submetida à enucleação com suspeita clínica de retinoblastoma. Pelo aspecto histopatológico foi feito o diagnóstico de meduloepitelioma teratóide benigno originário da retina. Na maioria dos casos apresentados na literatura o meduloepitelioma tem origem a partir do epitélio não pigmentado do corpo ciliar. No nosso caso, a neoplasia parece ter tido origem a partir da retina, já que os cortes revelaram epitélio do corpo ciliar preservado e não foi reconhecida a estrutura normal da retina. Embora o tumor apresentado neste relato tenha sido classificado como benigno, o fato de ser lesão de grandes proporções e de crescimento aparentemente recente, justifica a conduta cirúrgica empregada. O tratamento do meduloepitelioma deve objetivar a intervenção cirúrgica precoce, na tentativa de se evitar a disseminação extra-ocular.Medulloepithelioma is a congenital intraocular tumor that usually arises from the primitive medullary epithelium that is destined to form the nonpigmented ciliary epithelium of the ciliary body. It occurs most frequently in early childhood and is unilateral. This report documents a rare case of

Why has Nature Chosen Lutein and Zeaxanthin to Protect the Retina?

OpenAIRE

Widomska, Justyna; Subczynski, Witold K

2014-01-01

Age-related macular degeneration (AMD) is associated with a low level of macular carotenoids in the eye retina. Only two carotenoids, namely lutein and zeaxanthin are selectively accumulated in the human eye retina from blood plasma where more than twenty other carotenoids are available. The third carotenoid which is found in the human retina, meso-zeaxanthin is formed directly in the retina from lutein. All these carotenoids, named also macular xanthophylls, play key roles in eye health and ...

Rhythmic ganglion cell activity in bleached and blind adult mouse retinas.

Science.gov (United States)

Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

2014-01-01

In retinitis pigmentosa--a degenerative disease which often leads to incurable blindness--the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor's dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the understanding of the degeneration process and may guide future rescue strategies.

Counteracting Animal Homelessness and Providing Care for Stray Animals as a Task of a Commune

OpenAIRE

Szalewska, Małgorzata

2017-01-01

The analysis of Polish binding law acts allows one to assume that, on normative level, the obligation of public administration to provide care for stray animals is deeply embedded. Both the Animal Protection Act, as well as the Act on Maintaining Cleanliness, indicate the tasks of a commune in the scope of providing care for stray animals, catching homeless animals and counteracting their homelessness. Simultaneously, the analysis of jurisdiction, and inquiries as well as considerations emerg...

Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina.

Directory of Open Access Journals (Sweden)

Hideto Osada

Full Text Available Excessive exposure to light promotes degenerative and blinding retinal diseases such as age-related macular degeneration and retinitis pigmentosa. However, the underlying mechanisms of photo-induced retinal degeneration are not fully understood, and a generalizable preventive intervention has not been proposed. Bilberry extract is an antioxidant-rich supplement that ameliorates ocular symptoms. However, its effects on photo-stressed retinas have not been clarified. In this study, we examined the neuroprotective effects of bilberry extract against photo-stress in murine retinas. Light-induced visual function impairment recorded by scotopic and phototopic electroretinograms showing respective rod and cone photoreceptor function was attenuated by oral administration of bilberry extract through a stomach tube in Balb/c mice (750 mg/kg body weight. Bilberry extract also suppressed photo-induced apoptosis in the photoreceptor cell layer and shortening of the outer segments of rod and cone photoreceptors. Levels of photo-induced reactive oxygen species (ROS, oxidative and endoplasmic reticulum (ER stress markers, as measured by real-time reverse transcriptase polymerase chain reaction, were reduced by bilberry extract treatment. Reduction of ROS by N-acetyl-L-cysteine, a well-known antioxidant also suppressed ER stress. Immunohistochemical analysis of activating transcription factor 4 expression showed the presence of ER stress in the retina, and at least in part, in Müller glial cells. The photo-induced disruption of tight junctions in the retinal pigment epithelium was also attenuated by bilberry extract, repressing an oxidative stress marker, although ER stress markers were not repressed. Our results suggest that bilberry extract attenuates photo-induced apoptosis and visual dysfunction most likely, and at least in part, through ROS reduction, and subsequent ER stress attenuation in the retina. This study can help understand the mechanisms of photo

[Degenerative lesions of the peripheral retina].

Science.gov (United States)

Conart, J-B; Baron, D; Berrod, J-P

2014-01-01

Degenerative lesions of the peripheral retina are present from teenage years onwards and increase with age. These abnormabilities are frequent, some of them being benign while others predispose to retinal tears and detachment. In the latter case, the lesions are rhegmatogenous and may justify prophylactic treatment by laser photocoagulation. We distinguish congenital lesions of the peripheral retina and intraretinal, chorioretinal and vitreoretinal degenerations. The holes and tears observed in 2% of the population consist of round atrophic holes, "horseshoe" tears, oral dialyses and giant tears. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

FPGA-Based Real Time, Multichannel Emulated-Digital Retina Model Implementation

Directory of Open Access Journals (Sweden)

Zsolt Vörösházi

2009-01-01

Full Text Available The function of the low-level image processing that takes place in the biological retina is to compress only the relevant visual information to a manageable size. The behavior of the layers and different channels of the neuromorphic retina has been successfully modeled by cellular neural/nonlinear networks (CNNs. In this paper, we present an extended, application-specific emulated-digital CNN-universal machine (UM architecture to compute the complex dynamic of this mammalian retina in video real time. The proposed emulated-digital implementation of multichannel retina model is compared to the previously developed models from three key aspects, which are processing speed, number of physical cells, and accuracy. Our primary aim was to build up a simple, real-time test environment with camera input and display output in order to mimic the behavior of retina model implementation on emulated digital CNN by using low-cost, moderate-sized field-programmable gate array (FPGA architectures.

Neurotransmitter properties of the newborn human retina

International Nuclear Information System (INIS)

Hollyfield, J.G.; Frederick, J.M.; Rayborn, M.E.

1983-01-01

Human retinal tissue from a newborn was examined autoradiographically for the presence of high-affinity uptake and localization of the following putative neurotransmitters: dopamine, glycine, GABA, aspartate, and glutamate. In addition, the dopamine content of this newborn retina was measured by high pressure liquid chromatography. Our study reveals that specific uptake mechanisms for 3 H-glycine, 3 H-dopamine, and 3 H-GABA are present at birth. However, the number and distribution of cells labeled with each of these 3 H-transmitters are not identical to those observed in adult human retinas. Furthermore, the amount of endogenous dopamine in the newborn retina is approximately 1/20 the adult level. Photoreceptor-specific uptake of 3 H-glutamate and 3 H-aspartate are not observed. These findings indicate that, while some neurotransmitter-specific properties are present at birth, significant maturation of neurotransmitter systems occurs postnatally

A digital retina-like low-level vision processor.

Science.gov (United States)

Mertoguno, S; Bourbakis, N G

2003-01-01

This correspondence presents the basic design and the simulation of a low level multilayer vision processor that emulates to some degree the functional behavior of a human retina. This retina-like multilayer processor is the lower part of an autonomous self-organized vision system, called Kydon, that could be used on visually impaired people with a damaged visual cerebral cortex. The Kydon vision system, however, is not presented in this paper. The retina-like processor consists of four major layers, where each of them is an array processor based on hexagonal, autonomous processing elements that perform a certain set of low level vision tasks, such as smoothing and light adaptation, edge detection, segmentation, line recognition and region-graph generation. At each layer, the array processor is a 2D array of k/spl times/m hexagonal identical autonomous cells that simultaneously execute certain low level vision tasks. Thus, the hardware design and the simulation at the transistor level of the processing elements (PEs) of the retina-like processor and its simulated functionality with illustrative examples are provided in this paper.

The mammalian retina as a clock

Science.gov (United States)

Tosini, Gianluca; Fukuhara, Chiaki

2002-01-01

Many physiological, cellular, and biochemical parameters in the retina of vertebrates show daily rhythms that, in many cases, also persist under constant conditions. This demonstrates that they are driven by a circadian pacemaker. The presence of an autonomous circadian clock in the retina of vertebrates was first demonstrated in Xenopus laevis and then, several years later, in mammals. In X. laevis and in chicken, the retinal circadian pacemaker has been localized in the photoreceptor layer, whereas in mammals, such information is not yet available. Recent advances in molecular techniques have led to the identification of a group of genes that are believed to constitute the molecular core of the circadian clock. These genes are expressed in the retina, although with a slightly different 24-h profile from that observed in the central circadian pacemaker. This result suggests that some difference (at the molecular level) may exist between the retinal clock and the clock located in the suprachiasmatic nuclei of hypothalamus. The present review will focus on the current knowledge of the retinal rhythmicity and the mechanisms responsible for its control.

Selective retina therapy (SRT)

International Nuclear Information System (INIS)

Brinkmann, R.; Birngruber, R.

2007-01-01

Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Luebeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the choroid. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced. (orig.)

Expression of nitric oxide synthase during the development of RCS rat retinas.

Science.gov (United States)

Sharma, R K; Warfvinge, K; Ehinger, B

2001-01-01

Nitric oxide (NO) has been reported to be both neurodestructive and neuroprotective in the central nervous system and could possibly play an important role in neurodegenerative disorders. On the assumption that NO synthesis may influence degenerative processes in the retina, we have examined the development and distribution of nitric-oxide-synthase(NOS)-immunoreactive cells in developing Royal College of Surgeons (RCS) rat retinas, which is an animal model for retinal degeneration. An antibody against constitutive neuronal NOS was used for immunocytochemistry on RCS rat retinas from postnatal (PN) days 3, 7, 10, 14, 35, 70 and 281 and compared with that in the normal rats of PN days 3, 7, 10, 14, 54 and adults. Immunoreactive cells were not seen in PN 3 retinas but were distinctly seen in the PN 7 retina along with a plexus in the inner plexiform layer. In both groups (normal and RCS rats) a distinct sublayering of the plexus in the inner plexiform layer could be seen at PN 10, which became more distinct at PN 14. The immunoreactive cells were detected also in the oldest retina examined, which was PN 281 in the case of RCS rats. In both groups, certain amacrine cells, certain bipolar cells and certain horizontal cells were found to be immunoreactive. In conclusion, the developmental timetable of the NOS immunoreactivity was identical in the normal and the RCS rat retinas. The NOS-immunoreactive cells persisted in the RCS retinas even when the retina had degenerated extensively. Abnormalities with the inducible isoforms of NOS cannot be ruled out from this study. We conclude that the chronological and qualitative development of the constitutive neuronal NOS immunoreactivity is normal in RCS rat retinas. Copyright 2001 S. Karger AG, Basel

Real-time simulation of the retina allowing visualization of each processing stage

Science.gov (United States)

Teeters, Jeffrey L.; Werblin, Frank S.

1991-08-01

The retina computes to let us see, but can we see the retina compute? Until now, the answer has been no, because the unconscious nature of the processing hides it from our view. Here the authors describe a method of seeing computations performed throughout the retina. This is achieved by using neurophysiological data to construct a model of the retina, and using a special-purpose image processing computer (PIPE) to implement the model in real time. Processing in the model is organized into stages corresponding to computations performed by each retinal cell type. The final stage is the transient (change detecting) ganglion cell. A CCD camera forms the input image, and the activity of a selected retinal cell type is the output which is displayed on a TV monitor. By changing the retina cell driving the monitor, the progressive transformations of the image by the retina can be observed. These simulations demonstrate the ubiquitous presence of temporal and spatial variations in the patterns of activity generated by the retina which are fed into the brain. The dynamical aspects make these patterns very different from those generated by the common DOG (Difference of Gaussian) model of receptive field. Because the retina is so successful in biological vision systems, the processing described here may be useful in machine vision.

Functional Architecture of the Retina: Development and Disease

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Hoon, Mrinalini; Okawa, Haruhisa; Santina, Luca Della; Wong, Rachel O.L.

2014-01-01

Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina. PMID:24984227

Modeling laser damage to the retina

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Clark, Clifton D.

This dissertation presents recent progress in several areas related to modeling laser damage to the retina. In Chapter 3, we consider the consequences of using the Arrhenius damage model to predict the damage thresholds of multiple pulse, or repetitive pulse, exposures. We have identified a few fundamental trends associated with the multiple pulse damage predictions made by the Arrhenius model. These trends differ from what would be expected by non-thermal mechanisms, and could prove useful in differentiating thermal and non-thermal damage. Chapter 4 presents a new rate equation damage model hypothesized to describe photochemical damage. The model adds a temperature dependent term to the simple rate equation implied by the principle of reciprocity that is characteristic of photochemical damage thresholds. A recent damage threshold study, conducted in-vitro, has revealed a very sharp transition between thermal and photochemical damage threshold trends. For the wavelength used in the experiment (413 nm), thermal damage thresholds were observed at exposure levels that were twice the expected photochemical damage threshold, based on the traditional understanding of photochemical damage. Our model accounts for this observed trend by introducing a temperature dependent quenching, or repair, rate to the photochemical damage rate. For long exposures that give a very small temperature rise, the model reduces to the principle of reciprocity. Near the transition region between thermal and photochemical damage, the model allows the damage threshold to be set by thermal mechanisms, even at exposure above the reciprocity exposure. In Chapter 5, we describe a retina damage model that includes thermal lensing in the eye by coupling beam propagation and heat transfer models together. Thermal lensing has recently been suggested as a contributing factor to the large increase in measured retinal damage thresholds in the near infrared. The transmission of the vitreous decreases

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

Illumination-invariant face recognition with a contrast sensitive silicon retina

Energy Technology Data Exchange (ETDEWEB)

Buhmann, J.M. [Rheinische Friedrich-Wilhelms-Univ., Bonn (Germany). Inst. fuer Informatik II; Lades, M. [Bochum Univ. (Germany). Inst. fuer Neuroinformatik; Eeckman, F. [Lawrence Livermore National Lab., CA (United States)

1993-11-29

Changes in lighting conditions strongly effect the performance and reliability of computer vision systems. We report face recognition results under drastically changing lighting conditions for a computer vision system which concurrently uses a contrast sensitive silicon retina and a conventional, gain controlled CCD camera. For both input devices the face recognition system employs an elastic matching algorithm with wavelet based features to classify unknown faces. To assess the effect of analog on-chip preprocessing by the silicon retina the CCD images have been digitally preprocessed with a bandpass filter to adjust the power spectrum. The silicon retina with its ability to adjust sensitivity increases the recognition rate up to 50 percent. These comparative experiments demonstrate that preprocessing with an analog VLSI silicon retina generates image data enriched with object-constant features.

Maturação funcional da retina em bebês prematuros

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Adriana Berezovsky

2007-06-01

Full Text Available A retina humana ainda não está totalmente desenvolvida no nascimento. Só após o nascimento é que ocorrem mudanças anatômicas como o aumento na densidade de cones centrais e o alongamento do segmento externo dos fotorreceptores. As mudanças funcionais que ocorrem na retina com a maturação no primeiro ano de vida podem ser avaliadas pela técnica do eletrorretinograma de campo total, que representa a atividade somada da retina distal em resposta à luz. Abordaremos aspectos da maturação funcional da retina avaliada pelo eletrorretinograma em bebês prematuros.

Connecting the Retina to the Brain

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Lynda Erskine

2014-12-01

Full Text Available The visual system is beautifully crafted to transmit information of the external world to visual processing and cognitive centers in the brain. For visual information to be relayed to the brain, a series of axon pathfinding events must take place to ensure that the axons of retinal ganglion cells, the only neuronal cell type in the retina that sends axons out of the retina, find their way out of the eye to connect with targets in the brain. In the past few decades, the power of molecular and genetic tools, including the generation of genetically manipulated mouse lines, have multiplied our knowledge about the molecular mechanisms involved in the sculpting of the visual system. Here, we review major advances in our understanding of the mechanisms controlling the differentiation of RGCs, guidance of their axons from the retina to the primary visual centers, and the refinement processes essential for the establishment of topographic maps and eye-specific axon segregation. Human disorders, such as albinism and achiasmia, that impair RGC axon growth and guidance and, thus, the establishment of a fully functioning visual system will also be discussed.

Discourse on corruption counteraction in network trade

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Leonid A. Zhigun

2015-12-01

Full Text Available Objective to determine the specific forms of corruption and promising methods to counteract corruption in network trade. Methods the combination of inductive observations comparisons generalizations facts and trends of corruption in network trade with a logical analytical deduction of economic theories and the corruption concept are the basis of the study and provide an opportunity on the one hand to assess the level of compliance of theoretical concepts of corruption with the practice and on the other handnbsp to determine their applicability to organize opposition and create conditions to prevent its occurrence to summarize the features of corruption in the form of a kickback the discourse method was applied in this work. Results on the basis of theoretical provisions and facts of corruption in trade it is proved that it has typical characteristics of corruption in commercial and nonprofit organizations. The key reasons are identified why corruption occurs in trade. Among them supply of poor quality goods at inflated prices leading to bribery in the form of laquopersonal bonusraquo to administrator of the trading organization when selling goods by an unscrupulous supplier and also supply goods to the trade organizations which will not buy without kickback. Most of these corrupt deals are carried out by natural monopolies in the form of state and municipal procurement. In some cases the kickback is the argument stimulating the decision to introduce new and advanced technologies. The factors that lead to corruption in trade are listed and reasonable methods to counteract it are grounded allowing to create conditions for its eradication in other branches of business as well. Scientific novelty for the first time a generalization has been made about the deficit as the driving force in the mechanism when the bribegivers and bribetakers change places. Practical significance the main provisions and conclusions of the article can be used in the

Benign familial fleck retina: multimodal imaging including optical coherence tomography angiography.

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Garcia, Jose Mauricio Botto de Barros; Isaac, David Leonardo Cruvinel; Sardeiro, Tainara; Aquino, Érika; Avila, Marcos

2017-01-01

This report presents multimodal imaging of a 27-year-old woman diagnosed with benign familial fleck retina (OMIM 228980), an uncommon disorder. Fundus photographs revealed retinal flecks that affected her post-equatorial retina but spared the macular area. Fundus autofluorescence and infrared imaging demonstrated a symmetrical pattern of yellow-white fleck lesions that affected both eyes. Her full-field electroretinogram and electrooculogram were normal. An optical coherence tomography B-scan was performed for both eyes, revealing increased thickness of the retinal pigmented epithelium leading to multiple small pigmented epithelium detachments. The outer retina remained intact in both eyes. Spectral-domain optical coherence tomography angiography with split-spectrum amplitude decorrelation algorithm and 3 × 3 mm structural en face optical coherence tomography did not show macular lesions. Benign familial fleck retina belongs to a heterogenous group of so-called flecked retina syndromes, and should be considered in patients with yellowish-white retinal lesions without involvement of the macula.

Benign familial fleck retina: multimodal imaging including optical coherence tomography angiography

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Jose Mauricio Botto de Barros Garcia

Full Text Available ABSTRACT This report presents multimodal imaging of a 27-year-old woman diagnosed with benign familial fleck retina (OMIM 228980, an uncommon disorder. Fundus photographs revealed retinal flecks that affected her post-equatorial retina but spared the macular area. Fundus autofluorescence and infrared imaging demonstrated a symmetrical pattern of yellow-white fleck lesions that affected both eyes. Her full-field electroretinogram and electrooculogram were normal. An optical coherence tomography B-scan was performed for both eyes, revealing increased thickness of the retinal pigmented epithelium leading to multiple small pigmented epithelium detachments. The outer retina remained intact in both eyes. Spectral-domain optical coherence tomography angiography with split-spectrum amplitude decorrelation algorithm and 3 × 3 mm structural en face optical coherence tomography did not show macular lesions. Benign familial fleck retina belongs to a heterogenous group of so-called flecked retina syndromes, and should be considered in patients with yellowish-white retinal lesions without involvement of the macula.

Monte Carlo simulation of zinc protoporphyrin fluorescence in the retina

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Chen, Xiaoyan; Lane, Stephen

2010-02-01

We have used Monte Carlo simulation of autofluorescence in the retina to determine that noninvasive detection of nutritional iron deficiency is possible. Nutritional iron deficiency (which leads to iron deficiency anemia) affects more than 2 billion people worldwide, and there is an urgent need for a simple, noninvasive diagnostic test. Zinc protoporphyrin (ZPP) is a fluorescent compound that accumulates in red blood cells and is used as a biomarker for nutritional iron deficiency. We developed a computational model of the eye, using parameters that were identified either by literature search, or by direct experimental measurement to test the possibility of detecting ZPP non-invasively in retina. By incorporating fluorescence into Steven Jacques' original code for multi-layered tissue, we performed Monte Carlo simulation of fluorescence in the retina and determined that if the beam is not focused on a blood vessel in a neural retina layer or if part of light is hitting the vessel, ZPP fluorescence will be 10-200 times higher than background lipofuscin fluorescence coming from the retinal pigment epithelium (RPE) layer directly below. In addition we found that if the light can be focused entirely onto a blood vessel in the neural retina layer, the fluorescence signal comes only from ZPP. The fluorescence from layers below in this second situation does not contribute to the signal. Therefore, the possibility that a device could potentially be built and detect ZPP fluorescence in retina looks very promising.

Genetics of lattice degeneration of the retina.

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Murakami, F; Ohba, N

1982-01-01

First-degree relatives of proband patients with lattice degeneration of the retina revealed a significantly higher prevalence of the disease than the prevalence in the general population: the former had the disease about three times as frequently as the latter. The observed data were analyzed in terms of their accordance with recognized genetic models. The inheritance pattern did not fit well to a monogenic mode of inheritance, and it was hypothesized that a polygenic or multifactorial mode of inheritance is the most likely for lattice degeneration of the retina.

Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

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Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

2017-07-01

Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

Damage and functional recovery of the mouse retina after exposure to genotoxic agents

International Nuclear Information System (INIS)

Vinogradova, Yu.V.; Tronov, V.A.; Lyakhova, K.N.; Ostrovskij, M.A.

2013-01-01

As is known, the mature retina is characterized by high radiation resistance. We showed earlier that ionizing radiation at a dose of ≥25 Gy and the chemical genotoxic agent methylnitrosourea (MNU) in a concentration of ≥60 mg/kg induce acute retinal degeneration, combined with proapoptotic protein expression. The process has a high genotoxic threshold, below which no degeneration signs were traced. The aim of this work was to study the damaging effect of ionizing radiation and MNU on the functional activity of the retina and its ability to recover after exposure to these genotoxicants. The functional activity of the mouse retina was evaluated with electroretinograms (ERG). In parallel, morphological changes in the retina were controlled, and the TUNEL detection of the death of its cell elements was performed. It has been shown that gamma rays or accelerated proton irradiation below 15 Gy cause no structural or functional changes in the mouse retina, which confirms the mature retina's high radiation resistance. Irradiation with a higher dose of 25 Gy leads to photoreceptor layer destruction. This goes along with an increase in the number of the TUNEL-positive photoreceptors, among which are cells with fragmented nuclei, which are typical of apoptosis. MNU in a concentration of 70 mg/kg caused the irreversible loss of the retina's physiological activity, and the morphological degeneration of photoreceptors and their mass death. In a concentration of 35 mg/kg, however, MNU had no cytotoxic effect on the retina. Moreover, this dose caused a reversible ERG amplitude decrease. Also, adaptive response was observed in the retina, which became apparent after two consecutive MNU injections - first, at a dose of 17 mg/kg; then, at a cytotoxic dose of 70 mg/kg. These results point to the possibility of the neurohormesis effect, which was described concerning the retina's exposure to ionizing radiation and some chemicals.

Distribution of tubulin, kinesin, and dynein in light- and dark-adapted octopus retinas.

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Martinez, J M; Elfarissi, H; De Velasco, B; Ochoa, G H; Miller, A M; Clark, Y M; Matsumoto, B; Robles, L J

2000-01-01

Cephalopod retinas exhibit several responses to light and dark adaptation, including rhabdom size changes, photopigment movements, and pigment granule migration. Light- and dark-directed rearrangements of microfilament and microtubule cytoskeletal transport pathways could drive these changes. Recently, we localized actin-binding proteins in light-/dark-adapted octopus rhabdoms and suggested that actin cytoskeletal rearrangements bring about the formation and degradation of rhabdomere microvilli subsets. To determine if the microtubule cytoskeleton and associated motor proteins control the other light/dark changes, we used immunoblotting and immunocytochemical procedures to map the distribution of tubulin, kinesin, and dynein in dorsal and ventral halves of light- and dark-adapted octopus retinas. Immunoblots detected alpha- and beta-tubulin, dynein intermediate chain, and kinesin heavy chain in extracts of whole retinas. Epifluorescence and confocal microscopy showed that the tubulin proteins were distributed throughout the retina with more immunoreactivity in retinas exposed to light. Kinesin localization was heavy in the pigment layer of light- and dark-adapted ventral retinas but was less prominent in the dorsal region. Dynein distribution also varied in dorsal and ventral retinas with more immunoreactivity in light- and dark-adapted ventral retinas and confocal microscopy emphasized the granular nature of this labeling. We suggest that light may regulate the distribution of microtubule cytoskeletal proteins in the octopus retina and that position, dorsal versus ventral, also influences the distribution of motor proteins. The microtubule cytoskeleton is most likely involved in pigment granule migration in the light and dark and with the movement of transport vesicles from the photoreceptor inner segments to the rhabdoms.

Clonal origins of cells in the pigmented retina of the zebrafish eye

International Nuclear Information System (INIS)

Streisinger, G.; Coale, F.; Taggart, C.; Walker, C.; Grunwald, D.J.

1989-01-01

Mosaic analysis has been used to study the clonal basis of the development of the pigmented retina of the zebrafish, Brachydanio rerio. Zebrafish embryos heterozygous for a recessive mutation at the gol-1 locus were exposed to gamma-irradiation at various developmental stages to create mosaic individuals consisting of wild-type pigmented cells and a clone of pigmentless (golden) cells in the eye. The contribution of individual embryonic cells to the pigmented retina was measured and the total number of cells in the embryo that contributed descendants to this tissue was determined. Until the 32-cell stage, almost every blastomere has some descendants that participate in the formation of the pigmented retina of the zebrafish. During subsequent cell divisions, up to the several thousand-cell stage, the number of ancestral cells is constant: approximately 40 cells are present that will give rise to progeny in the pigmented retina. Analysis of the size of clones in the pigmented retina indicates that the cells of this tissue do not arise through a rigid series of cell divisions originating in the early embryo. The findings that each cleavage stage cell contributes to the pigmented retina and yet the contribution of such cells is highly variable are consistent with the interpretation that clonal descendants of different blastomeres normally intermix extensively prior to formation of the pigmented retina

[Lattice degeneration of the peripheral retina: ultrastructural study].

Science.gov (United States)

Bec, P; Malecaze, F; Arne, J L; Mathis, A

1985-01-01

The ultrastructural study of a case of snail track degeneration shows the presence of lipid inclusions in both the glial and the macrophage cells in every layer of the retina, and the existence of intraretinal fibers different from collagen fibers appearing to be glial filaments similar to those found in astrocytic gliomes and to the Rosenthal fibers observed in senile nervous cells. Other features were thinning of the retina and absence of blood vessels in the retina. There are no abnormalities of the vitreo-retinal juncture. All the lesions are in agreement with those observed by Daicker [Ophthalmologica, Basel 165: 360-365, 1972; Klin. Mbl. Augenheilk. 172: 581-583, 1978] with some differences, however. They are different from those found in lattice degeneration. They show that snail track degeneration is a specific form of peripheral retinal degeneration which is quite different from lattice degeneration and must not be considered similar.

Impact of MCT1 Haploinsufficiency on the Mouse Retina

KAUST Repository

Peachey, Neal S.

2018-05-02

The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

Impact of MCT1 Haploinsufficiency on the Mouse Retina

KAUST Repository

Peachey, Neal S.; Yu, Minzhong; Han, John Y. S.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Philp, Nancy J.

2018-01-01

The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

Impact of bronchopulmonary dysplasia on brain and retina

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Annie Wing Hoi Poon

2016-04-01

Full Text Available Many premature newborns develop bronchopulmonary dysplasia (BPD, a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, ‘BPD’ group or room air (21% O2, ‘control’ group from postnatal day 4–14 (P4–14; the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P<0.0001. This increase was associated with a decrease in some brain structures [especially the whole-brain surface (P=0.02], as well as a decrease in the thickness of the retinal layers [especially the total retina (P=0.0008], compared to the room air control group. In addition, a significant negative relationship was observed between the lung structures and the brain (r=−0.49, P=0.02 and retina (r=−0.70, P=0.0008 structures. In conclusion, hyperoxia exposure impaired lung, brain, and retina structures. More severe lung injuries correlated with more severe brain and retinal injuries. This result suggests that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.

Spontaneous activity in the developing mammalian retina: Form and function

Science.gov (United States)

Butts, Daniel Allison

Spontaneous neuronal activity is present in the immature mammalian retina during the initial stages of visual system development, before the retina is responsive to light. This activity consists of bursts of action potentials fired by retinal ganglion cells, and propagates in a wavelike manner across the inner plexiform layer of the retina. Unlike waves in other neural systems, retinal waves have large variability in both their rate and direction of propagation, and individual waves only propagate across small regions of the retina. The unique properties of retinal activity arise from dynamic processes within the developing retina, and produce characteristic spatiotemporal properties. These spatiotemporal properties are of particular interest, since they are believed to play a role in visual system development. This dissertation addresses the complex spatiotemporal patterning of the retinal waves from two different perspectives. First, it proposes how the immature circuitry of the developing retina generates these patterns of activity. In order to reproduce the distinct spatiotemporal properties observed in experiments, a model of the immature retinal circuitry must meet certain requirements, which are satisfied by a coarse-grained model of the developing retina that we propose. Second, this dissertation addresses how the particular spatiotemporal patterning of the retinal waves provides information to the rest of the visual system and, as a result, can be used to guide visual system development. By measuring the properties of this information, we place constraints on the developmental mechanisms that use this activity, and show how the particular spatiotemporal properties of the retinal waves provide this information. Together, this dissertation demonstrates how the apparent complexity of retinal wave patterning can be understood both through the immature circuitry that generates it, and through the developmental mechanisms that may use it. The first three

Müller glia provide essential tensile strength to the developing retina

Science.gov (United States)

MacDonald, Ryan B.; Randlett, Owen; Oswald, Julia; Yoshimatsu, Takeshi

2015-01-01

To investigate the cellular basis of tissue integrity in a vertebrate central nervous system (CNS) tissue, we eliminated Müller glial cells (MG) from the zebrafish retina. For well over a century, glial cells have been ascribed a mechanical role in the support of neural tissues, yet this idea has not been specifically tested in vivo. We report here that retinas devoid of MG rip apart, a defect known as retinoschisis. Using atomic force microscopy, we show that retinas without MG have decreased resistance to tensile stress and are softer than controls. Laser ablation of MG processes showed that these cells are under tension in the tissue. Thus, we propose that MG act like springs that hold the neural retina together, finally confirming an active mechanical role of glial cells in the CNS. PMID:26416961

Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

Directory of Open Access Journals (Sweden)

ROBERTO PAES-DE-CARVALHO

2002-09-01

Full Text Available The nucleoside adenosine plays an important role as a neurotransmitter or neuromodulator in the central nervous system, including the retina. In the present paper we review compelling evidence showing that adenosine is a signaling molecule in the developing retina. In the chick retina, adenosine transporters are present since early stages of development before the appearance of adenosine A1 receptors modulating dopamine-dependent adenylate cyclase activity or A2 receptors that directly activate the enzyme. Experiments using retinal cell cultures revealed that adenosine is taken up by specific cell populations that when stimulated by depolarization or neurotransmitters such as dopamine or glutamate, release the nucleoside through calcium-dependent transporter-mediated mechanisms. The presence of adenosine in the extracellular medium and the long-term activation of adenosine receptors is able to regulate the survival of retinal neurons and blocks glutamate excitoxicity. Thus, adenosine besides working as a neurotransmitter or neuromodulator in the mature retina, is considered as an important signaling molecule during retinal development having important functions such as regulation of neuronal survival and differentiation.O nucleosídeo adenosina apresenta um importante papel como neurotransmissor ou neuromodulador no sistema nervoso central, inclusive na retina. Neste artigo apresentamos uma revisão das evidências que mostram que a adenosina é uma molécula sinalizadora na retina em desenvolvimento. Na retina de pinto, transportadores de adenosina estão presentes desde estágios precoces do desenvolvimento, antes do aparecimento dos receptores A1 que modulam a atividade adenilato ciclase dependente de dopamina ou dos receptores A2 que ativam diretamente a enzima. Experimentos usando culturas de células de retina revelaram que a adenosina é captada por populações celulares específicas que, quando estimuladas por despolarização ou por

Forms of the criminal environment counteraction to performing the function of state protection of participants in criminal proceedings and measures of its neutralization

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Dubonosov E.S.

2014-12-01

Full Text Available Criminal environment’s counteraction is considered as purposeful, active and intentional influence of its representatives on participants in criminal proceedings. It is directed at persons who, due to their professional duties, are involved in detection and investigation of crimes as well as court proceedings, or who possess evidentiary information (witnesses, victims, etc.. Counteraction may be expressed in different ways: discrediting operatives, investigators and judges; pressure on persons involved in the investigation and the trial through bribery, blackmail, threats to life and health of themselves and their family, etc. The administration of justice becomes inefficient due to the variety of forms and purposes of counteraction. The importance of operational units’ awareness of the activities of criminal environment representatives is shown. The importance of revealing the facts of unlawful influence on witnesses and victims of crime, who subsequently acquire procedural status of witnesses and victims, in order to prevent such facts is also stressed. It is proposed to suppress the counteraction of criminal environment by following ways: 1 identifying (with the help of informants and by crime detection actions the persons attempting to influence the preliminary investigation; 2 documenting the suspects actions aimed at illegal influence on participants in criminal proceedings for the purpose of conducting the procedural actions and decision making; 3 “in cell” (using an agent crime detection actions against detainees and arrestees throughout the whole process of covert operation; 4 creating investigative team to develop a common mechanism to neutralize criminal environment’s counteraction to crime investigation.

Identification of endogenous flurophores in the layered retina

Science.gov (United States)

Xu, Gaixia; Chen, Danni; Sun, Yiwen; Qu, Junle; Lin, Ziyang; Ding, Zhihua; Niu, Hanben

2007-05-01

In this paper, we measured and analyzed the characteristic of endogenous fluorophores in porcine layered retina by using advanced fluorescence spectroscopy and microscopy imaging technology. It was found that there were obvious contrasts corresponding to the different layers of retina, which may be important for fundus disease diagnosis. The retinal pigment epithelium cells exhibited strong autofluorescence with as emission peak of 600+/-10nm when excited with 860-nm light. The emission peak of photoreceptors was at 652+/-5nm, and the emission peak of retinal vessels layer was weak and at 640~700nm, when excited with 488-nm light. Autofluorescence images of three layers of retina were obtained using the same setup. We concluded that the main endogenous fluorophore in PRE was lipofuscin and that in retinal vessels was porphyrin. What's more, the FMHW (full width at half. maximum) of retinal fluorescence spectrum was broad, which suggested that there wasn't only one endogenous fluorophores of tissues excited.

Standard anatomical and visual space for the mouse retina: computational reconstruction and transformation of flattened retinae with the Retistruct package.

Directory of Open Access Journals (Sweden)

David C Sterratt

Full Text Available The concept of topographic mapping is central to the understanding of the visual system at many levels, from the developmental to the computational. It is important to be able to relate different coordinate systems, e.g. maps of the visual field and maps of the retina. Retinal maps are frequently based on flat-mount preparations. These use dissection and relaxing cuts to render the quasi-spherical retina into a 2D preparation. The variable nature of relaxing cuts and associated tears limits quantitative cross-animal comparisons. We present an algorithm, "Retistruct," that reconstructs retinal flat-mounts by mapping them into a standard, spherical retinal space. This is achieved by: stitching the marked-up cuts of the flat-mount outline; dividing the stitched outline into a mesh whose vertices then are mapped onto a curtailed sphere; and finally moving the vertices so as to minimise a physically-inspired deformation energy function. Our validation studies indicate that the algorithm can estimate the position of a point on the intact adult retina to within 8° of arc (3.6% of nasotemporal axis. The coordinates in reconstructed retinae can be transformed to visuotopic coordinates. Retistruct is used to investigate the organisation of the adult mouse visual system. We orient the retina relative to the nictitating membrane and compare this to eye muscle insertions. To align the retinotopic and visuotopic coordinate systems in the mouse, we utilised the geometry of binocular vision. In standard retinal space, the composite decussation line for the uncrossed retinal projection is located 64° away from the retinal pole. Projecting anatomically defined uncrossed retinal projections into visual space gives binocular congruence if the optical axis of the mouse eye is oriented at 64° azimuth and 22° elevation, in concordance with previous results. Moreover, using these coordinates, the dorsoventral boundary for S-opsin expressing cones closely matches

Localization and Developmental Expression Patterns of CSPG in the RCS Rat Retina

Directory of Open Access Journals (Sweden)

Li-Feng Chen

2011-05-01

Full Text Available Purpose: Investigate changes in chondroitin sulfate proteoglycan (CSPG distribution in Royal College of Surgeons (RCS rat retinae. Could CSPGs distribution act as a physical barrier to transplanted cell migration in degenerating retinae? Methods: CSPG expression was examined in RCS and Long-Evans rat retinae from birth to postnatal day 150 (PND150 using immunofluorescence and western-blots. Results: Both groups showed a rapid rise in CSPG expression on PND14, which peaked on PND21 before declining to lower levels by PND35. CSPG expression had risen again by PND90 and remained elevated for the duration of the study (PND150. However, from PND21, CSPG expression was significantly higher (p ≤ 0.05, n = 5 in Long-Evans rat retinae. CSPG-positive cells were localized in the ganglion cell layer (GCL and the photoreceptor outer segment debris zone (DZ; CSPG expression in the DZ was the main contributor to the higher expression in older animals for both groups. Conclusions: Increased expression of CSPGs in the DZ may act as a physical barrier following retinal cellular transplantation. CSPGs in the GCL is probably related to dendritic changes. CSPG accumulation in the older retinae suggests that aging influences the microenvironment in the retina, which may affect the efficacy of cell transplantation.

Sialyltransferase activity probably counteracts that of sialidase as ...

African Journals Online (AJOL)

Sialyltransferase activity probably counteracts that of sialidase as one of the possible mechanisms of natural recovery or stabilization of erythrocyte mass in trypanosome-infected animals - A perspective.

Bcl-2 expression during the development and degeneration of RCS rat retinae.

Science.gov (United States)

Sharma, R K

2001-12-14

In various hereditary retinal degenerations, including that in Royal College of Surgeons (RCS) rats, the photoreceptors ultimately die by apoptosis. Bcl-2 is one of the genes, which regulates apoptosis and is thought to promote survival of cells. This study has investigated the developmental expression of Bcl-2 in RCS rat, which is a well-studied animal model for hereditary retinal degeneration. An antibody against Bcl-2 was used for its immunohistochemical localization in dystrophic RCS rat retinae from postnatal (PN) days 4, 7, 13, 35, 45, 70, 202 and 14 months. Results were compared with Bcl-2 localization in congenic non-dystrophic rats from PN 4, 7, 13, 44, 202 and 14 months. Bcl-2 immunoreactivity in non-dystrophic retinae was already present in PN 4 retinae in the nerve fiber layer (presumably in the endfeet of immature Müller cells) and in the proximal parts of certain radially aligned neuroepithelial cells/immature Müller cell radial processes. With increasing age the immunoreactivity in relatively more mature Müller cell radial processes spread distally towards the outer retina and between PN 13 and 44 it reached the adult distribution. No cell bodies in the ganglion cell layer were found to be immunoreactive. Expression of Bcl-2 immunoreactivity in dystrophic RCS rat retinae closely resembled that of non-dystrophic retinae. No immunoreactivity was seen in photoreceptors or retinal pigment epithelium in dystrophic or non-dystrophic retinae. In conclusion, Bcl-2 expression is not altered, either in terms of its chronology or the cell type expressing it, during retinal degeneration in RCS rats.

Progranulin regulates neurogenesis in the developing vertebrate retina.

Science.gov (United States)

Walsh, Caroline E; Hitchcock, Peter F

2017-09-01

We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed-retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 77: 1114-1129, 2017. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.

Protein changes in the retina following experimental retinal detachment in rabbits

DEFF Research Database (Denmark)

Mandal, Nakul; Lewis, Geoffrey P.; Fisher, Steven K.

2011-01-01

Retinal detachment leads to the widespread cellular remodeling of the retina. The purpose of this study was to identify protein changes that accompany these cellular alterations by comparing the proteomic profiles of sham and experimentally detached rabbit retina. Elucidation of the proteins most...

Genetic and immunohistochemical analysis of HSPA5 in mouse and human retinas.

Science.gov (United States)

Chintalapudi, Sumana R; Wang, XiaoFei; Li, Huiling; Lau, Yin H Chan; Williams, Robert W; Jablonski, Monica M

2016-01-01

Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina. Quantitative trait locus (QTL) mapping was used to map the genomic region that regulates Hspa5 in the cross between C57BL/6J X DBA/2J mice (BXD) genetic reference panel. The stepwise refinement of candidate genes was based on expression QTL mapping, gene expression correlation analyses (direct and partial), and analysis of regional sequence variants. The subcellular localization of candidate proteins and HSPA5 in mouse and human retinas was evaluated by immunohistochemistry. Differences in the localization of extracellular HSPA5 were assessed between healthy human donor and atrophic age-related macular degeneration (AMD) donor eyes. In the eyes of healthy mice, extracellular HSPA5 was confined to the area around the cone photoreceptor outer segments. Mapping variation in Hspa5 mRNA expression levels in the retina revealed a statistically significant trans -acting expression QTL (eQTL) on Chromosome 2 (Chr 2) and a suggestive locus on Chr 15. Sulf2 on Chr 2 was the strongest candidate gene based on partial correlation analysis, Pearson correlation with Hspa5 , expression levels in the retina, a missense variant in exon 14, and its reported function in the extracellular matrix and interphotoreceptor matrix. SULF2 is localized to the rod and cone photoreceptors in both human and mouse retinas. In human retinas with no pathology, extracellular HSPA5 was localized around many cones within the macular area. In contrast, fewer HSPA5-immunopositive cones were

EVALUATION OF INHOMOGENEITIES IN HISTOLOGICAL STRUCTURES (CARTILAGE, RETINA

Directory of Open Access Journals (Sweden)

Lutz Muche

2011-05-01

Full Text Available This paper investigates histological tissues by means of image analysis and spatial statistics. For the quantification of cell frequencies and accumulations two statistical characteristics, intensity function and cluster density, are suggested. The samples are histological sections of human articular cartilage and human retina considered in view of changes during the ageing process. The articular cartilage is characterized by continuous changes of both functions, the cell intensity as well as the clusterization. In contrast, the retina is a trilaminar structure formed in the early embryonic stage without changes by ageing.

Pannexin1 in the outer retina of the zebrafish, Danio rerio

NARCIS (Netherlands)

Prochnow, N.; Hoffmann, S.; Vroman, R.; Klooster, J.; Bunse, S.; Kamermans, M.; Dermietzel, R.; Zoidl, G.

2009-01-01

In the retina, chemical and electrical synapses couple neurons into functional networks. New candidates encoding for electrical synapse proteins have recently emerged. In the present study, we determined the localization of the candidate protein pannexin1 (zfPanx1) in the zebrafish retina and

Optic nerve signals in a neuromorphic chip I: Outer and inner retina models.

Science.gov (United States)

Zaghloul, Kareem A; Boahen, Kwabena

2004-04-01

We present a novel model for the mammalian retina and analyze its behavior. Our outer retina model performs bandpass spatiotemporal filtering. It is comprised of two reciprocally connected resistive grids that model the cone and horizontal cell syncytia. We show analytically that its sensitivity is proportional to the space-constant-ratio of the two grids while its half-max response is set by the local average intensity. Thus, this outer retina model realizes luminance adaptation. Our inner retina model performs high-pass temporal filtering. It features slow negative feedback whose strength is modulated by a locally computed measure of temporal contrast, modeling two kinds of amacrine cells, one narrow-field, the other wide-field. We show analytically that, when the input is spectrally pure, the corner-frequency tracks the input frequency. But when the input is broadband, the corner frequency is proportional to contrast. Thus, this inner retina model realizes temporal frequency adaptation as well as contrast gain control. We present CMOS circuit designs for our retina model in this paper as well. Experimental measurements from the fabricated chip, and validation of our analytical results, are presented in the companion paper [Zaghloul and Boahen (2004)].

Thyroid Hormone Signaling in the Mouse Retina.

Directory of Open Access Journals (Sweden)

Patrick Arbogast

Full Text Available Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express β-galactosidase (β-gal under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3 and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells showed strong β-gal labeling. In the inner nuclear layer (INL, a minority of glycineric and GABAergic amacrine cells showed β-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, β-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic 'starburst' amacrines. At postnatal day 10, there also was a high density of strongly β-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no β-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of β-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.

Modeling and Simulation of Microelectrode-Retina Interactions

Energy Technology Data Exchange (ETDEWEB)

Beckerman, M

2002-11-30

The goal of the retinal prosthesis project is the development of an implantable microelectrode array that can be used to supply visually-driven electrical input to cells in the retina, bypassing nonfunctional rod and cone cells, thereby restoring vision to blind individuals. This goal will be achieved through the study of the fundamentals of electrical engineering, vision research, and biomedical engineering with the aim of acquiring the knowledge needed to engineer a high-density microelectrode-tissue hybrid sensor that will restore vision to millions of blind persons. The modeling and simulation task within this project is intended to address the question how best to stimulate, and communicate with, cells in the retina using implanted microelectrodes.

Cyber terrorism prevention and counteraction workshop review

NARCIS (Netherlands)

Pastukhov, O.M.

2011-01-01

A NATO Advanced Training Course (ATC ) on Cyber Terrorism Prevention and Counteraction workshop, held in Kiev on September 27-29, 2010, allowed the participants to share their experiences with experts from Ukraine, a Partnership for Peace country. The participants exchanged their ideas on the ways

Direct transdifferentiation in the vertebrate retina.

Science.gov (United States)

Opas, M; Dziak, E

1998-03-01

Transdifferentiation is the process by which differentiated cells alter their identity to become other, distinct cell types. The conversion of neural retina into lens epithelium is one of the most spectacular examples of transdifferentiation. We show that the redirection of cell fate from neural retina to lens and subsequent transdifferentiation is independent of cell replication as it occurs in growth-arrested cell populations. Using DNA ratiometry of individual cells in these cultures we show that, indeed, individual amitotic cells do transdifferentiate. Hence, choice of fate in transdifferentiating cells does not rely on a "community effect" but instead can be categorized as a leadership effect> For lack of overt lens progenitors, and most importantly, for its mitotic independence, we conclude that lens colony formation in vitro does occur by direct transdifferentiation and not by clonal proliferation of progenitor cells.

Distribution of photon absorption rates across the rat retina.

Science.gov (United States)

Williams, T P; Webbers, J P; Giordano, L; Henderson, R P

1998-04-15

1. An investigation into the distribution of light intensity across the rat retina was carried out on excised, intact rat eyes exposed to Ganzfeld illumination from a helium-neon laser (543 nm). 2. Some of the light entering the eyes exits through the sclera where its intensity can be monitored with an optical 'pick-up' that samples the intensity coming from a small region of external sclera and underlying retina. The spatial resolution of the pick-up is such that it samples light that has passed through ca 2 % of the rods in the rat eye. 3. Some of the laser light is absorbed by the rod pigment, rhodopsin, which gradually bleaches. Bleaching in the retina, in turn, causes an exponential increase in intensity emanating from the sclera. By monitoring this intensity increase, we are able to measure two important parameters in a single bleaching run: the local rhodopsin concentration and the local intensity falling on the rods. 4. With an ocular transmission photometer, we have measured both the local intensity and the local rhodopsin concentration across wide regions of rat retina. Both pigmented and albino rats were studied. 5. The distributions of rhodopsin and intensity were both nearly uniform; consequently, the product, (rhodopsin concentration) x (intensity), was similarly nearly equal across the retina. This means that the initial rate of photon absorption is about the same at all retinal locations. 6. Interpreted in terms of photostasis (the regulation of daily photon catch), this means that the rate of photon absorption is about the same in each rod, viz. 14 400 photons absorbed per rod per second. Since this rate of absorption is sufficient to saturate the rod, one possible purpose of photostasis is to maintain the rod system in a saturated state during daylight hours.

Genetic and immunohistochemical analysis of HSPA5 in mouse and human retinas

Science.gov (United States)

Chintalapudi, Sumana R.; Wang, XiaoFei; Li, Huiling; Lau, Yin H. Chan; Williams, Robert W.; Jablonski, Monica M.

2016-01-01

Purpose Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina. Methods Quantitative trait locus (QTL) mapping was used to map the genomic region that regulates Hspa5 in the cross between C57BL/6J X DBA/2J mice (BXD) genetic reference panel. The stepwise refinement of candidate genes was based on expression QTL mapping, gene expression correlation analyses (direct and partial), and analysis of regional sequence variants. The subcellular localization of candidate proteins and HSPA5 in mouse and human retinas was evaluated by immunohistochemistry. Differences in the localization of extracellular HSPA5 were assessed between healthy human donor and atrophic age-related macular degeneration (AMD) donor eyes. Results In the eyes of healthy mice, extracellular HSPA5 was confined to the area around the cone photoreceptor outer segments. Mapping variation in Hspa5 mRNA expression levels in the retina revealed a statistically significant trans-acting expression QTL (eQTL) on Chromosome 2 (Chr 2) and a suggestive locus on Chr 15. Sulf2 on Chr 2 was the strongest candidate gene based on partial correlation analysis, Pearson correlation with Hspa5, expression levels in the retina, a missense variant in exon 14, and its reported function in the extracellular matrix and interphotoreceptor matrix. SULF2 is localized to the rod and cone photoreceptors in both human and mouse retinas. In human retinas with no pathology, extracellular HSPA5 was localized around many cones within the macular area. In contrast, fewer HSPA5

Alanine Counteracts the Destabilizing Effect that Urea has on RNase-A.

Science.gov (United States)

Chowhan, Rimpy K; Ali, Fasil; Bhat, Mohd Y; Rahman, Safikur; Singh, Laishram R; Ahmad, Faizan; Dar, Tanveer A

2016-01-01

It is generally believed that organisms use and accumulate methylamine osmolytes to prevent urea's damaging effect on protein stability and activity. However, urea-rich cells not only accumulate methylamines but also many other methylated and non-methylated compounds as well. But, so far it is not known whether osmolytes that are not accumulated in urea-rich cells could also confer urea-counteracting properties. We investigated the behavior of a non-methylamine osmolyte, alanine for its counteracting effect against urea denaturation of a model protein, ribonuclease A (RNase-A). We have measured structure and thermodynamic parameters (Tm, ΔHm, and ΔGD°) of RNase-A in the presence of alanine, urea and their combination. The results were also compared with the ability of glycine (osmolyte lacking one methyl group when compared with alanine) to counter urea's effect on protein stability. We observed that alanine but not glycine counteracts urea's harmful effect on RNase-A stability. The results indicated that alanine (in addition to methylamine osmolytes) may serve as an alternate urea-counteractant. Since glycine fails to protect RNase-A from urea's destabilizing effect, it seems that methylation to glycine might have some evolutionary significance to protect proteins against harmful effects of urea.

Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys.

Science.gov (United States)

Johnson, Elizabeth J; Neuringer, Martha; Russell, Robert M; Schalch, Wolfgang; Snodderly, D Max

2005-02-01

Macular pigment (MP) is composed of the xanthophylls lutein (L) and zeaxanthin (Z) and may help to prevent age-related macular degeneration or retard its progression. In this study the effects of L or Z supplementation on carotenoid levels was examined in serum, adipose tissue, and retina in rhesus monkeys with no previous intake of xanthophylls. From birth to 7 to 16 years of age, 18 rhesus monkeys were fed semipurified diets containing all essential nutrients but no xanthophylls. Six were supplemented with pure L and 6 with pure Z at 3.9 micromol/kg per day for 24 to 101 weeks. At baseline and at 4- to 12-week intervals, carotenoids in adipose tissue were measured by HPLC. At study completion, carotenoids in serum and retina (central 4 mm, 8-mm annulus, and the periphery) were determined. Results were compared with data from control monkeys fed a standard laboratory diet. Monkeys fed xanthophyll-free diets had no L or Z in serum or tissues. After L or Z supplementation, serum and adipose tissue concentrations significantly increased in the supplemented groups. Both L and 3R,3'S-Z (RSZ or meso-Z, not present in the diet) were incorporated into retinas of monkeys supplemented with L, with RSZ present only in the macula (central 4 mm). All-trans Z, but no RSZ, accumulated in retinas of monkeys supplemented with Z. L is the precursor of RSZ, a major component of macular pigment. Xanthophyll-free monkeys can accumulate retinal xanthophylls and provide a valuable model for examining their uptake and conversion.

Frequency of Toxoplasma gondii in the retina in eye banks in Brazil.

Science.gov (United States)

Costa, Deise F; Nascimento, Heloisa; Sutili, Aline; Nobrega, Fernando A J; Fowler, Flavio; Nobrega, Mario Junqueira; Garrido, Cristina; de Oliveira Dias, Janaina; Adán, Consuelo B D; Rizzo, Luiz Vicente; Silveira, Claudio; Belfort, Rubens; Commodaro, Alessandra G

2017-07-01

Ocular toxoplasmosis is the main cause of posterior uveitis worldwide frequently leading to vision loss. In Brazil, the seroprevalence of Toxoplasma gondii infection ranges from 50 to 80% depending of the region studied. The frequency of toxoplasmic retinal scar may reach 18% of the adults in the South of Brazil. Our goal was to determine the frequency of T. gondii DNA in retinas from eye banks from different regions in Brazil. A total of 162 eyes were obtained from eye banks in Manaus (n = 60), Sao Paulo (n = 60), Chapeco (n = 26), and Joinville (n = 16). The retinas were macroscopically analyzed and collected for DNA extraction. Real-time PCR (qPCR) was performed using the T. gondii B1 marker. By qPCR, a higher frequency of T. gondii DNA in the retinas from the eye bank of Joinville (25%) was found when compared to Manaus (5%). The retinas from Sao Paulo and Chapeco were qPCR negative. Clinical examination determined the retina lesions to be compatible with toxoplasmosis in the following frequencies: Joinville (62.5%), Manaus (10%), Sao Paulo (6.7%), and Chapeco (15.4%).

Some indications of structural damage in retina by heavy ion radiation

International Nuclear Information System (INIS)

Nelson, A.C.; Hayes, T.L.; Tobias, C.A.; Yang, T.C.

1981-01-01

At the Lawrence Berkeley Laboratory Bevalac Facility, iron nuclei were accelerated to an energy of 600 MeV/amu. The beam of iron thus obtained was used to irradiate living biological specimens in order to study possible microscopic tissue damage with the aid of SEM. The experiments involved total head irradiation of live rats which were subsequently returned to their cages to remain for 1 day and 30 days before further examination. After the 1 day and 30 day waits, both eyes were enucleated and placed in chemical fixative followed by ethanol dehydration and critical point drying. Retinas were carefully removed from the eye cups and loaded separately on aluminum stubs which were sputter coated. SEM of the 1 day and 30 day retinas revealed lesions which were not found at all in control retinas. The 1 day and 30 day retinas manifest regions where outer rod segments were missing or rearranged. A single energetic iron nucleus may be capable of generating a retinal lesion which becomes enlarged as biological processes intervene during the 1 day and 30 day waits. Being composed of highly specialized nerve cells, retinas cannot regenerate following irradiation which severely damages the rod cells. Thus one would expect the observed radiation induced retinal lesions to correspond to permanent tissue damage and possible loss of visual acuity in the intact animal

Counteracting 16-QAM Optical Fiber Transmission Impairments With Iterative Turbo Equalization

DEFF Research Database (Denmark)

Arlunno, Valeria; Caballero Jambrina, Antonio; Borkowski, Robert

2013-01-01

A turbo equalization (TE) scheme based on convolutional code and normalized least mean square equalizer for coherent optical communication links is proposed and experimentally demonstrated. The proposed iterative TE technique is proved effective for counteracting polarization-division-multiplexin......A turbo equalization (TE) scheme based on convolutional code and normalized least mean square equalizer for coherent optical communication links is proposed and experimentally demonstrated. The proposed iterative TE technique is proved effective for counteracting polarization...

Processes of Legislative Adaptation Undertaken by the Romanian Public Administration in the Context of the Global Economic Crisis

Directory of Open Access Journals (Sweden)

Ani Matei

2015-05-01

Full Text Available As the economic crisis is further building the administrative burden of the Romanian public administration, the legislation is constantly reshaped in order to counteract the obstacles the crisis imposes. In order to counteract the effects of the economic crisis, the Romanian public administration has undergone a series of reforms that aimed at administrative simplification, normative simplification and reducing the public expenditures. The goal of the article is to uncover and analyze the courses of action proclaimed or adopted by Romania in the light of legislative simplification. Based on relevant literature, the parameters of empiric analysis are identified and used to acknowledge the types of measures adopted. These elements of change are depicted from relevant official documents of political or juridical power. The conclusion of the article represents an assessment of the legislative measures undertaken and points out the general action plan of the Romanian public administration.

Insulin-like activity in the retina

International Nuclear Information System (INIS)

Das, A.

1986-01-01

A number of studies have recently demonstrated that insulin or a homologous peptide may be synthesized outside the pancreas also. The present study was designed to investigate whether insulin-like activity exists in the retina, and if it exists, whether it is due to local synthesis of insulin or a similar peptide in the retina. To determine whether the insulin-like immunoreactivity in retinal glial cells is due to binding and uptake or local synthesis of insulin, a combined approach of immunocytochemistry and in situ DNA-RNA hybridization techniques was used on cultured rat retinal glial cells. Insulin-like immunoreactivity was demonstrated in the cytoplasma of these cells. In situ hybridization studies using labeled rat insulin cDNA indicated that these cells contain the mRNA necessary for de novo synthesis of insulin or a closely homologous peptide. Since human retinal cells have, as yet, not been conveniently grown in culture, an ocular tumor cell line, human Y79 retinoblastoma was used as a model to extend these investigations. The presence of insulin-like immunoreactivity as well as insulin-specific mRNA was demonstrated in this cell line. Light microscopic autoradiography following incubation of isolated rat retinal cells with 125 I-insulin showed the presence of insulin binding sites on the photoreceptors and amarcine cells. On the basis of these observations that rat retina glial cells, including Muller cells are sites of synthesis of insulin or a similar peptide, a model for the pathogenesis of dabetic retinopathy is proposed

Rod photoreceptors express GPR55 in the adult vervet monkey retina

DEFF Research Database (Denmark)

Bouskila, Joseph; Javadi, Pasha; Casanova, Christian

2013-01-01

. Yet, its formal classification is still a matter of debate. CB1R and CB2R expression patterns are well described for rodent and monkey retinas. In the monkey retina, CB1R has been localized in its neural (cone photoreceptor, horizontal, bipolar, amacrine and ganglion cells) and CB2R in glial...

Functional and Cellular Responses to Laser Injury in the Rat Snake Retina

National Research Council Canada - National Science Library

Glickman, Randolph D; Elliott, III, W. R; Kumar, Neeru

2007-01-01

.... This animal is of interest for vision research because its eye has an all-cone retina. A linear array of 5 thermal lesions was placed in the retina of anesthetized animals, near the area centralis, using a Nd:VO4 laser (532 nm...

The Neural Retina in Retinopathy of Prematurity

Science.gov (United States)

Hansen, Ronald M.; Moskowitz, Anne; Akula, James D.; Fulton, Anne B.

2016-01-01

Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP. PMID:27671171

Retina-like sensor image coordinates transformation and display

Science.gov (United States)

Cao, Fengmei; Cao, Nan; Bai, Tingzhu; Song, Shengyu

2015-03-01

For a new kind of retina-like senor camera, the image acquisition, coordinates transformation and interpolation need to be realized. Both of the coordinates transformation and interpolation are computed in polar coordinate due to the sensor's particular pixels distribution. The image interpolation is based on sub-pixel interpolation and its relative weights are got in polar coordinates. The hardware platform is composed of retina-like senor camera, image grabber and PC. Combined the MIL and OpenCV library, the software program is composed in VC++ on VS 2010. Experience results show that the system can realizes the real-time image acquisition, coordinate transformation and interpolation.

A comparison of some organizational characteristics of the mouse central retina and the human macula.

Science.gov (United States)

Volland, Stefanie; Esteve-Rudd, Julian; Hoo, Juyea; Yee, Claudine; Williams, David S

2015-01-01

Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

Cold Shock Proteins Are Expressed in the Retina Following Exposure to Low Temperatures.

Directory of Open Access Journals (Sweden)

Ignacio M Larrayoz

Full Text Available Hypothermia has been proposed as a therapeutic intervention for some retinal conditions, including ischemic insults. Cold exposure elevates expression of cold-shock proteins (CSP, including RNA-binding motif protein 3 (RBM3 and cold inducible RNA-binding protein (CIRP, but their presence in mammalian retina is so far unknown. Here we show the effects of hypothermia on the expression of these CSPs in retina-derived cell lines and in the retina of newborn and adult rats. Two cell lines of retinal origin, R28 and mRPE, were exposed to 32°C for different time periods and CSP expression was measured by qRT-PCR and Western blotting. Neonatal and adult Sprague-Dawley rats were exposed to a cold environment (8°C and expression of CSPs in their retinas was studied by Western blotting, multiple inmunofluorescence, and confocal microscopy. RBM3 expression was upregulated by cold in both R28 and mRPE cells in a time-dependent fashion. On the other hand, CIRP was upregulated in R28 cells but not in mRPE. In vivo, expression of CSPs was negligible in the retina of newborn and adult rats kept at room temperature (24°C. Exposure to a cold environment elicited a strong expression of both proteins, especially in retinal pigment epithelium cells, photoreceptors, bipolar, amacrine and horizontal cells, Müller cells, and ganglion cells. In conclusion, CSP expression rapidly rises in the mammalian retina following exposure to hypothermia in a cell type-specific pattern. This observation may be at the basis of the molecular mechanism by which hypothermia exerts its therapeutic effects in the retina.

Autofluorescence from the outer retina and subretinal space: hypothesis and review.

Science.gov (United States)

Spaide, Richard

2008-01-01

To review the pathophysiologic principles underlying increased autofluorescence from the outer retina and subretinal space using selected diseases as examples. The ocular imaging information and histopathologic features, when known, were integrated for diseases causing increased autofluorescence from the outer retina and subretinal space. Inferences were taken from this information and used to create a classification scheme. These diseases are principally those that cause separation of the outer retina from the retinal pigment epithelium, thereby preventing proper phagocytosis of photoreceptor outer segments. The separation can arise from increased exudation into the subretinal space or inadequate removal of fluid from the subretinal space. Lack of normal outer segment processing initially leads to increased accumulation of outer segments on the outer retina and subretinal space. Over time, this material is visible as an increasingly thick coating on the outer retina, is yellow, and is autofluorescent. Over time, atrophy develops with thinning of the deposited material and decreasing autofluorescence. The accumulated material is ultimately capable of inducing damage to the retinal pigment epithelium. Diseases causing accumulation of the material include central serous chorioretinopathy, vitelliform macular dystrophy, acute exudative polymorphous vitelliform maculopathy, choroidal tumors, and vitreomacular traction syndrome. The physical separation of the retinal outer segments from the retinal pigment epithelium hinders proper phagocytosis of the outer segments. Accumulation of the shed but not phagocytized outer segments plays a role in disease manifestations for a number of macular diseases.

Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration

Science.gov (United States)

Haynes, Tracy; Luz-Madrigal, Agustin; Reis, Edimara S.; Echeverri Ruiz, Nancy P.; Grajales-Esquivel, Erika; Tzekou, Apostolia; Tsonis, Panagiotis A.; Lambris, John D.; Del Rio-Tsonis, Katia

2013-01-01

Identifying the initiation signals for tissue regeneration in vertebrates is one of the major challenges in regenerative biology. Much of the research thus far has indicated that certain growth factors have key roles. Here we show that complement fragment C3a is sufficient to induce complete regeneration of the embryonic chick retina from stem/progenitor cells present in the eye, independent of fibroblast growth factor receptor signaling. Instead, C3a induces retina regeneration via STAT3 activation, which in turn activates the injury- and inflammation-responsive factors, IL-6, IL-8 and TNF-α. This activation sets forth regulation of Wnt2b, Six3 and Sox2, genes associated with retina stem and progenitor cells. Thus, our results establish a mechanism for retina regeneration based on injury and inflammation signals. Furthermore, our results indicate a unique function for complement anaphylatoxins that implicate these molecules in the induction and complete regeneration of the retina, opening new avenues of experimentation in the field. PMID:23942241

Training and professional profile of retinologists in Spain: Retina 2 project, Report 4.

Science.gov (United States)

Pastor, J Carlos; Fernández, Itziar; Rojas, Jimena; Coco, Rosa; Sanabria, Maria R; Rodríguez-de la Rúa, Enrique; Sánchez, Diego; Valverde, Carmen; Sala-Puigdollers, Anna

2011-01-01

Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties. After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined. Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%). Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5%) practiced anterior segment surgery, and 78.7% declared skills in vitrectomy. We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.

Counteracting Age Stereotypes: A Self-Awareness Manipulation

Science.gov (United States)

Chen, Yiwei; Pethtel, Olivia; Ma, Xiaodong

2010-01-01

The major goals of the present study were to (a) examine age differences in susceptibility to age stereotypes and (b) test a self-awareness manipulation in counteracting age stereotypes. Young and older adults read two sets of descriptors that only differed in the to-be-ignored age-related information. In the high self-awareness condition,…

Image Signal Transfer Method in Artificial Retina using Laser

Energy Technology Data Exchange (ETDEWEB)

Yoon, I.Y.; Lee, B.H.; Kim, S.J. [Seoul National University, Seoul (Korea)

2002-05-01

Recently, the research on artificial retina for the blind is active. In this paper a new optical link method for the retinal prosthesis is proposed. Laser diode system was chosen to transfer image into the eye in this project and the new optical system was designed and evaluated. The use of laser diode array in artificial retina system makes system simple for lack of signal processing part inside of the eyeball. Designed optical system is enough to focus laser diode array on photodiode array in 20X20 application. (author). 11 refs., 7 figs., 2 tabs.

HB-EGF is necessary and sufficient for Müller glia dedifferentiation and retina regeneration

Science.gov (United States)

Wan, Jin; Ramachandran, Rajesh; Goldman, Daniel

2011-01-01

Summary Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that proHB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals. PMID:22340497

Dual cameras acquisition and display system of retina-like sensor camera and rectangular sensor camera

Science.gov (United States)

Cao, Nan; Cao, Fengmei; Lin, Yabin; Bai, Tingzhu; Song, Shengyu

2015-04-01

For a new kind of retina-like senor camera and a traditional rectangular sensor camera, dual cameras acquisition and display system need to be built. We introduce the principle and the development of retina-like senor. Image coordinates transformation and interpolation based on sub-pixel interpolation need to be realized for our retina-like sensor's special pixels distribution. The hardware platform is composed of retina-like senor camera, rectangular sensor camera, image grabber and PC. Combined the MIL and OpenCV library, the software program is composed in VC++ on VS 2010. Experience results show that the system can realizes two cameras' acquisition and display.

Frequency spectrum might act as communication code between retina and visual cortex I.

Science.gov (United States)

Yang, Xu; Gong, Bo; Lu, Jian-Wei

2015-01-01

To explore changes and possible communication relationship of local potential signals recorded simultaneously from retina and visual cortex I (V1). Fourteen C57BL/6J mice were measured with pattern electroretinogram (PERG) and pattern visually evoked potential (PVEP) and fast Fourier transform has been used to analyze the frequency components of those signals. The amplitude of PERG and PVEP was measured at about 36.7 µV and 112.5 µV respectively and the dominant frequency of PERG and PVEP, however, stay unchanged and both signals do not have second, or otherwise, harmonic generation. The results suggested that retina encodes visual information in the way of frequency spectrum and then transfers it to primary visual cortex. The primary visual cortex accepts and deciphers the input visual information coded from retina. Frequency spectrum may act as communication code between retina and V1.

Counteracting venous stasis during acute lower leg immobilization.

NARCIS (Netherlands)

Poelkens, F.; Thijssen, D.H.J.; Kersten, B.T.P.; Scheurwater, H.; Laarhoven, E.W. van; Hopman, M.T.E.

2006-01-01

AIM: During lower limb immobilization, patients are at risk to develop deep venous thrombosis. Recently, a water-pad was developed that should counteract venous stasis. The water-pad, located under the plaster, mobilizes water from the foot to the calf during weight bearing and, thereby, imitates

TOPOGRAPHIC ORGANIZATION AND SPECIALIZED AREAS IN THE RETINA OF Callopistes palluma: GANGLION CELL LAYER

OpenAIRE

Inzunza, Oscar; Barros B., Zitta; Bravo, Hermes

1998-01-01

In this paper we analyze the topographic distribution and cell body size of neurons (ganglion and displaced amacrine) of layer 8 of the retina in the chilean reptile Callopistes palluma; using whole mount retinaswith nissl stain. Callopistes palluma retina has an area centralis without fovea in which the ganglion cell density amounts 20.000 cells / µm2 while the displaced amacrine neurons is about 7.000 cells / µm2. This neural density decreased gradually towards the peripheral retina. A hor...

Frequency spectrum might act as communication code between retina and visual cortex I

Directory of Open Access Journals (Sweden)

Xu Yang

2015-12-01

Full Text Available AIM: To explore changes and possible communication relationship of local potential signals recorded simultaneously from retina and visual cortex I (V1. METHODS: Fourteen C57BL/6J mice were measured with pattern electroretinogram (PERG and pattern visually evoked potential (PVEP and fast Fourier transform has been used to analyze the frequency components of those signals. RESULTS: The amplitude of PERG and PVEP was measured at about 36.7 µV and 112.5 µV respectively and the dominant frequency of PERG and PVEP, however, stay unchanged and both signals do not have second, or otherwise, harmonic generation. CONCLUSION: The results suggested that retina encodes visual information in the way of frequency spectrum and then transfers it to primary visual cortex. The primary visual cortex accepts and deciphers the input visual information coded from retina. Frequency spectrum may act as communication code between retina and V1.

Towards photovoltaic powered artificial retina

Directory of Open Access Journals (Sweden)

Santiago Silvestre

2011-11-01

Full Text Available The aim of this article is to provide an overview of current and future concepts in the field of retinal prostheses, and is focused on the power supply based on solar energy conversion; we introduce the possibility of using PV minimodules as power supply for a new concept of retinal prostheses: Photovoltaic Powered Artificial Retina (PVAR. Main characteristics of these PV modules are presented showing its potential for this application.

Training and professional profile of retinologists in Spain: Retina 2 project, Report 4

Directory of Open Access Journals (Sweden)

Pastor JC

2011-04-01

Full Text Available J Carlos Pastor1,3, Itziar Fernández2, Jimena Rojas1, Rosa Coco1, Maria R Sanabria1, Enrique Rodríguez-de la Rúa1,3, Diego Sánchez3, Carmen Valverde3, Anna Sala Puigdollers1,31University Institute of Applied Ophthalmobiology (IOBA, Retina Group, 2Ministry of Science and Innovation CIBER-BBN, Statistics Department, 3Clinic University Hospital, University of Valladolid, Valladolid, SpainBackground: Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties.Methods: After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined.Results: Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%. Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5% practiced anterior segment surgery, and 78.7% declared skills in vitrectomy.Conclusion: We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.Keywords: clinical activity, fellowship, mastership, professional profile, retinologist training

Improvement of the organizational support of prevention and counteraction of corruption in the bodies of State Fiscal Service of Ukraine

Directory of Open Access Journals (Sweden)

S. M. Ivasenko

2014-11-01

Full Text Available The article analyses directions of perfection of organizational support of prevention and counteraction of corruption in the bodies of State fiscal service of Ukraine. It is noted that fight against corruption in tax authorities is the most important component of increasing the efficiency of tax administration and tax crime reducing. In its importance it can be equated to such important problems as the fighting against tax crimes. The author, generalizing theoretical approaches, highlights priority activities aimed at improving the efficiency of detecting and exposing corrupt employees of the fiscal authorities.

Erythropoetin receptor expression in the human diabetic retina

Directory of Open Access Journals (Sweden)

Tsang Stephen H

2009-11-01

Full Text Available Abstract Background Recent evidence suggests erythropoietin (EPO and the erythropoietin receptor (EPOR may play a direct role in the pathogenesis of diabetic retinopathy. Better characterization of the EPO-EPOR signaling system in the ischemic retina may offer a new therapeutic modality for ischemic ophthalmic diseases. This study was performed to identify EPOR mRNA expression in the human diabetic eye. Findings EPOR antisense RNA probes were validated on human pancreas tissue. In the normal eye, EPOR was expressed in the retinal ganglion cell layer. Minimal expression was observed in the inner and outer nuclear layer. Under conditions of diabetic retinopathy, EPOR expression shifted to photoreceptor cells. Increased expression was also observed in the peripheral retina. Conclusion EPOR expression may be a biomarker or contribute to disease mechanisms in diabetic retinopathy.

Sobre la terapia génica para enfermedades de la retina.

Science.gov (United States)

Fischer, M Dominik

2017-07-11

Las mutaciones en un gran número de genes provocan degeneración de la retina y ceguera sin que exista actualmente cura alguna. En las últimas décadas, la terapia génica para enfermedades de la retina ha evolucionado y se ha convertido en un nuevo y prometedor paradigma terapéutico para estas enfermedades poco comunes. Este artículo refleja las ideas y los conceptos que parten de la ciencia básica hacia la aplicabilidad de la terapia génica en el ámbito clínico. Se describen los avances y las reflexiones actuales sobre la eficacia de los ensayos clínicos en la actualidad y se discuten los posibles obstáculos y soluciones de cara al futuro de la terapia génica para enfermedades de la retina. © 2017 S. Karger AG, Basel.

CLRN1 is nonessential in the mouse retina but is required for cochlear hair cell development.

Directory of Open Access Journals (Sweden)

Scott F Geller

2009-08-01

Full Text Available Mutations in the CLRN1 gene cause Usher syndrome type 3 (USH3, a human disease characterized by progressive blindness and deafness. Clarin 1, the protein product of CLRN1, is a four-transmembrane protein predicted to be associated with ribbon synapses of photoreceptors and cochlear hair cells, and recently demonstrated to be associated with the cytoskeleton. To study Clrn1, we created a Clrn1 knockout (KO mouse and characterized the histological and functional consequences of Clrn1 deletion in the retina and cochlea. Clrn1 KO mice do not develop a retinal degeneration phenotype, but exhibit progressive loss of sensory hair cells in the cochlea and deterioration of the organ of Corti by 4 months. Hair cell stereocilia in KO animals were longer and disorganized by 4 months, and some Clrn1 KO mice exhibited circling behavior by 5-6 months of age. Clrn1 mRNA expression was localized in the retina using in situ hybridization (ISH, laser capture microdissection (LCM, and RT-PCR. Retinal Clrn1 transcripts were found throughout development and adulthood by RT-PCR, although expression peaked at P7 and declined to undetectable levels in adult retina by ISH. LCM localized Clrn1 transcripts to the retinas inner nuclear layer, and WT levels of retinal Clrn1 expression were observed in photoreceptor-less retinas. Examination of Clrn1 KO mice suggests that CLRN1 is unnecessary in the murine retina but essential for normal cochlear development and function. This may reflect a redundancy in the mouse retina not present in human retina. In contrast to mouse KO models of USH1 and USH2, our data indicate that Clrn1 expression in the retina is restricted to the Müller glia. This is a novel finding, as most retinal degeneration associated proteins are expressed in photoreceptors, not in glia. If CLRN1 expression in humans is comparable to the expression pattern observed in mice, this is the first report of an inner retinal protein that, when mutated, causes retinal

Comparative analysis of successful practices of corruption counteraction in the sphere of school education in foreign countries

Directory of Open Access Journals (Sweden)

Valentina Vladimirovna Tereshkova

2015-03-01

Full Text Available Objective to analyze the practice of corruption counteraction in the sphere of school education in foreign countries. Methods comparativelegal method polling content analysis of documents expert evaluation testing of experts with an international technique Questionnaire Profile of Demand. Results the need for the corruption counteraction program is stated in Art. 13.3 of the Federal Law ldquoOn corruption counteractionrdquoand Methodological recommendations of the Russian Ministry of Labor on corruption risks evaluation when implementing functions but no definite measures for corruption counteraction in educational organizations have been formulated. Nevertheless the controlling bodies inquire for information on such measures. As an example wecitean inquiry of Krasnoyarsk Oktyabrskiy region Prosecutorrsquos Office to educational organizations of October 21 2014 no. 86012014 ldquoOn measures for corruption counteraction in the sphere of educationrdquo. Scientific novelty summarizing the experience of corruption counteraction in the sphere of education in foreign countries and the expertsrsquo opinion of the specialist of international organizations allowed to formulate a number of recommendations for the Russian educational establishments. Practical value the experience of corruption counteraction in foreign countries will allow the head of an educational establishment to choose those of the proposed measures which will be efficient in corruption prevention and to elaborate an efficient program for corruption prevention. nbsp

Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice.

Science.gov (United States)

Cui, Xuezhi; Navneet, Soumya; Wang, Jing; Roon, Penny; Chen, Wei; Xian, Ming; Smith, Sylvia B

2017-04-01

Hyperhomocysteinemia (Hhcy) is implicated in certain retinal neurovascular diseases, although whether it is causative remains uncertain. In isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal phenotypes in Hhcy mice caused by mutations in remethylation (methylene tetrahydrofolatereductase [Mthfr+/-]) or transsulfuration pathways (cystathionine β-synthase [Cbs+/-]) demonstrate mild GC loss and mild vasculopathy. The current work investigated compensation in vivo of one pathway for the other, and, because the transsulfuration pathway yields cysteine necessary for formation of glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also. Retinas isolated from wild-type (WT), Mthfr+/-, and Cbs+/- mice (12 and 22 weeks) were analyzed for methylene tetrahydrofolate reductase (MTHFR), cystathionine-β-synthase (CBS), and cystathionase (CTH) RNA/protein levels. Retinas were evaluated for levels of reduced:oxidized GSH (GSH:GSSG), Slc7a11 (xCT), taurine, taurine transporter (TAUT), and H2S. Aside from decreased CBS RNA/protein levels in Cbs+/- retinas, there were minimal alterations in remethylation/transsulfuration pathways in the two mutant mice strains. Glutathione and taurine levels in Mthfr+/- and Cbs+/- retinas were similar to WT, which may be due to robust levels of xCT and TAUT in mutant retinas. Interestingly, levels of H2S were markedly increased in retinas of Mthfr+/- and Cbs+/- mice compared with WT. Ganglion cell loss and vasculopathy observed in Mthfr+/- and Cbs+/- mouse retinas may be milder than expected, not because of compensatory increases of enzymes in remethylation/transsulfuration pathways, but because downstream transsulfuration pathway products GSH, taurine, and H2S are maintained at robust levels. Elevation of H2S is particularly intriguing owing to neuroprotective properties reported for this gasotransmitter.

Adaptive colour contrast coding in the salamander retina efficiently matches natural scene statistics.

Directory of Open Access Journals (Sweden)

Genadiy Vasserman

Full Text Available The visual system continually adjusts its sensitivity to the statistical properties of the environment through an adaptation process that starts in the retina. Colour perception and processing is commonly thought to occur mainly in high visual areas, and indeed most evidence for chromatic colour contrast adaptation comes from cortical studies. We show that colour contrast adaptation starts in the retina where ganglion cells adjust their responses to the spectral properties of the environment. We demonstrate that the ganglion cells match their responses to red-blue stimulus combinations according to the relative contrast of each of the input channels by rotating their functional response properties in colour space. Using measurements of the chromatic statistics of natural environments, we show that the retina balances inputs from the two (red and blue stimulated colour channels, as would be expected from theoretical optimal behaviour. Our results suggest that colour is encoded in the retina based on the efficient processing of spectral information that matches spectral combinations in natural scenes on the colour processing level.

The Retina Algorithm

CERN Multimedia

CERN. Geneva; PUNZI, Giovanni

2015-01-01

Charge particle reconstruction is one of the most demanding computational tasks found in HEP, and it becomes increasingly important to perform it in real time. We envision that HEP would greatly benefit from achieving a long-term goal of making track reconstruction happen transparently as part of the detector readout ("detector-embedded tracking"). We describe here a track-reconstruction approach based on a massively parallel pattern-recognition algorithm, inspired by studies of the processing of visual images by the brain as it happens in nature ('RETINA algorithm'). It turns out that high-quality tracking in large HEP detectors is possible with very small latencies, when this algorithm is implemented in specialized processors, based on current state-of-the-art, high-speed/high-bandwidth digital devices.

Glycinergic pathways in the goldfish retina

International Nuclear Information System (INIS)

Marc, R.E.; Lam, D.M.

1981-01-01

Autoradiographic localization of high affinity [3H]glycine uptake in the retina of the goldfish has been used to study some anatomical and physiological properties of potentially glycinergic neurons. There are two classes of retinal cells exhibiting high affinity glycine uptake: Aa amacrine cells and I2 interplexiform cells. Aa amacrine cells constitute about 20% of the somas in the amacrine cell layer and send their dendrites to the middle of the inner plexiform layer. There they are both pre- and postsynaptic primarily to other amacrine cells. Photic modulation of glycine uptake indicates that they are probably red-hyperpolarizing/green-depolarizing neurons. I2 interplexiform cells are a newly discovered type of interplexiform cell; in the outer plexiform layer, they receive direct synaptic input from the somas of red-dominated GABAergic H1 horizontal cells and are apparently presynaptic to dendrites of unidentified types of horizontal cells. The connections of I2 interplexiform cells have not been successfully characterized in the inner plexiform layer. These findings extend our knowledge of neurochemically specific pathways in the cyprinid retina and indicate that glycine, like GABA, is a neurotransmitter primarily involved with circuits coding ''red'' information

Testing can counteract proactive interference by integrating competing information

Science.gov (United States)

Wahlheim, Christopher N.

2015-01-01

Testing initially learned information before presenting new information has been shown to counteract the deleterious effects of proactive interference by segregating competing sources of information. The present experiments were conducted to demonstrate that testing can also have its effects in part by integrating competing information. Variations of classic A–B, A–D paired-associate learning paradigms were employed that included two lists of word pairs and a cued-recall test. Repeated pairs appeared in both lists (A–B, A–B), control pairs appeared in List 2 only (A–B, C–D), and changed pairs appeared with the same cue in both lists but with different responses (A–B, A–D). The critical manipulation was whether pairs were tested or restudied in an interpolated phase that occurred between Lists 1 and 2. On a final cued-recall test, participants recalled List 2 responses and then indicated when they recollected that responses had earlier changed between lists. The change recollection measure indexed the extent to which competing responses were integrated during List 2. Change was recollected more often for tested than for restudied pairs. Proactive facilitation was obtained in cued recall when change was recollected, whereas proactive interference was obtained when change was not recollected. These results provide evidence that testing counteracted proactive interference in part by making List 1 responses more accessible during List 2, thus promoting integration and increasing later recollection of change. These results have theoretical implications because they show that testing can counteract proactive interference by integrating or segregating competing information. PMID:25120241

Testing can counteract proactive interference by integrating competing information.

Science.gov (United States)

Wahlheim, Christopher N

2015-01-01

Testing initially learned information before presenting new information has been shown to counteract the deleterious effects of proactive interference by segregating competing sources of information. The present experiments were conducted to demonstrate that testing can also have its effects in part by integrating competing information. Variations of classic A-B, A-D paired-associate learning paradigms were employed that included two lists of word pairs and a cued-recall test. Repeated pairs appeared in both lists (A-B, A-B), control pairs appeared in List 2 only (A-B, C-D), and changed pairs appeared with the same cue in both lists but with different responses (A-B, A-D). The critical manipulation was whether pairs were tested or restudied in an interpolated phase that occurred between Lists 1 and 2. On a final cued-recall test, participants recalled List 2 responses and then indicated when they recollected that responses had earlier changed between lists. The change recollection measure indexed the extent to which competing responses were integrated during List 2. Change was recollected more often for tested than for restudied pairs. Proactive facilitation was obtained in cued recall when change was recollected, whereas proactive interference was obtained when change was not recollected. These results provide evidence that testing counteracted proactive interference in part by making List 1 responses more accessible during List 2, thus promoting integration and increasing later recollection of change. These results have theoretical implications because they show that testing can counteract proactive interference by integrating or segregating competing information.

Atrofia girata de coróide e retina : relato de caso

Directory of Open Access Journals (Sweden)

Oyamaguchi Emerson Kenji

2003-01-01

Full Text Available OBJETIVO: Relatar um caso de atrofia girata de coróide e retina com confirmação por meio da bioquímica do plasma. MÉTODO: Aferiu-se a melhor acuidade visual corrigida de ambos olhos (AO em tabela de Snellen. Foram realizados biomicroscopia do segmento anterior, refração, mapeamento de retina, angiografia fluoresceínica, campo visual e dosagem da ornitina sérica (aminoacidograma. RESULTADOS: Paciente de 22 anos, sexo feminino, cor branca, apresentando alta miopia e acuidade visual (AV 20/100 em AO. À biomicroscopia do segmento anterior apresentava catarata subcapsular posterior em AO. À oftalmoscopia foram verificadas lesões atróficas da coróide e da retina bem delimitadas em meia periferia de AO. O aminoacidograma constatou elevação correspondente ao complexo da ornitina. CONCLUSÃO: Relata-se um caso típico de atrofia girata, distrofia retiniana rara associada a hiperornitinemia.

Melatonin counteracts changes in hypothalamic gene expression of signals regulating feeding behavior in high-fat fed rats.

Science.gov (United States)

Ríos-Lugo, María J; Jiménez-Ortega, Vanesa; Cano-Barquilla, Pilar; Mateos, Pilar Fernández; Spinedi, Eduardo J; Cardinali, Daniel P; Esquifino, Ana I

2015-03-01

Previous studies indicate that the administration of melatonin caused body weight and abdominal visceral fat reductions in rodent models of hyperadiposity. The objective of the present study performed in high-fat fed rats was to evaluate the activity of melatonin on gene expression of some medial basal hypothalamus (MBH) signals involved in feeding behavior regulation, including neuropeptide Y (NPY), proopiomelanocortin (POMC), prolactin-releasing peptide (PrRP), leptin- and insulin-receptors (R) and insulin-R substrate (IRS)-1 and -2. Blood levels of leptin and adiponectin were also measured. Adult Wistar male rats were divided into four groups (n=16 per group): (i) control diet (3% fat); (ii) high-fat (35%) diet; (iii) high-fat diet+melatonin; (iv) control diet+melatonin. Rats had free access to high-fat or control chow and one of the following drinking solutions: (a) tap water; (b) 25 μg/mL of melatonin. After 10 weeks, the high-fat fed rats showed augmented MBH mRNA levels of NPY, leptin-R, PrRP, insulin-R, IRS-1 and IRS-2. The concomitant administration of melatonin counteracted this increase. Feeding of rats with a high-fat diet augmented expression of the MBH POMC gene through an effect insensitive to melatonin treatment. The augmented levels of circulating leptin and adiponectin seen in high-fat fed rats were counteracted by melatonin as was the augmented body weight: melatonin significantly attenuated a body weight increase in high-fat fed rats without affecting chow or water consumption. Melatonin augmented plasma leptin and adiponectin in control rats. The results indicate that an effect on gene expression of feeding behavior signals at the central nervous system (CNS) may complement a peripheral rise of the energy expenditure produced by melatonin to decrease body weight in high-fat fed rats.

Linezolid-induced optic neuropathy with a rare pathological change in the inner retina.

Science.gov (United States)

Ishii, Nobuhito; Kinouchi, Reiko; Inoue, Masatomo; Yoshida, Akitoshi

2016-12-01

We report a case of linezolid-induced optic neuropathy with transient microcystic spaces in the inner retina. We observed the retina using Fourier-domain optical coherence tomography (FD-OCT) in a patient with linezolid-induced optic neuropathy. A 49-year-old woman presented to our department with a 1-week history of bilateral photophobia. At the first visit, her best-corrected visual acuity (VA) was 0.6 in the right eye and 0.5 in the left eye. She had moderate optic disk edema and central scotomas bilaterally. FD-OCT showed bilateral microcystic spaces in the retina. Microcystic spaces were seen in the retinal nerve fiber layer (RNFL) and at the border of the RNFL and the retinal ganglion cell layer. Magnetic resonance imaging and laboratory tests showed no positive findings except for an elevated lactic acid level. One week after the first visit, the VA levels decreased to 0.06 and 0.07 in the right and left eyes, respectively. Because the patient had a 7-month history of linezolid treatment for persistent pyogenic arthritis, we suspected linezolid-induced optic neuropathy and immediately terminated treatment with this drug. The optic disk edema and the microcystic spaces in the retina resolved, and the VA improved to 1.2 at 6 weeks after linezolid withdrawal. Microcystic spaces, which resolved with linezolid withdrawal, were observed in linezolid-induced optic neuropathy. The microcystic spaces in the inner retina can be the first retinal sign of some optic neuropathies.

Comparative proteomic analyses of macular and peripheral retina of cynomolgus monkeys (Macaca fascicularis).

Science.gov (United States)

Okamoto, Haru; Umeda, Shinsuke; Nozawa, Takehiro; Suzuki, Michihiro T; Yoshikawa, Yasuhiro; Matsuura, Etsuko T; Iwata, Takeshi

2010-01-01

The central region of the primate retina is called the macula. The fovea is located at the center of the macula, where the photoreceptors are concentrated to create a neural network adapted for high visual acuity. Damage to the fovea, e.g., by macular dystrophies and age-related macular degeneration, can reduce central visual acuity. The molecular mechanisms leading to these diseases are most likely dependent on the proteins in the macula which differ from those in the peripheral retina in expression level. To investigate whether the distribution of proteins in the macula is different from the peripheral retina, proteomic analyses of tissues from these two regions of cynomolgus monkeys were compared. Two-dimensional gel electrophoresis and mass spectrometry identified 26 proteins that were present only in the macular gel spots. The expression levels of five proteins, cone photoreceptor specific arrestin-C, gamma-synuclein, epidermal fatty acid binding protein, tropomyosin 1alpha chain, and heterogeneous nuclear ribonucleoproteins A2/B1, were significantly higher in the macula than in the peripheral retina. Immunostaining of macula sections by antibodies to each identified protein revealed unique localization in the retina, retinal pigment epithelial cells and the choroidal layer. Some of these proteins were located in cells with higher densities in the macula. We suggest that it will be important to study these proteins to determine their contribution to the pathogenesis and progression of macula diseases.

Nature gives us strength: exposure to nature counteracts ego-depletion.

Science.gov (United States)

Chow, Jason T; Lau, Shun

2015-01-01

Previous research rarely investigated the role of physical environment in counteracting ego-depletion. In the present research, we hypothesized that exposure to natural environment counteracts ego-depletion. Three experiments were conducted to test this hypothesis. In Experiment 1, initially depleted participants who viewed pictures of nature scenes showed greater persistence on a subsequent anagram task than those who were given a rest period. Experiment 2 expanded upon this finding by showing that natural environment enhanced logical reasoning performance after ego-depleting task. Experiment 3 adopted a two- (depletion vs. no-depletion) -by-two (nature exposure vs. urban exposure) factorial design. We found that nature exposure moderated the effect of depletion on anagram task performance. Taken together, the present studies offer a viable and novel strategy to mitigate the negative impacts of ego-depletion.

Defects in the outer limiting membrane are associated with rosette development in the Nrl-/- retina.

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Michael W Stuck

Full Text Available The neural retinal leucine zipper (Nrl knockout mouse is a widely used model to study cone photoreceptor development, physiology, and molecular biology in the absence of rods. In the Nrl(-/- retina, rods are converted into functional cone-like cells. The Nrl(-/- retina is characterized by large undulations of the outer nuclear layer (ONL commonly known as rosettes. Here we explore the mechanism of rosette development in the Nrl(-/- retina. We report that rosettes first appear at postnatal day (P8, and that the structure of nascent rosettes is morphologically distinct from what is seen in the adult retina. The lumen of these nascent rosettes contains a population of aberrant cells protruding into the subretinal space that induce infolding of the ONL. Morphologically adult rosettes do not contain any cell bodies and are first detected at P15. The cells found in nascent rosettes are photoreceptors in origin but lack inner and outer segments. We show that the adherens junctions between photoreceptors and Müller glia which comprise the retinal outer limiting membrane (OLM are not uniformly formed in the Nrl(-/- retina and thus allow protrusion of a population of developing photoreceptors into the subretinal space where their maturation becomes delayed. These data suggest that the rosettes of the Nrl(-/- retina arise due to defects in the OLM and delayed maturation of a subset of photoreceptors, and that rods may play an important role in the proper formation of the OLM.

Two-photon excited autofluorescence imaging of freshly isolated frog retinas.

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Lu, Rong-Wen; Li, Yi-Chao; Ye, Tong; Strang, Christianne; Keyser, Kent; Curcio, Christine A; Yao, Xin-Cheng

2011-06-01

The purpose of this study was to investigate cellular sources of autofluorescence signals in freshly isolated frog (Rana pipiens) retinas. Equipped with an ultrafast laser, a laser scanning two-photon excitation fluorescence microscope was employed for sub-cellular resolution examination of both sliced and flat-mounted retinas. Two-photon imaging of retinal slices revealed autofluorescence signals over multiple functional layers, including the photoreceptor layer (PRL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Using flat-mounted retinas, depth-resolved imaging of individual retinal layers further confirmed multiple sources of autofluorescence signals. Cellular structures were clearly observed at the PRL, ONL, INL, and GCL. At the PRL, the autofluorescence was dominantly recorded from the intracellular compartment of the photoreceptors; while mixed intracellular and extracellular autofluorescence signals were observed at the ONL, INL, and GCL. High resolution autofluorescence imaging clearly revealed mosaic organization of rod and cone photoreceptors; and sub-cellular bright autofluorescence spots, which might relate to connecting cilium, was observed in the cone photoreceptors only. Moreover, single-cone and double-cone outer segments could be directly differentiated.

Circulating Reactive Oxidant Causes Apoptosis of Retinal Pigment Epithelium and Cone Photoreceptors in the Mouse Central Retina

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Wei Wang

2011-01-01

Full Text Available Reactive oxidants damage the retinal pigment epithelium (RPE, which is required for viability of overlying photoreceptors. Smoking which leads to chronic accumulation of reactive oxidants in the circulation is linked to age-related macular degeneration (AMD where RPE death is seen along with photoreceptor loss in the central macular region of the retina. It is unclear why this damage is concentrated in the central retina. We asked whether circulating oxidant might specifically target the central retina. Mice were administered the classic reactive oxidant iodate through tail vein injection, and visual acuity was followed by optokinetic response. Histology and apoptosis was examined by H&E and immunostaining. Iodate indeed selectively damaged the central retina, and this damage was highlighted by early apoptosis of RPE in the central retina followed by apoptosis of photoreceptors adjacent to the region of RPE loss–-cones were lost preferentially. The pattern and extent of this damage was independent of exposure to light. We then conclude that circulating oxidant is sufficient to selectively damage the central retina highlighted by sequential apoptosis of RPE and photoreceptors, with cones being the most sensitivity to this RPE loss.

Preservation of Retina Ganglion Cell Function by Morphine in a Chronic Ocular-Hypertensive Rat Model

OpenAIRE

Husain, Shahid; Abdul, Yasir; Crosson, Craig E.

2012-01-01

Morphine, a broad range opioid-receptors agonist, provides retina neuroprotection against glaucomatous injury in chronic experimental rat model. Morphine-induced retina neuroprotection in glaucoma model is mediated partly via inhibition of TNF-alpha production and caspase-3 and caspase-8 activation.

Fotocoagulação a laser em pacientes portadores de descolamento de retina regmatogênico periférico

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Paulo Escarião

2013-08-01

Full Text Available OBJETIVO: Relatar uma série de casos de descolamento de retina sem envolvimento macular tratados com fotocoagulação a laser. MÉTODOS: Estudo tipo série de casos envolvendo 14 olhos de 12 pacientes com descolamento de retina regmatogênico sem envolvimento macular, retrospectivo, de intervenção. Olhos com procedimentos cirúrgicos prévios foram excluídos. A fotocoagulação a laser foi aplicada com três fileiras confluentes de spot de 300μm, posterior ao descolamento de retina, se extendendo até a ora serrata. A melhor acuidade visual corrigida pré e pós-operatória e a progressão do descolamento de retina foram registrados durante o estudo. RESULTADOS: Treze olhos necessitaram de apenas uma sessão de laser para conter o descolamento de retina. Apenas um olho necessitou de intervenção adicional por causa da evolução do descolamento de retina. Miopia foi encontrada em 7 olhos. Todos os pacientes mantiveram acuidade visual corrigida igual ou melhor que 20/30. CONCLUSÃO:Em casos bem selecionados, a fotocoagulação a laser pode ser considerada para o tratamento de descolamento de retina regmatogênico.

Simulating the Effects of Laser Damage to the Retina

National Research Council Canada - National Science Library

2001-01-01

This Phase II SBIR brought vision and signal processing researchers from the Air Force, academia and the public sector together to develop a visualization tool for modeling laser damage to the retina...

Excess lead in the neural retina in age-related macular degeneration.

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Erie, Jay C; Good, Jonathan A; Butz, John A

2009-12-01

To measure lead and cadmium in retinal tissues of human donor eyes with and without age-related macular degeneration (AMD). Laboratory investigation. Lead and cadmium concentrations in retinal tissues (neural retina and retinal pigment epithelium [RPE]-choroid complex) in 25 subjects with AMD (50 donor eyes) and 36 normal subjects (72 donor eyes) were determined by using inductively coupled plasma-mass spectrometry. Severity of AMD was graded by using color fundus photographs and the Minnesota Grading System. Differences in metal concentrations were compared by using Wilcoxon rank-sum tests. The neural retinas of subjects with AMD had increased lead concentrations (median, 12.0 ng/g; 25% to 75% interquartile range, 8 to 18 ng/g; n = 25) compared with normal subjects (median, 8.0 ng/g; 25% to 75% interquartile range, 0 to 11 ng/g; P = .04; n = 36). There was no difference in lead concentration in the RPE-choroid complex between subjects with AMD (median, 198 ng/g; 25% to 75% interquartile range, 87 to 381 ng/g) and normal subjects (median, 172 ng/g; 25% to 75% interquartile range, 100 to 288 ng/g; P = .25). Cadmium concentration in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.8 microg/g) and RPE-choroid complex (median, 2.2 microg/g; 25% to 75% interquartile range, 1.8 to 3.7 microg/g) in subjects with AMD was not different from concentrations in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.4 microg/g; P = .32) and RPE-choroid complex (median, 1.5 microg/g; 25% to 75% interquartile range, 0.9 to 2.5 microg/g; P = .12) of normal subjects. AMD is associated with excess lead in the neural retina, and this relationship suggests that metal homeostasis in AMD eyes is different from normal.

COUNTERACTING AGE STEREOTYPES: A SELF-AWARENESS MANIPULATION

OpenAIRE

Chen, Yiwei; Pethtel, Olivia; Ma, Xiaodong

2010-01-01

The major goals of the present study were to (a) examine age differences in susceptibility to age stereotypes and (b) test a self-awareness manipulation in counteracting age stereotypes. Young and older adults read two sets of descriptors that only differed in the to-be-ignored age-related information. In the high self-awareness condition, participants saw themselves via a computer video camera. In the low self-awareness condition, they saw prerecorded images of a stranger. Overall, older adu...

Myopathy associated with pigmentary degeneration of the retina and high protein content of cerebrospinal fluid Miopatia associada a degeneração pigmentar da retina e hiperproteinorraquia

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José Antonio Levy

1974-06-01

Full Text Available The cases of two brothers suffering from a myopathy associated with pigmentary degeneration of the retina and increase of protein content of the cerebrospinal fluid are reported.Foram estudados dois pacientes, filhos de pais não consanguíneos, com quadro miopático, iniciado na segunda década da vida, com predomínio na musculatura das cinturas e da face. Em ambos os casos havia degeneração pigmentar da retina e aumento da taxa protéica no líquido cefalorraqueano.

Light regulation of the insulin receptor in the retina.

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Rajala, Raju V S; Anderson, Robert E

2003-10-01

The peptide hormone insulin binds its cognate cell-surface receptors to activate a coordinated biochemical-signaling network and to induce intracellular events. The retina is an integral part of the central nervous system and is known to contain insulin receptors, although their function is unknown. This article, describes recent studies that link the photobleaching of rhodopsin to tyrosine phosphorylation of the insulin receptor and subsequent activation of phosphoinositide 3- kinase (PI3K). We recently found a light-dependent increase in tyrosine phosphorylation of the insulin receptor-beta-subunit (IR beta) and an increase in PI3K enzyme activity in isolated rod outer segments (ROS) and in anti-phosphotyrosine (PY) and anti-IR beta immunoprecipitates of retinal homogenates. The light effect, which was localized to photoreceptor neurons, is independent of insulin secretion. Our results suggest that light induces tyrosine phosphorylation of IR beta in outer-segment membranes, which leads to the binding of p85 through its N-terminal SH2 domain and the generation of PI-3,4,5-P3. We suggest that the physiological role of this process may be to provide neuroprotection of the retina against light damage by activating proteins that protect against stress-induced apoptosis. The studies linking PI3K activation through tyrosine phosphorylation of IR beta now provide physiological relevance for the presence of these receptors in the retina.

Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.

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Omori, Yoshihiro; Katoh, Kimiko; Sato, Shigeru; Muranishi, Yuki; Chaya, Taro; Onishi, Akishi; Minami, Takashi; Fujikado, Takashi; Furukawa, Takahisa

2011-01-01

In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease.

Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.

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Yoshihiro Omori

Full Text Available In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease.

Effects of hyperbaric oxygen on crystalline lens and retina in nicotine-exposed rats.

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Ari, Seyhmus; Nergiz, Yusuf; Cingü, Abdullah Kürşat; Atay, Ahmet Engin; Sahin, Alparslan; Cinar, Yasin; Caca, Ihsan

2013-03-01

To determine histopathological changes on crystalline lens and retina of rats after subcutaneous injection of nicotine and to examine the effects of hyperbaric oxygen (HBO) on these changes related to nicotine exposure. Twenty-eight female Sprague-Dawley rats were enrolled in the study and the rats were divided into four equal sized groups randomly (Group N: the rats exposed only to nicotine, group HB: the rats received only HBO, group N+HB: the rats that underwent to nicotine injection and subsequently received HBO, group C: the control group that neither exposed to nicotine nor received HBO). The rats were sacrificed by decapitation method and all were enucleated immediately after scarification. Tissue samples from crystalline lens, lens capsule, and the retina from the right eyes of the rats were examined by light microscopy. While the histological appearances of the retina and the lens was similar in group HB, group N+HB, and the control group; group N showed some pathological changes like decrement in the retinal ganglion cell density, atrophy of the retinal nerve fiber layer, congestion of the vessels in the optic nerve head, thinning of the internal plexiform layer, thinning of the lens capsule, and transformation of the anterior subcapsular epithelium into squamous epithelia. Subcutaneous injection of nicotine was found to be related with some pathological changes in the retina and lens of the Sprague-Dawley rats. However HBO caused no significant negative effect. Furthermore, the histopathological changes related to nicotine exposure in the lens and retina of the rats recovered by the application of HBO.

Effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats

Institute of Scientific and Technical Information of China (English)

Xiao Liu

2016-01-01

ABSTRACT Objective:To study the effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats.Methods:SD rats were selected as experimental animals and divided into control group, model group and ozone group, and after diabetic models were built, ozone enema was conducted. Retina tissue was collected, TUNEL kits were used to detect the number of apoptotic cells, and Elisa kits were used to detect the contents of nerve damage molecules, angiogenesis-related molecules and endoplasmic reticulum stress molecules. Results:The number of apoptotic cells in retina tissue of model group was significantly more than that of control group, and the number of apoptotic cells in retina tissue of ozone group was significantly less than that of model group; NgR, NR2B, ERK1, ERK2, GFAP, VEGF, STAT-3, HIF-1α, Apelin, APJ, PERK, IRE-1α, ATF-6, eIF2α and XBP-1 contents in retina tissue of model group were significantly higher than those of control group, and PEDF content was lower than that of control group; NgR, NR2B, ERK1, ERK2, GFAP, VEGF, STAT-3, HIF-1α, Apelin, APJ, PERK, IRE-1α, ATF-6, eIF2α and XBP-1 contents in retina tissue of ozone group were significantly lower than those of model group, and PEDF content was higher than that of model group.Conclusion:Ozone therapy can reduce the number of apoptotic cells while reduce nerve cell injury and inhibit angiogenesis and endoplasmic reticulum stress in retina tissue of diabetic rats.

Effects and Responses to Spaceflight in the Mouse Retina

Science.gov (United States)

Zanello, Susana B.; Theriot, Corey; Westby, Christian; Boyle, Richard

2011-01-01

Several stress environmental factors are combined in a unique fashion during spaceflight, affecting living beings widely across their physiological systems. Recently, attention has been placed on vision changes in astronauts returning from long duration missions. Alterations include hyperoptic shift, globe flattening, choroidal folds and optic disc edema, which are probably associated with increased intracranial pressure. These observations justify a better characterization of the ocular health risks associated with spaceflight. This study investigates the impact of spaceflight on the biology of the mouse retina. Within a successful tissue sharing effort, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (Animal Enclosure Module) mice were used as ground controls. Oxidative stress-induced DNA damage was higher in the flight samples compared to controls on R+1, and decreased on R+7. A trend toward higher oxidative and cellular stress response gene expression was also observed on R+1 compared to AEM controls, and these levels decreased on R+7. Several genes coding for key antioxidant enzymes, namely, heme-oxygenase-1, peroxiredoxin, and catalase, were among those upregulated after flight. Likewise, NF B and TGFbeta1, were upregulated in one flight specimen that overall showed the most elevated oxidative stress markers on R+1. In addition, retinas from vivarium control mice evidenced higher oxidative stress markers, NF B and TGFbeta1, likely due to the more intense illumination in vivarium cages versus the AEM. These preliminary data suggest that spaceflight represents a source of environmental stress that translates into oxidative and cellular stress in the retina, which is partially reversible upon return to Earth. Further work is needed to dissect the contribution of the various spaceflight factors (microgravity, radiation) and to

Increased expression of IRE1α and stress-related signal transduction proteins in ischemia-reperfusion injured retina

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Natsuyo Hata

2008-08-01

Full Text Available Natsuyo Hata1, Toshiyuki Oshitari1,2, Akiko Yokoyama1,3, Yoshinori Mitamura1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 3Department of Ophthalmology, Inoue Memorial Hospital, Chuo-ku, Chiba, JapanAbstract: The purpose of this study was to determine whether the expression of ER stress-related factors IRE1α, apoptosis signal-regulating kinase 1 (ASK1, SAPK/ERK kinase 1 (SEK1 and c-Jun N-terminal kinase (JNK is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1α, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1α immunoreactivity in the ganglion cell layer (GCL were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.Keywords: endoplasmic reticulum, IRE1α, apoptosis signal-regulating kinase 1, SAPK/ERK kinase 1, c-Jun N-terminal kinase, Fluoro-Jade B, ischemia-reperfusion injury

Bipolar cell gap junctions serve major signaling pathways in the human retina.

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Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

2017-08-01

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain

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Jean-François Bouchard

2016-01-01

Full Text Available Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system. Cannabinoid receptors are seven transmembrane G-protein coupled receptors favoring Gi/o protein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function. In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing. The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far. It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Müller cells. The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases.

[Lattice degeneration of the retina].

Science.gov (United States)

Boĭko, E V; Suetov, A A; Mal'tsev, D S

2014-01-01

Lattice degeneration of the retina is a clinically important type of peripheral retinal dystrophies due to its participation in the pathogenesis of rhegmatogenous retinal detachment. In spite of extensive epidemiological, morphological, and clinical data, the question on causes of this particular type of retinal dystrophies currently remains debatable. Existing hypotheses on pathogenesis of retinal structural changes in lattice degeneration explain it to a certain extent. In clinical ophthalmology it is necessary to pay close attention to this kind of degenerations and distinguish between cases requiring preventive treatment and those requiring monitoring.

Lipid nanoparticles as drug/gene delivery systems to the retina.

Science.gov (United States)

del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

2013-03-01

This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.

Avaliação da autofluorescência do fundo de olho nas distrofias de retina com o aparelho Heidelberg Retina Angiograph2 Evaluation of fundus autofluorescence in hereditary retinal diseases using Heidelberg Retina Angiograph2

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Monique Côco

2007-10-01

Full Text Available OBJETIVOS: Definir características do exame de autofluorescência, verificando sua utilidade no diagnóstico e acompanhamento de distrofias retinianas. MÉTODOS: Participaram do estudo, 28 pacientes, adultos, divididos igualmente em quatro grupos com diagnósticos de doença de Stargardt, distrofia de Cones, retinose pigmentar e voluntários saudáveis para estabelecimento do padrão de normalidade. Em média foram obtidas nove imagens com o filtro para angiofluoresceinografia para a formação da imagem autofluorescente no Heidelberg Retina Angiograph2. As imagens de cada grupo de pacientes foram analisadas para verificar características comuns. RESULTADOS: As imagens fundoscópicas autofluorescentes dos voluntários do grupo controle mostraram área foveal hipoautofluorescente em relação à retina do pólo posterior. As imagens dos portadores de doença de Stargardt, em geral, apresentaram lesão hipoautofluorescente, correspondendo à área macular. As principais alterações da autofluorescência em pacientes com distrofia de cones foram hipoautofluorescência macular com halo hiperautofluorescente. Nos portadores de retinose pigmentar, foram encontrados pigmentos periféricos causando hipoautofluorescência. Na região macular, hipoautofluorescência ou apenas desorganização do pigmento. CONCLUSÃO: O estudo mostrou a existência de padrões de autofluorescência de fundo nas distrofias de retina que permitem o diagnóstico e melhor interpretação da fisiopatogenia destas doenças.PURPOSE: To define characteristics of the fundus autofluorescence examination, verifying usefulness in the diagnosis and care of hereditary retinal diseases. METHODS: 28 patients, adults, divided equally into four groups with diagnoses of Stargardt macular dystrophy, cone dystrophy, retinitis pigmentosa and healthy volunteers for the establishment of the normality pattern. An average of nine images with the filter for fluorescein angiography was obtained

An analog VLSI chip emulating polarization vision of Octopus retina.

Science.gov (United States)

Momeni, Massoud; Titus, Albert H

2006-01-01

Biological systems provide a wealth of information which form the basis for human-made artificial systems. In this work, the visual system of Octopus is investigated and its polarization sensitivity mimicked. While in actual Octopus retina, polarization vision is mainly based on the orthogonal arrangement of its photoreceptors, our implementation uses a birefringent micropolarizer made of YVO4 and mounted on a CMOS chip with neuromorphic circuitry to process linearly polarized light. Arranged in an 8 x 5 array with two photodiodes per pixel, each consuming typically 10 microW, this circuitry mimics both the functionality of individual Octopus retina cells by computing the state of polarization and the interconnection of these cells through a bias-controllable resistive network.

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

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Yanhe Wang

2017-11-01

Full Text Available Background/Aims: Retinitis pigmentosa (RP is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Methods: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1 mice. Results: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Conclusions: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

Modelación y simulación de la retina humana

OpenAIRE

Andrés Castaño; Camilo Montenegro; Carlos Molina; Sergio Mejía

2001-01-01

Las enfermedades de la retina causan pérdida de la visión de varios
grados de severidad; las causas son múltiples y en la mayoría de los casos irreversibles. En los últimos años se ha venido desarrollando investigación en el campo de la visión artificial y la visión por computador, alrededor de todo el mundo. Nuestro proyecto pretende desarrollar un modelo matemático de la retina, implementar la solución numérica en MATLAB™ y posteriormente construir un dispositivo electró...

Degenerações periféricas da retina em pacientes candidatos à cirurgia refrativa Peripheral retina degeneration in patients who are candidates for refractive surgery

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Paulo Henrique de Avila Morales

2001-02-01

Full Text Available Objetivo: O objetivo desse estudo é verificar em indivíduos míopes candidatos à cirurgia refrativa a prevalência dos diferentes tipos de lesões retinianas periféricas degenerativas de acordo com o tipo de miopia. Métodos: De forma prospectiva, no período de um ano, foram examinados os olhos dos pacientes no Setor de Cirurgia Refrativa do Departamento de Oftalmologia da Universidade Federal de São Paulo - Escola Paulista de Medicina que durante a sua consulta inicial apresentassem refração com equivalente esférico superior ou igual a -1,00 dioptria esférica, e não tivessem antecedentes pessoais de doença ou cirurgia ocular no período. Foi investigada a existência de lesões e/ou degenerações periféricas predisponentes ao descolamento regmatogênico de retina. Resultados: O grupo foi composto, em sua maioria, por adultos jovens (média de idade de 31 anos. Foram observados olhos com miopia baixa (263 olhos, 31%, moderada (300 olhos, 36% e alta (277 olhos, 33%; em 35,4% dos pacientes (27% dos olhos foram encontradas degenerações periféricas, sendo o branco com e sem pressão a alteração mais freqüente (23,4% dos pacientes ou 17,5% dos olhos. Entre as lesões predisponentes ao descolamento regmatogênico da retina, a mais encontrada foi a degeneração em treliça (8,6% dos pacientes ou 6% dos olhos. Conclusões: As alterações periféricas predisponentes ou não ao descolamento regmatogênico de retina apresentaram aumento de prevalência de acordo com o aumento do grau de miopia, com exceção das roturas. Todos os pacientes com miopia alta e candidatos à cirurgia refrativa devem ter a periferia retiniana de ambos os olhos examinada.Purpose: To verify, in myopic individuals who are candidates for refractive surgery, the prevalence of different types of peripheral degenerative lesions of the retina, according to the type of myopia. Methods: Prospectively, during a one-year interval, we examined the eyes of patients in

Adaptation of the Central Retina for High Acuity Vision: Cones, the Fovea and the Avascular Zone

Science.gov (United States)

Provis, Jan M; Dubis, Adam M; Maddess, Ted; Carroll, Joseph

2013-01-01

Presence of a fovea centralis is directly linked to molecular specification of an avascular area in central retina, before the fovea (or `pit') begins to form. Modeling suggests that mechanical forces, generated within the eye, initiate formation of a pit within the avascular area, and its later remodeling in the postnatal period. Within the avascular area the retina is dominated by `midget' circuitry, in which signals are transferred from a single cone to a single bipolar cell, then a single ganglion cell. Thus in inner, central retina there are relatively few lateral connections between neurons. This renders the region adaptable to tangential forces, that translocate of ganglion cells laterally / centrifugally, to form the fovea. Optical coherence tomography enables live imaging of the retina, and shows that there is greater variation in the morphology of foveae in humans than previously thought. This variation is associated with differences in size of the avascular area and appears to be genetically based, but can be modified by environmental factors, including prematurity. Even when the fovea is absent (foveal hypoplasia), cones in central retina adopt an elongated and narrow morphology, enabling them to pack more densely to increase the sampling rate, and to act as more effective waveguides. Given these findings, what then is the adaptive advantage of a fovea? We suggest that the advantages of having a pit in central retina are relatively few, and minor, but together work to enhance acuity. PMID:23500068

Stereotyped Synaptic Connectivity Is Restored during Circuit Repair in the Adult Mammalian Retina.

Science.gov (United States)

Beier, Corinne; Palanker, Daniel; Sher, Alexander

2018-06-04

Proper function of the central nervous system (CNS) depends on the specificity of synaptic connections between cells of various types. Cellular and molecular mechanisms responsible for the establishment and refinement of these connections during development are the subject of an active area of research [1-6]. However, it is unknown if the adult mammalian CNS can form new type-selective synapses following neural injury or disease. Here, we assess whether selective synaptic connections can be reestablished after circuit disruption in the adult mammalian retina. The stereotyped circuitry at the first synapse in the retina, as well as the relatively short distances new neurites must travel compared to other areas of the CNS, make the retina well suited to probing for synaptic specificity during circuit reassembly. Selective connections between short-wavelength sensitive cone photoreceptors (S-cones) and S-cone bipolar cells provides the foundation of the primordial blue-yellow vision, common to all mammals [7-18]. We take advantage of the ground squirrel retina, which has a one-to-one S-cone-to-S-cone-bipolar-cell connection, to test if this connectivity can be reestablished following local photoreceptor loss [8, 19]. We find that after in vivo selective photoreceptor ablation, deafferented S-cone bipolar cells expand their dendritic trees. The new dendrites randomly explore the proper synaptic layer, bypass medium-wavelength sensitive cone photoreceptors (M-cones), and selectively synapse with S-cones. However, non-connected dendrites are not pruned back to resemble unperturbed S-cone bipolar cells. We show, for the first time, that circuit repair in the adult mammalian retina can recreate stereotypic selective wiring. Copyright © 2018 Elsevier Ltd. All rights reserved.

Post-translational processing of synaptophysin in the rat retina is disrupted by diabetes.

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Travis S D'Cruz

Full Text Available Synaptophysin, is an abundant presynaptic protein involved in synaptic vesicle recycling and neurotransmitter release. Previous work shows that its content is significantly reduced in the rat retina by streptozotocin (STZ-diabetes. This study tested the hypothesis that STZ-diabetes alters synaptophysin protein turnover and glycosylation in the rat retina. Whole explant retinas from male Sprague-Dawley rats were used in this study. Rats were made diabetic by a single intraperitoneal STZ injection (65 mg/kg body weight in 10 mM sodium citrate, pH 4.5. mRNA translation was measured using a (35S-methionine labeling assay followed by synaptophysin immunoprecipitation and autoradiography. A pulse-chase study was used to determine the depletion of newly synthesized synaptophysin. Depletion of total synaptophysin was determined after treatment with cycloheximide. Mannose rich N-glycosylated synaptophysin was detected by treating retinal lysates with endoglycosidase H followed by immunoblot analysis. Synaptophysin mRNA translation was significantly increased after 1 month (p<0.001 and 2 months (p<0.05 of STZ-diabetes, compared to age-matched controls. Newly synthesized synaptophysin degradation was significantly accelerated in the retina after 1 and 2 months of diabetes compared to controls (p<0.05. Mannose rich glycosylated synaptophysin was significantly increased after 1 month of STZ-diabetes compared to controls (p<0.05.These data suggest that diabetes increases mRNA translation of synaptophysin in the retina, resulting in an accumulation of mannose rich glycosylated synaptophysin, a transient post-translational state of the protein. This diabetes-induced irregularity in post-translational processing could explain the accelerated degradation of retinal synaptophysin in diabetes.

Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

Science.gov (United States)

Widomska, Justyna; Zareba, Mariusz; Subczynski, Witold Karol

2016-01-01

Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene) and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin). Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls), are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases. PMID:27030822

Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

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Justyna Widomska

2016-01-01

Full Text Available Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin. Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls, are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases.

Localization, distribution, and connectivity of neuropeptide Y in the human and porcine retinas - a comparative study

DEFF Research Database (Denmark)

Christiansen, Anders Tolstrup; Kiilgaard, Jens Folke; Klemp, Kristian

2018-01-01

retinal signaling. These findings extend existing knowledge on NPY and NPY-expressing cells in the human and porcine retina showing a high degree of comparability. The extensive distribution and connectivity of NPY-ir cells described in the present study further highlights the potential importance of NPY......Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell-type, and connectivity has never been conducted in larger mammals including...... humans and pigs. As the pig due to size and cellular composition is a well-suited animal for retinal research, we chose to compare the endogenous NPY system of the human retina to that of pigs to support future research in this field. In the present study, using immunohistochemistry, confocal microscopy...

Correlations between specific patterns of spontaneous activity and stimulation efficiency in degenerated retina.

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Christine Haselier

Full Text Available Retinal prostheses that are currently used to restore vision in patients suffering from retinal degeneration are not adjusted to the changes occurring during the remodeling process of the retina. Recent studies revealed abnormal rhythmic activity in the retina of genetic mouse models of retinitis pigmentosa. Here we describe this abnormal activity also in a pharmacologically-induced (MNU mouse model of retinal degeneration. To investigate how this abnormal activity affects the excitability of retinal ganglion cells, we recorded the electrical activity from whole mounted retinas of rd10 mice and MNU-treated mice using a microelectrode array system and applied biphasic current pulses of different amplitude and duration to stimulate ganglion cells electrically. We show that the electrical stimulation efficiency is strongly reduced in degenerated retinas, in particular when abnormal activity such as oscillations and rhythmic firing of bursts of action potentials can be observed. Using a prestimulus pulse sequence, we could abolish rhythmic retinal activity. Under these conditions, the stimulation efficiency was enhanced in a few cases but not in the majority of tested cells. Nevertheless, this approach supports the idea that modified stimulation protocols could help to improve the efficiency of retinal prostheses in the future.

Expression of Endoplasmic Reticulum Stress-Related Factors in the Retinas of Diabetic Rats

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Shu Yan

2012-01-01

Full Text Available Recent reports show that ER stress plays an important role in diabetic retinopathy (DR, but ER stress is a complicated process involving a network of signaling pathways and hundreds of factors, What factors involved in DR are not yet understood. We selected 89 ER stress factors from more than 200, A rat diabetes model was established by intraperitoneal injection of streptozotocin (STZ. The expression of 89 ER stress-related factors was found in the retinas of diabetic rats, at both 1- and 3-months after development of diabetes, by quantitative real-time polymerase chain reaction arrays. There were significant changes in expression levels of 13 and 12 ER stress-related factors in the diabetic rat retinas in the first and third month after the development of diabetes, Based on the array results, homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1(HERP, and synoviolin(HRD1 were studied further by immunofluorescence and Western blot. Immunofluorescence and Western blot analyses showed that the expression of HERP was reduced in the retinas of diabetic rats in first and third month. The expression of Hrd1 did not change significantly in the retinas of diabetic rats in the first month but was reduced in the third month.

Msx1 is expressed in retina endothelial cells at artery branching sites

OpenAIRE

Miguel Lopes; Olivier Goupille; Cécile Saint Cloment; Benoît Robert

2012-01-01

Summary Msx1 and Msx2 encode homeodomain transcription factors that play a role in several embryonic developmental processes. Previously, we have shown that in the adult mouse, Msx1lacZ is expressed in vascular smooth muscle cells (VSMCs) and pericytes, and that Msx2lacZ is also expressed in VSMCs as well as in a few endothelial cells (ECs). The mouse retina and choroid are two highly vascularized tissues. Vessel alterations in the retina are associated with several human diseases and the ret...

Topical legal aspects of corruption counteraction in public procurement

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Aleksandr Igorevich Zemlin

2015-03-01

Full Text Available Objective to analyze the current developments in the Russian legislation on corruption counteraction and the legislation on public procurement system on this basis to study legal conflicts and gaps and to develop proposals under the provisions of the National AntiCorruption Plan for 2014ndash2015. Methods historical formallegal logical and systemicfunctional structural and contextual approach to the study of law and theoretical propositions concerning the definition nature and characteristics of legal relations arising in the process of and relating to the corruption counteraction in the public procurement system. Results аn aggregate of theoretical conclusions and proposals aimed at perfection of anticorruption legislation and legislation on the contractual public procurement system is presented. Scientific novelty the results of the author39s interpretation of changes in the Russian anticorruption legislation and legislation on the contractual public procurement system existing legal conflicts and gaps. Practical significance developing proposals for improving the standards of anticorruption legislation and legislation on public procurement system under the provisions of the National AntiCorruption Plan for 2014ndash2015. nbsp

The Retinome – Defining a reference transcriptome of the adult mammalian retina/retinal pigment epithelium

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Goetz Thomas

2004-07-01

Full Text Available Abstract Background The mammalian retina is a valuable model system to study neuronal biology in health and disease. To obtain insight into intrinsic processes of the retina, great efforts are directed towards the identification and characterization of transcripts with functional relevance to this tissue. Results With the goal to assemble a first genome-wide reference transcriptome of the adult mammalian retina, referred to as the retinome, we have extracted 13,037 non-redundant annotated genes from nearly 500,000 published datasets on redundant retina/retinal pigment epithelium (RPE transcripts. The data were generated from 27 independent studies employing a wide range of molecular and biocomputational approaches. Comparison to known retina-/RPE-specific pathways and established retinal gene networks suggest that the reference retinome may represent up to 90% of the retinal transcripts. We show that the distribution of retinal genes along the chromosomes is not random but exhibits a higher order organization closely following the previously observed clustering of genes with increased expression. Conclusion The genome wide retinome map offers a rational basis for selecting suggestive candidate genes for hereditary as well as complex retinal diseases facilitating elaborate studies into normal and pathological pathways. To make this unique resource freely available we have built a database providing a query interface to the reference retinome 1.

La retina para el médico no oftalmólogo

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Clara Leonor Varón Plata, MD

2010-01-01

Full Text Available La retina es un tejido fundamental en el órgano de la visión.En este artículo hacemos una revisión sobre la anatomía yfisiología de esta estructura así como sobre las principalespatologías que la pueden afectar, entre ellas: despren-dimiento de retina, retinopatía diabética y la enfermedadmacular relacionada con la edad. Aunque actualmentecontamos con técnicas médicas y quirúrgicas seguras yefectivas para el manejo de estas patologías, aúnrepresentan un reto para la ciencia médica, y en estadosavanzados comprometen seriamente la función visual, porello es de gran importancia que el médico general tengaclaros los conceptos básicos sobre el diagnóstico de estasenfermedades, para realizar una remisión adecuada y así poder evitar al máximo secuelas visuales en el paciente. En este artículo revisamos libros de texto reconocidos y empleando MEDLINE, algunos artículos representativos sobre este tema, para mostrar un panorama general del estado actual, clínico e investigativo, del diagnóstico y tratamientode las enfermedades más importantes que afectan la retina y el vítreo. ______________________________________________________________________The retina is a fundamental tissue of the visual organ. In this article we make a review of the anatomy and physiology of this structure as well as the main pathologies that may affect it like: retinal detachment, diabetic retinopathy, and age related macular degeneration. Although currently there are safe medical and surgical alternatives for the management of these diseases, they still represent a challenge for the medical science, and in advanced stagesthey seriously compromise visual function. For this reason it is of vital importance that the primary care physician has clear concepts about the diagnosis of these diseases, to perform an adequate referral, avoiding visual sequelae as much as possible. In this article we reviewed recognized textbooks and using MEDLINE we found some

Human cadaver retina model for retinal heating during corneal surgery with a femtosecond laser

Science.gov (United States)

Sun, Hui; Fan, Zhongwei; Yun, Jin; Zhao, Tianzhuo; Yan, Ying; Kurtz, Ron M.; Juhasz, Tibor

2014-02-01

Femtosecond lasers are widely used in everyday clinical procedures to perform minimally invasive corneal refractive surgery. The intralase femtosecond laser (AMO Corp. Santa Ana, CA) is a common example of such a laser. In the present study a numerical simulation was developed to quantify the temperature rise in the retina during femtosecond intracorneal surgery. Also, ex-vivo retinal heating due to laser irradiation was measured with an infrared thermal camera (Fluke Corp. Everett, WA) as a validation of the simulation. A computer simulation was developed using Comsol Multiphysics to calculate the temperature rise in the cadaver retina during femtosecond laser corneal surgery. The simulation showed a temperature rise of less than 0.3 degrees for realistic pulse energies for the various repetition rates. Human cadaver retinas were irradiated with a 150 kHz Intralase femtosecond laser and the temperature rise was measured withan infrared thermal camera. Thermal camera measurements are in agreement with the simulation. During routine femtosecond laser corneal surgery with normal clinical parameters, the temperature rise is well beneath the threshold for retina damage. The simulation predictions are in agreement with thermal measurements providing a level of experimental validation.

Light-modulated release of RFamide-like neuropeptides from nervus terminalis axon terminals in the retina of goldfish.

Science.gov (United States)

Fischer, A J; Stell, W K

1997-03-01

The nervus terminalis of teleosts, a cranial nerve anatomically associated with the olfactory system, projects to visual system targets including retina and optic tectum. It is known to contain gonadotropin-releasing hormone and RFamide-like peptides, but its function remains unknown. We have probed nervus terminalis function in goldfish by measuring peptide content in retina and tectum with a radioimmunoassay for A18Famide (neuropeptide AF; bovine morphine-modulating peptide). We found that retinal peptide content increased in the dark and decreased in the light, whereas tectal peptide content decreased in the dark and increased in the light. In addition, RFamide-like peptide content in the retina was transiently decreased by severing both olfactory tracts, increased in light-adapted eyes treated with a GABAergic agonist (isoguvacine), and decreased in dark-adapted eyes treated with GABAergic antagonists (bicuculline and picrotoxin). We also found that RFamide-like peptide release could be induced in dark-adapted isolated-superfused retinas by exposure to light or a high concentration (102.5 mM) of potassium ions. We interpret the increase and decrease in peptide content as reflecting a decrease and increase, respectively, in rate of peptide release. We propose that the release and accumulation of RFamide-like peptides in axon terminals of nervus terminalis processes in the retina are modulated primarily by neurons intrinsic to the retina and regulated by light. Peptide release appears to be inhibited tonically in the dark by GABA acting through GABAA receptors; light facilitates peptide release by disinhibition due to a reduction in GABA release. In addition, we propose that electrical signals originating outside the retina can override these intrinsic release-modulating influences.

Taurine biosynthesis in frog retina: effects of light and dark adaptations

International Nuclear Information System (INIS)

Nishimura, C.; Ida, S.; Kuriyama, K.

1983-01-01

The retinal uptake and metabolism of cysteine, a precursor for taurine biosynthesis, were analysed using the bull frog. The [ 14 C] cysteine uptake into isolated retina had some specific properties: It was rather temperature independent, required Na ions, was inhibited by ouabain but not by dinitrophenol, and exhibited saturation kinetics composed of two components. When retinal homogenate was incubated with 12-30 microM of L-[U- 14 C]cysteine, the accumulation of labeled alanine, cysteine sulfinic acid (CSA), cysteic acid (CA), hypotaurine, and taurine was detected. The metabolic conversions of [ 14 C] cysteine to labeled alanine, hypotaurine, and taurine were linear over 90 minutes. Prolonged light adaptation (3 weeks) induced a significant reduction in the formation of labeled CA, CSA, hypotaurine, and taurine from [ 14 C] cysteine. On the other hand, it was found that in dark-adapted retinae, the formation of labeled taurine from [ 14 C] cysteine increased significantly in spite of the reduction in the formation of labeled CA. These results indicate that biosynthetic pathways exist for taurine from cysteine in frog retina, and that these metabolic pathways are involved in the regulation of retinal taurine content under continuous visual adaptation

Simple Experiments on the Physics of Vision: The Retina

Science.gov (United States)

Cortel, Adolf

2005-01-01

Many simple experiments can be performed in the classroom to explore the physics of vision. Students can learn of the two types of receptive cells (rods and cones), their distribution on the retina and the existence of the blind spot.

Distribution of [35S] taurine in mouse retina after intravitreal and intravascular injection

International Nuclear Information System (INIS)

Pourcho, R.G.

1977-01-01

The distribution of [ 35 S] taurine in mouse retinae was studied by autoradiographic techniques after either intravitreal or intravascular injection. The route of injection did not affect the final localization. The major sites of label accumulation were the outer nuclear layer, the inner nuclear layer, and Mueller cell processes adjacent to the vitreal surface. The distribution was consistent with the interpretation that taurine was localized within two cellular compartments of mouse retina, photoreceptor cells and Mueller cells. (author)

Testbeam results of the first real-time embedded tracking system with artificial retina

Energy Technology Data Exchange (ETDEWEB)

Neri, N., E-mail: nicola.neri@mi.infn.it; Abba, A.; Caponio, F.; Citterio, M.; Coelli, S.; Fu, J.; Merli, A.; Monti, M.; Petruzzo, M.

2017-02-11

We present the testbeam results of the first real-time embedded tracking system based on artificial retina algorithm. The tracking system prototype is capable of fast track reconstruction with a latency of the response below 1 μs and track parameter resolutions that are comparable with the offline results. The artificial retina algorithm was implemented in hardware in a custom data acquisition board based on commercial FPGA. The system was tested successfully using a 180 GeV/c proton beam at the CERN SPS with a maximum track rate of about 280 kHz. Online track parameters were found in good agreement with offline results and with the simulated response. - Highlights: • First real-time tracking system based on artificial retina algorithm tested on beam. • Fast track reconstruction within one microsecond latency and offline like quality. • Fast tracking algorithm implemented in commercial FPGAs.

Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina

Science.gov (United States)

Zhang, Yan; Rha, Jungtae; Jonnal, Ravi S.; Miller, Donald T.

2005-06-01

Although optical coherence tomography (OCT) can axially resolve and detect reflections from individual cells, there are no reports of imaging cells in the living human retina using OCT. To supplement the axial resolution and sensitivity of OCT with the necessary lateral resolution and speed, we developed a novel spectral domain OCT (SD-OCT) camera based on a free-space parallel illumination architecture and equipped with adaptive optics (AO). Conventional flood illumination, also with AO, was integrated into the camera and provided confirmation of the focus position in the retina with an accuracy of ±10.3 μm. Short bursts of narrow B-scans (100x560 μm) of the living retina were subsequently acquired at 500 Hz during dynamic compensation (up to 14 Hz) that successfully corrected the most significant ocular aberrations across a dilated 6 mm pupil. Camera sensitivity (up to 94 dB) was sufficient for observing reflections from essentially all neural layers of the retina. Signal-to-noise of the detected reflection from the photoreceptor layer was highly sensitive to the level of cular aberrations and defocus with changes of 11.4 and 13.1 dB (single pass) observed when the ocular aberrations (astigmatism, 3rd order and higher) were corrected and when the focus was shifted by 200 μm (0.54 diopters) in the retina, respectively. The 3D resolution of the B-scans (3.0x3.0x5.7 μm) is the highest reported to date in the living human eye and was sufficient to observe the interface between the inner and outer segments of individual photoreceptor cells, resolved in both lateral and axial dimensions. However, high contrast speckle, which is intrinsic to OCT, was present throughout the AO parallel SD-OCT B-scans and obstructed correlating retinal reflections to cell-sized retinal structures.

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice.

Science.gov (United States)

Wang, Yanhe; Yin, Zhiyuan; Gao, Lixiong; Sun, Dayu; Hu, Xisu; Xue, Langyue; Dai, Jiaman; Zeng, YuXiao; Chen, Siyu; Pan, Boju; Chen, Min; Xie, Jing; Xu, Haiwei

2017-01-01

Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP. © 2017 The Author(s). Published by S. Karger AG, Basel.

Avaliação ocular multimodal em doenças heredodistróficas e degenerativas da retina Multimodal fundus imaging in heredodystrophic and degenerative diseases of the retina

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Daniela Cavalcanti Ferrara

2009-10-01

Full Text Available A tomografia de coerência óptica incorporou-se gradativamente ao contemporâneo arsenal diagnóstico em Oftalmologia, passando a exercer papel fundamental na investigação e condução de doenças oculares, particularmente na especialidade de Retina e Vítreo. A disponibilização comercial da nova geração de aparelhos, chamada de tomografia de coerência óptica "espectral", baseada em conceito físico distinto que permite a aquisição de imagens em alta velocidade, marcou o início de uma nova era desta tecnologia de investigação auxiliar. Adicionalmente, sua recente combinação com o oftalmoscópio de varredura a laser confocal (confocal scanning laser ophthalmoscope vem propiciando a aquisição de imagens tomográficas guiadas em tempo real pelos diferentes modos de imagem (autofluorescência de fundo, reflectância com luz "infravermelha" e angiografia com fluoresceína ou indocianina verde. A avaliação ocular multimodal (multimodal fundus imaging permite a correlação real e minuciosa de achados da morfologia retiniana e do epitélio pigmentar com dados de estudos angiográficos e de autofluorescência ou reflectância, propiciando assim inferências valiosas sobre a fisiologia do tecido. Neste artigo, discutimos brevemente as possíveis implicações da avaliação ocular multimodal na prática da especialidade de Retina e Vítreo.Optical coherence tomography was progressively incorporated to the contemporary diagnostic arsenal in Ophthalmology, playing a crucial role in the diagnosis and management of eye diseases, particularly in the specialty of retina and vitreous. The commercial availability of the new generation of devices, coined "spectral" optical coherence tomography, which is based in a distinct physical concept that permits high-speed image acquisition, launched a new era for this investigative ancillary tool. In addition, the recent combination of this new technology with a confocal scanning laser ophthalmoscope

The ERK1/2 Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina

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Ghulam Mohammad

2013-01-01

Full Text Available This study was conducted to determine the expression of matrix metalloproteinase-9 (MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in a time-dependent manner and the effect of extracellular-signal-regulated kinases-1/2 (ERK1/2 inhibition on the expressions of MMP-9, TIMP-1, and inflammatory biomarkers in the retinas of diabetic rats. The expression of MMP-9 was quantified by zymography, and the mRNA level of MMP-9 and TIMP-1 was quantified by RT-PCR. The expression of inducible nitric oxide synthase (iNOS, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α was examined by Western blot analysis. MMP-9 expression was significantly higher in diabetic rat retinas compared to controls at all time points.TIMP-1 expression was nonsignificantly upregulated at 1week of diabetes and was significantly downregulated at 4 and 12 weeks of diabetes. Intravitreal administration of the ERK1/2 inhibitor U0126 prior to induction of diabetes decreased ERK1/2 activation, attenuated diabetes-induced upregulation of MMP-9, iNOS, IL-6, and TNF-α and upregulated TIMP-1 expression. In MMP-9 knockout mice, diabetes had no effect on retinal iNOS expression and its level remained unchanged. These data provide evidence that ERK1/2 signaling pathway is involved in MMP-9, iNOS, IL-6, and TNF-α induction in diabetic retinas and suggest that ERK1/2 can be a novel therapeutic target in diabetic retinopathy.

A biochemical basis for induction of retina regeneration by antioxidants.

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Echeverri-Ruiz, Nancy; Haynes, Tracy; Landers, Joseph; Woods, Justin; Gemma, Michael J; Hughes, Michael; Del Rio-Tsonis, Katia

2018-01-15

The use of antioxidants in tissue regeneration has been studied, but their mechanism of action is not well understood. Here, we analyze the role of the antioxidant N-acetylcysteine (NAC) in retina regeneration. Embryonic chicks are able to regenerate their retina after its complete removal from retinal stem/progenitor cells present in the ciliary margin (CM) of the eye only if a source of exogenous factors, such as FGF2, is present. This study shows that NAC modifies the redox status of the CM, initiates self-renewal of the stem/progenitor cells, and induces regeneration in the absence of FGF2. NAC works as an antioxidant by scavenging free radicals either independently or through the synthesis of glutathione (GSH), and/or by reducing oxidized proteins through a thiol disulfide exchange activity. We dissected the mechanism used by NAC to induce regeneration through the use of inhibitors of GSH synthesis and the use of other antioxidants with different biochemical structures and modes of action, and found that NAC induces regeneration through its thiol disulfide exchange activity. Thus, our results provide, for the first time, a biochemical basis for induction of retina regeneration. Furthermore, NAC induction was independent of FGF receptor signaling, but dependent on the MAPK (pErk1/2) pathway. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Light pollution: the possible consequences of excessive illumination on retina.

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Contín, M A; Benedetto, M M; Quinteros-Quintana, M L; Guido, M E

2016-02-01

Light is the visible part of the electromagnetic radiation within a range of 380-780 nm; (400-700 on primates retina). In vertebrates, the retina is adapted to capturing light photons and transmitting this information to other structures in the central nervous system. In mammals, light acts directly on the retina to fulfill two important roles: (1) the visual function through rod and cone photoreceptor cells and (2) non-image forming tasks, such as the synchronization of circadian rhythms to a 24 h solar cycle, pineal melatonin suppression and pupil light reflexes. However, the excess of illumination may cause retinal degeneration or accelerate genetic retinal diseases. In the last century human society has increased its exposure to artificial illumination, producing changes in the Light/Dark cycle, as well as in light wavelengths and intensities. Although, the consequences of unnatural illumination or light pollution have been underestimated by modern society in its way of life, light pollution may have a strong impact on people's health. The effects of artificial light sources could have direct consequences on retinal health. Constant exposure to different wavelengths and intensities of light promoted by light pollution may produce retinal degeneration as a consequence of photoreceptor or retinal pigment epithelium cells death. In this review we summarize the different mechanisms of retinal damage related to the light exposure, which generates light pollution.

Degenerações periféricas da retina do olho míope X LASIK

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Nassaralla Jr. João J.

2004-01-01

Full Text Available O objetivo deste artigo é apresentar as degenerações periféricas mais comuns na retina dos olhos míopes, discutindo aquelas que oferecem maiores riscos para o descolamento regmatogênico da retina, seu relacionamento com a cirurgia de LASIK e a indicação para o tratamento profilático.

Alterations in energy metabolism, neuroprotection and visual signal transduction in the retina of Parkinsonian, MPTP-treated monkeys.

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Laura Campello

Full Text Available Parkinson disease is mainly characterized by the degeneration of dopaminergic neurons in the central nervous system, including the retina. Different interrelated molecular mechanisms underlying Parkinson disease-associated neuronal death have been put forward in the brain, including oxidative stress and mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP to monkeys elicits the appearance of a parkinsonian syndrome, including morphological and functional impairments in the retina. However, the intracellular events leading to derangement of dopaminergic and other retinal neurons in MPTP-treated animal models have not been so far investigated. Here we have used a comparative proteomics approach to identify proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labelled separately with two different cyanine fluorophores and run pairwise on 2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to exhibit statistically significant differences in their expression levels, of at least ± 1.4-fold, in the parkinsonian monkey retina compared with controls. Most of these spots were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for protein sequence database interrogation, and 15 different proteins were successfully identified, of which 13 were underexpressed and 2 overexpressed. These proteins were involved in key cellular functional pathways such as glycolysis and mitochondrial electron transport, neuronal protection against stress and survival, and phototransduction processes. These functional categories underscore that alterations in energy metabolism, neuroprotective mechanisms and signal transduction are involved in MPTP-induced neuronal degeneration in the retina, in similarity to

Two-Photon Autofluorescence Imaging Reveals Cellular Structures Throughout the Retina of the Living Primate Eye.

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Sharma, Robin; Williams, David R; Palczewska, Grazyna; Palczewski, Krzysztof; Hunter, Jennifer J

2016-02-01

Although extrinsic fluorophores can be introduced to label specific cell types in the retina, endogenous fluorophores, such as NAD(P)H, FAD, collagen, and others, are present in all retinal layers. These molecules are a potential source of optical contrast and can enable noninvasive visualization of all cellular layers. We used a two-photon fluorescence adaptive optics scanning light ophthalmoscope (TPF-AOSLO) to explore the native autofluorescence of various cell classes spanning several layers in the unlabeled retina of a living primate eye. Three macaques were imaged on separate occasions using a custom TPF-AOSLO. Two-photon fluorescence was evoked by pulsed light at 730 and 920 nm excitation wavelengths, while fluorescence emission was collected in the visible range from several retinal layers and different locations. Backscattered light was recorded simultaneously in confocal modality and images were postprocessed to remove eye motion. All retinal layers yielded two-photon signals and the heterogeneous distribution of fluorophores provided optical contrast. Several structural features were observed, such as autofluorescence from vessel walls, Müller cell processes in the nerve fibers, mosaics of cells in the ganglion cell and other nuclear layers of the inner retina, as well as photoreceptor and RPE layers in the outer retina. This in vivo survey of two-photon autofluorescence throughout the primate retina demonstrates a wider variety of structural detail in the living eye than is available through conventional imaging methods, and broadens the use of two-photon imaging of normal and diseased eyes.

Effect of high-intensity irradiation from dental photopolymerization on the isolated and superfused vertebrate retina.

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Rassaei, Mohammad; Thelen, Martin; Abumuaileq, Ramzi; Hescheler, Jürgen; Lüke, Matthias; Schneider, Toni

2013-03-01

Light or electromagnetic radiation may damage the neurosensory retina during irradiation of photopolymerizing resinous materials. Direct and indirect effects of irradiation emitted from polymerisation curing light may represent a severe risk factor for the eyes and the skin of the lamp operators, as well as for the patient's oral mucosa. Bovine superfused retinas were used to record their light-evoked electroretinogram (ERG) as ex vivo ERGs. Both the a- and the b-waves were used as indicators for retinal damage on the functional level. The isolated retinas were routinely superfused with a standard nutrient solution under normoglycemic conditions (5 mM D-glucose). The change in the a- and b-wave amplitude and implicit time, caused by low and high intensity irradiation, was calculated and followed over time. From the results, it can be deduced that the irradiation from LED high-power lamps affects severely the normal physiological function of the bovine retina. Irradiations of 1,200 lx irreversibly damaged the physiological response. In part, this may be reversible at lower intensities, but curing without using the appropriate filter will bleach the retinal rhodopsin to a large extent within 20 to 40 s of standard application times. Constant exposure to intense ambient irradiation affects phototransduction (a-wave) as well as transretinal signalling. The proper use of the UV- and blue-light filtering device is highly recommended, and may prevent acute and long lasting damage of the neurosensory retina.

Avian cone photoreceptors tile the retina as five independent, self-organizing mosaics.

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Yoseph A Kram

2010-02-01

Full Text Available The avian retina possesses one of the most sophisticated cone photoreceptor systems among vertebrates. Birds have five types of cones including four single cones, which support tetrachromatic color vision and a double cone, which is thought to mediate achromatic motion perception. Despite this richness, very little is known about the spatial organization of avian cones and its adaptive significance. Here we show that the five cone types of the chicken independently tile the retina as highly ordered mosaics with a characteristic spacing between cones of the same type. Measures of topological order indicate that double cones are more highly ordered than single cones, possibly reflecting their posited role in motion detection. Although cones show spacing interactions that are cell type-specific, all cone types use the same density-dependent yardstick to measure intercone distance. We propose a simple developmental model that can account for these observations. We also show that a single parameter, the global regularity index, defines the regularity of all five cone mosaics. Lastly, we demonstrate similar cone distributions in three additional avian species, suggesting that these patterning principles are universal among birds. Since regular photoreceptor spacing is critical for uniform sampling of visual space, the cone mosaics of the avian retina represent an elegant example of the emergence of adaptive global patterning secondary to simple local interactions between individual photoreceptors. Our results indicate that the evolutionary pressures that gave rise to the avian retina's various adaptations for enhanced color discrimination also acted to fine-tune its spatial sampling of color and luminance.

In vivo two-photon imaging of retina in rabbits and rats.

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Jayabalan, Gopal Swamy; Wu, Yi-Kai; Bille, Josef F; Kim, Samuel; Mao, Xiao Wen; Gimbel, Howard V; Rauser, Michael E; Fan, Joseph T

2018-01-01

The purpose of this study was to evaluate the retina using near-infrared (NIR) two-photon scanning laser ophthalmoscopy. New Zealand white rabbits, albino rats, and brown Norway rats were used in this study. An autofluorescence image of the retina, including the retinal cells and its associated vasculatures was obtained by a real-time scan using the ophthalmoscope. Furthermore, the retinal vessels, nerve fiber layers and the non-pigmented retina were recorded with two-photon fluorescein angiography (FA); and the choroidal vasculatures were recorded using two-photon indocyanine green angiography (ICGA). Two-photon ICGA was achieved by exciting a second singlet state at ∼398 nm. Simultaneous two-photon FA and two-photon ICGA were performed to characterize the retinal and choroidal vessels with a single injection. The minimum laser power threshold required to elicit two-photon fluorescence was determined. The two-photon ophthalmoscope could serve as a promising tool to detect and monitor the disease progression in animal models. Moreover, these high-resolution images of retinal and choroidal vessels can be acquired in a real-time scan with a single light source, requiring no additional filters for FA or ICGA. The combination of FA and ICGA using the two-photon ophthalmoscope will help researchers to characterize the retinal diseases in animal models, and also to classify the types (classic, occult or mixed) of choroidal neovascularization (CNV) in macular degeneration. Furthermore, the prototype can be adapted to image the retina of rodents and rabbits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heterogeneous transgene expression in the retinas of the TH-RFP, TH-Cre, TH-BAC-Cre and DAT-Cre mouse lines.

Science.gov (United States)

Vuong, H E; Pérez de Sevilla Müller, L; Hardi, C N; McMahon, D G; Brecha, N C

2015-10-29

Transgenic mouse lines are essential tools for understanding the connectivity, physiology and function of neuronal circuits, including those in the retina. This report compares transgene expression in the retina of a tyrosine hydroxylase (TH)-red fluorescent protein (RFP) mouse line with three catecholamine-related Cre recombinase mouse lines [TH-bacterial artificial chromosome (BAC)-, TH-, and dopamine transporter (DAT)-Cre] that were crossed with a ROSA26-tdTomato reporter line. Retinas were evaluated and immunostained with commonly used antibodies including those directed to TH, GABA and glycine to characterize the RFP or tdTomato fluorescent-labeled amacrine cells, and an antibody directed to RNA-binding protein with multiple splicing to identify ganglion cells. In TH-RFP retinas, types 1 and 2 dopamine (DA) amacrine cells were identified by their characteristic cellular morphology and type 1 DA cells by their expression of TH immunoreactivity. In the TH-BAC-, TH-, and DAT-tdTomato retinas, less than 1%, ∼ 6%, and 0%, respectively, of the fluorescent cells were the expected type 1 DA amacrine cells. Instead, in the TH-BAC-tdTomato retinas, fluorescently labeled AII amacrine cells were predominant, with some medium diameter ganglion cells. In TH-tdTomato retinas, fluorescence was in multiple neurochemical amacrine cell types, including four types of polyaxonal amacrine cells. In DAT-tdTomato retinas, fluorescence was in GABA immunoreactive amacrine cells, including two types of bistratified and two types of monostratified amacrine cells. Although each of the Cre lines was generated with the intent to specifically label DA cells, our findings show a cellular diversity in Cre expression in the adult retina and indicate the importance of careful characterization of transgene labeling patterns. These mouse lines with their distinctive cellular labeling patterns will be useful tools for future studies of retinal function and visual processing. Published by Elsevier

CHANGES IN NEUROTRANSMITTER GENE EXPRESSION IN THE AGING RETINA.

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To understand mechanisms of neurotoxicity in susceptible populations, we examined age-related changes in constitutive gene expression in the retinas of young (4mos), middle-aged (11 mos) and aged (23 mos) male Long Evans rats. Derived from a pouch of the forebrain during develop...

The effects of microwave radiation on rabbit's retina

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Mohammad R. Talebnejad

2018-03-01

Conclusions: Histopathologically, cell phone simulated MW irradiation had no significant detrimental effect on the retina. However, ciliary body congestion was observed in greater fraction of those who received higher MW doses. Although there was no significant difference between post-treatment mean ERG values, there were statistically non-significant trends toward greater changes in the MW irradiated eyes.

Morphological characterization and topographic analysis of multiple photoreceptor types in the retinae of mesopelagic hatchetfishes with tubular eyes

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Lauren Michelle Biagioni

2016-03-01

Full Text Available Marine hatchetfishes, Argyropelecus spp., are one of the 14 genera of mesopelagic teleosts, which possess tubular eyes. The tubular eyes are positioned dorsally on the head and consist of a main retina, which subtends a large dorsal binocular field, and an accessory retina, which subtends the lateral monocular visual field. The topographic distribution of photoreceptors in the retina of Argyropelecus sladeni, A. affinis and A. aculeatus was determined using a random, unbiased and systematic stereological approach, which consistently revealed a region of high density (area centralis in the central region of the main retina (up to a peak of 96,000 receptors per mm2 and a relatively homogeneous density of photoreceptors in the accessory retina (of approximately 20,000 receptors per mm2. The position of the area centralis in the main retina indicates this retinal region subserves greater spatial resolution in the centre of the dorsal binocular visual field. Light microscopy and transmission electron microscopy also revealed the presence of multiple photoreceptor types (two rod-like and one cone-like based on the size and shape of the inner and outer segments and ultrastructural differences in the ellipsoidal region. The presence of multiple photoreceptor types in these tubular-eyed, mesopelagic hatchetfishes may reflect the need for the visual system to function under different lighting conditions during vertical migratory behavior, especially given their unique dorsally-facing eyes.

Lattice degeneration of the retina.

Science.gov (United States)

Byer, N E

1979-01-01

Lattice degeneration of the retina is the most important of all clinically distinct entities that effect the peripheral fundus and are related to retinal detachment. The purpose of this review is to survey the extensive literature, to evaluate the many diverse opinions on this subject, and to correlate and summarize all the known facts regarding this disease entity. The disease is fully defined and described, both clinically and histologically. Some aspects of the disease are still poorly understood, and some remain controversial, especially in the area of management. For this reason, the indications for treatment are discussed under eight subsections, with a view toward providing practical guidelines for recommendations in management.

Potassium-stimulated release of radiolabelled taurine and glycine from the isolated rat retina

Energy Technology Data Exchange (ETDEWEB)

Smith, L.F.; Pycock, C.J.

1982-09-01

The release of preloaded (/sup 3/H)glycine and (/sup 3/H)taurine in response to a depolarising stimulus (12.5-50 mM KCl) has been studied in the superfused rat retina. High external potassium concentration immediately increased the spontaneous efflux of (/sup 3/H)glycine, the effect of 50 mM K+ apparently being abolished by omitting calcium from the superfusing medium. In contrast, although high potassium concentrations increased the spontaneous efflux of (/sup 3/H)taurine from the superfused rat retina, this release was not evident until the depolarising stimulus was removed from the superfusing medium. The magnitude of this late release of (/sup 3/H)taurine was dependent on external K+ concentrations, and appeared immediately after cessation of the stimulus irrespective of whether it was applied for 4, 8, or 12 min. Potassium (50 mM)-induced release of taurine appeared partially calcium-dependent, being significantly reduced (p less than 0.01) but not abolished by replacing calcium with 1 mM EDTA in the superfusate. High-affinity uptake systems for both (/sup 3/H)glycine and (/sup 3/H)taurine were demonstrated in the rat retina in vitro (Km values, 1.67 microM and 2.97 microM; Vmax values, 19.3 and 23.1 nmol/g wet weight tissue/h, respectively). The results are discussed with respect to the possible neurotransmitter roles of both amino acids in the rat retina.

Sustainability and Counteracting Factors to Profit Rate Decline

DEFF Research Database (Denmark)

Ougaard, Morten

2014-01-01

This paper discusses sustainability implications of barriers to growth as specified in the theory of the long-term falling rate of profit but focusing on the counteracting factors (CFs) specified by Marx. These depend much on political processes and are important in state theory for understanding...... policies of national and international institutions. Fourteen partly overlapping factors are identified and grouped in five categories: increased pressure on labor, geographical expansion, resource efficiency, technological progress, and destruction or devaluation of capital. It is suggested...

Diagnostic classification of retinal degenerative diseases São Paulo and Vale Retina groups

OpenAIRE

Unonius, Nichard; Farah, Michel Eid; Sallum, Juliana M. Ferraz

2003-01-01

OBJETIVO:Organizar um banco de dados regional de todos os indivíduos portadores de doenças degenerativas da retina, com o objetivo de classificar cada paciente de acordo com o tipo de distrofia e padrão de herança. MÉTODOS: Durante o encontro do Grupo Retina São Paulo no dia 5 de maio de 2001, duzentas e quarenta e três pessoas foram registradas, sendo que parte forneceu dados de antecedentes oculares, pessoais e familiares e árvore genealógica. Noventa e três pacientes foram questionados qua...

Eye Controlled Simulation of Scotoma Effects on the Retina

Science.gov (United States)

1990-07-01

movements since the central region of the viewing. The PRLs were positioned near the retina, the macula , and its center, the fovea, have scotoma boundary...scotoma area; as macular degeneration increases in size. near to the fovea as possible to maximize acuity, Feedback of failures to detect targets might

Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.

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Laurence Meyer

Full Text Available Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in

Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq

Science.gov (United States)

Whitmore, S. Scott; Wagner, Alex H.; DeLuca, Adam P.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Zeng, Shemin; Braun, Terry A.; Mullins, Robert F.; Scheetz, Todd E.

2014-01-01

Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell-types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq.

Science.gov (United States)

Whitmore, S Scott; Wagner, Alex H; DeLuca, Adam P; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Zeng, Shemin; Braun, Terry A; Mullins, Robert F; Scheetz, Todd E

2014-12-01

Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

Photonic crystal light collectors in fish retina improve vision in turbid water.

Science.gov (United States)

Kreysing, Moritz; Pusch, Roland; Haverkate, Dorothee; Landsberger, Meik; Engelmann, Jacob; Ruiter, Janina; Mora-Ferrer, Carlos; Ulbricht, Elke; Grosche, Jens; Franze, Kristian; Streif, Stefan; Schumacher, Sarah; Makarov, Felix; Kacza, Johannes; Guck, Jochen; Wolburg, Hartwig; Bowmaker, James K; von der Emde, Gerhard; Schuster, Stefan; Wagner, Hans-Joachim; Reichenbach, Andreas; Francke, Mike

2012-06-29

Despite their diversity, vertebrate retinae are specialized to maximize either photon catch or visual acuity. Here, we describe a functional type that is optimized for neither purpose. In the retina of the elephantnose fish (Gnathonemus petersii), cone photoreceptors are grouped together within reflecting, photonic crystal-lined cups acting as macroreceptors, but rod photoreceptors are positioned behind these reflectors. This unusual arrangement matches rod and cone sensitivity for detecting color-mixed stimuli, whereas the photoreceptor grouping renders the fish insensitive to spatial noise; together, this enables more reliable flight reactions in the fish's dim and turbid habitat as compared with fish lacking this retinal specialization.

Utilization of glutamine by the retina: an autoradiographic and metabolic study

Energy Technology Data Exchange (ETDEWEB)

Voaden, M J; Lake, N; Marshall, J; Morjaria, B [Institute of Ophthalmology, London (UK). Dept. of Visual Science

1978-10-01

The cells able to accumulate exogenously applied (/sup 3/H) glutamine in rat, cat, frog, pigeon and guinea pig retinas have been located by autoradiography, and the fate of the labelled glutamine, as regards its incorporation into aspartic, glutamic and ..gamma..-amino-butyric acids, followed for 60 min. The results support the notion of glutamine as a precursor of transmitter amino acids in some neurones. In particular, it would appear to be a source of a relatively stable pool of GABA which may be located, with species variation, in amacrine or ganglion cells. In the pigeon retina glutamate pool incorporates and retains a major percentage of the label, and perikarya in the middle of the inner nuclear layer of the tissue are predominantly labelled.

Local edge detectors: a substrate for fine spatial vision at low temporal frequencies in rabbit retina.

Science.gov (United States)

van Wyk, Michiel; Taylor, W Rowland; Vaney, David I

2006-12-20

Visual acuity is limited by the size and density of the smallest retinal ganglion cells, which correspond to the midget ganglion cells in primate retina and the beta-ganglion cells in cat retina, both of which have concentric receptive fields that respond at either light-On or light-Off. In contrast, the smallest ganglion cells in the rabbit retina are the local edge detectors (LEDs), which respond to spot illumination at both light-On and light-Off. However, the LEDs do not predominate in the rabbit retina and the question arises, what role do they play in fine spatial vision? We studied the morphology and physiology of LEDs in the isolated rabbit retina and examined how their response properties are shaped by the excitatory and inhibitory inputs. Although the LEDs comprise only approximately 15% of the ganglion cells, neighboring LEDs are separated by 30-40 microm on the visual streak, which is sufficient to account for the grating acuity of the rabbit. The spatial and temporal receptive-field properties of LEDs are generated by distinct inhibitory mechanisms. The strong inhibitory surround acts presynaptically to suppress both the excitation and the inhibition elicited by center stimulation. The temporal properties, characterized by sluggish onset, sustained firing, and low bandwidth, are mediated by the temporal properties of the bipolar cells and by postsynaptic interactions between the excitatory and inhibitory inputs. We propose that the LEDs signal fine spatial detail during visual fixation, when high temporal frequencies are minimal.

Flash photolysis of rhodopsin in the cat retina

International Nuclear Information System (INIS)

Ripps, H.; Mehaffey, L.; Siegel, I.M.; Ernst, W.; Kemp, C.M.

1981-01-01

The bleaching of rhodopsin by short-duration flashes of a xenon discharge lamp was studied in vivo in the cat retina with the aid of a rapid, spectral-scan fundus reflectometer. Difference spectra recorded over a broad range of intensities showed that the bleaching efficacy of high-intensity flashes was less than that of longer duration, steady lights delivering the same amount of energy. Both the empirical results and those derived from a theoretical analysis of flash photolysis indicate that, under the conditions of these experiments, the upper limit of the flash bleaching of rhodopsin in cat is approximately 90%. Although the fact that a full bleach could not be attained is attributable to photoreversal, i.e., the photic regeneration of rhodopsin from its light-sensitive intermediates, the 90% limit is considerably higher than the 50% (or lower) value obtained under other experimental circumstances. Thus, it appears that the duration (approximately 1 ms) and spectral composition of the flash, coupled with the kinetic parameters of the thermal and photic reactions in the cat retina, reduce the light-induced regeneration of rhodopsin to approximately 10%

STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF BENIGN FLECK RETINA USING MULTIMODAL IMAGING.

Science.gov (United States)

Neriyanuri, Srividya; Rao, Chetan; Raman, Rajiv

2017-01-01

To report structural and functional features in a case series of benign fleck retina using multimodal imaging. Four cases with benign fleck retina underwent complete ophthalmic examination that included detailed history, visual acuity, and refractive error testing, FM-100 hue test, dilated fundus evaluation, full field electroretinogram, fundus photography with autofluorescence, fundus fluorescein angiography, and swept-source optical coherence tomography. Age group of the cases ranged from 19 years to 35 years (3 males and 1 female). Parental consanguinity was reported in two cases. All of them were visually asymptomatic with best-corrected visual acuity of 20/20 (moderate astigmatism) in both the eyes. Low color discrimination was seen in two cases. Fundus photography showed pisciform flecks which were compactly placed on posterior pole and were discrete, diverging towards periphery. Lesions were seen as smaller dots within 1500 microns from fovea and were hyperfluorescent on autofluorescence. Palisading retinal pigment epithelium defects were seen in posterior pole on fundus fluorescein angiography imaging; irregular hyper fluorescence was also noted. One case had reduced cone responses on full field electroretinogram; the other three cases had normal electroretinogram. On optical coherence tomography, level of lesions varied from retinal pigment epithelium, inner segment to outer segment extending till external limiting membrane. Functional and structural deficits in benign fleck retina were picked up using multimodal imaging.

Heidelberg Retina Tomograph for the Detection of Glaucoma

Directory of Open Access Journals (Sweden)

Barbara Cvenkel

2012-06-01

Full Text Available Heidelberg Retina Tomograph (HRT is a confocal scanning laser ophthalmoscope which acquires and analyzes 3-dimensional images of the optic nerve head. The latest instrument HRT3 includes software with larger ethinic-specific normative database. This review summarizes relevant published literature on HRT in diagnosing glaucoma, detecting glaucoma progression, the diagnostic accuracy of HRT among other imaging devices and its role in clinical practice.

Neural signal for counteracting pre-action bias in the centromedian thalamic nucleus

Directory of Open Access Journals (Sweden)

Takafumi eMinamimoto

2014-01-01

Full Text Available Most of our daily actions are selected and executed involuntarily under familiar situations by the guidance of internal drives, such as motivation. The behavioral tendency or biasing towards one over others reflects the action-selection process in advance of action execution (i.e., pre-action bias. Facing unexpected situations, however, pre-action bias should be withdrawn and replaced by an alternative that is suitable for the situation (i.e., counteracting bias. To understand the neural mechanism for the counteracting process, we studied the neural activity of the thalamic centromedian (CM nucleus in monkeys performing GO-NOGO task with asymmetrical or symmetrical reward conditions. The monkeys reacted to GO signal faster in large-reward condition, indicating behavioral bias toward large reward. In contrast, they responded slowly in small-reward condition, suggesting a conflict between internal drive and external demand. We found that neurons in the CM nucleus exhibited phasic burst discharges after GO and NOGO instructions especially when they were associated with small reward. The small-reward preference was positively correlated with the strength of behavioral bias toward large reward. The small-reward preference disappeared when only NOGO action was requested. The timing of activation predicted the timing of action opposed to bias. These results suggest that CM signals the discrepancy between internal pre-action bias and external demand, and mediates the counteracting process — resetting behavioral bias and leading to execution of opposing action.

Retina Image Analysis and Ocular Telehealth: The Oak Ridge National Laboratory-Hamilton Eye Institute Case Study

Energy Technology Data Exchange (ETDEWEB)

Karnowski, Thomas Paul [ORNL; Giancardo, Luca [ORNL; Li, Yaquin [University of Tennessee, Knoxville (UTK); Tobin Jr, Kenneth William [ORNL; Chaum, Edward [University of Tennessee, Knoxville (UTK)

2013-01-01

Automated retina image analysis has reached a high level of maturity in recent years, and thus the question of how validation is performed in these systems is beginning to grow in importance. One application of retina image analysis is in telemedicine, where an automated system could enable the automated detection of diabetic retinopathy and other eye diseases as a low-cost method for broad-based screening. In this work we discuss our experiences in developing a telemedical network for retina image analysis, including our progression from a manual diagnosis network to a more fully automated one. We pay special attention to how validations of our algorithm steps are performed, both using data from the telemedicine network and other public databases.

Infrared reflectance as a diagnostic adjunct for subclinical commotio retinae

Directory of Open Access Journals (Sweden)

Nicholas H Andrew

2014-01-01

Full Text Available Commotio retinae (CR is an outer retinal disorder following blunt trauma to the eye. Histologically it is characterized by disruption of the photoreceptor outer segments (OS, typically without injury to other retinal layers. Using spectral-domain optical coherence tomography (OCT the condition is visible as hyper-reflectivity of the OS. Most cases of CR are associated with transient grey-white discoloration of the retina and are easily diagnosed clinically, but there have been reports of OCT-confirmed CR without retinal discoloration. It is likely that this subclinical variant of CR is under-recognized as the OCT features of CR are subtle. Here, we report a case of OCT-confirmed subclinical CR that demonstrated prominent infrared hypo-reflectance, using the infrared protocol of the SPECTRALIS® OCT, Heidelberg Engineering. This case suggests that infrared reflectance may have a role in diagnosing cases of subclinical CR.

Counteracting the Influence of Peer Smoking on YouTube

OpenAIRE

Romer, Daniel; Jamieson, Patrick E.; Jamieson, Kathleen Hall; Jones, Christopher; Sherr, Susan

2017-01-01

YouTube, a popular online site for user-generated content, is emerging as a powerful source of peer modeling of smoking. Previous research suggests that in counteracting such influence, health messages may inadvertently increase the perceived prevalence of drug use (a descriptive norm) without reducing its acceptability (injunctive norm). This research tested the ability of health messages to reduce the social acceptability of peer smoking on YouTube despite enhancing its perceived prevalence...

PGC-1α determines light damage susceptibility of the murine retina.

Directory of Open Access Journals (Sweden)

Anna Egger

Full Text Available The peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1 proteins are key regulators of cellular bioenergetics and are accordingly expressed in tissues with a high energetic demand. For example, PGC-1α and PGC-1β control organ function of brown adipose tissue, heart, brain, liver and skeletal muscle. Surprisingly, despite their prominent role in the control of mitochondrial biogenesis and oxidative metabolism, expression and function of the PGC-1 coactivators in the retina, an organ with one of the highest energy demands per tissue weight, are completely unknown. Moreover, the molecular mechanisms that coordinate energy production with repair processes in the damaged retina remain enigmatic. In the present study, we thus investigated the expression and function of the PGC-1 coactivators in the healthy and the damaged retina. We show that PGC-1α and PGC-1β are found at high levels in different structures of the mouse retina, most prominently in the photoreceptors. Furthermore, PGC-1α knockout mice suffer from a striking deterioration in retinal morphology and function upon detrimental light exposure. Gene expression studies revealed dysregulation of all major pathways involved in retinal damage and apoptosis, repair and renewal in the PGC-1α knockouts. The light-induced increase in apoptosis in vivo in the absence of PGC-1α was substantiated in vitro, where overexpression of PGC-1α evoked strong anti-apoptotic effects. Finally, we found that retinal levels of PGC-1 expression are reduced in different mouse models for retinitis pigmentosa. We demonstrate that PGC-1α is a central coordinator of energy production and, importantly, all of the major processes involved in retinal damage and subsequent repair. Together with the observed dysregulation of PGC-1α and PGC-1β in retinitis pigmentosa mouse models, these findings thus imply that PGC-1α might be an attractive target for therapeutic approaches aimed at retinal

Functional characterization of rs2229094 (T>C polymorphism in the tumor necrosis factor locus and lymphotoxin alpha expression in human retina: the Retina 4 project

Directory of Open Access Journals (Sweden)

Pastor-Idoate S

2017-05-01

Full Text Available Salvador Pastor-Idoate,1,2 Irene Rodríguez-Hernández,2,3 Jimena Rojas,1 Lucia Gonzalez-Buendia,1 Santiago Delgado-Tirado,1,4 Jose Carlos López,1 Rogelio González-Sarmiento,2,3 Jose C Pastor1,4 1IOBA Eye Institute, University of Valladolid, Valladolid, 2Molecular Medicine Unit, Department of Medicine, 3Molecular and Cellular Cancer Biology Institute, High Council of Scientific Research, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, 4Department of Ophthalmology, Hospital Clínico Universitario, Valladolid, Spain Purpose: The objective of this study is to determine the expression and localization of lymphotoxin alpha (LTA in human retinas and the functionality of one of its polymorphisms rs2229094 (C13R (T>C, previously associated with proliferative vitreoretinopathy (PVR development.Materials and methods: Total RNA from three healthy human retinas were extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR analysis, using flanking primers of LTA cDNA. In addition, three human eyes with retinal detachment (RD and three healthy control eyes were subjected to immunohistochemistry (IHC with a specific antibody against LTA. The functionality of T and C alleles was assessed by using pCEFL-Flag expression vector and transient transfection assays in COS-1 cell line. In addition, expression analysis by RT-PCR, Western blot and subcellular localization of both alleles and by immunofluorescence assay was performed.Results: RT-PCR analysis revealed no significant levels of messenger RNA (mRNA LTA in healthy human retinas. Sequential IHC staining showed differences between healthy human and RD retinas. No differences in mRNA and protein expression levels and in subcellular localization between both alleles were found. Both alleles were located in the cytoplasm of COS-1 cells.Conclusion: Although results suggest lack of functionality, the differences found in IHC study and its strong association

Heparin-Binding EGF-like Growth Factor (HB-EGF) stimulates the proliferation of Müller glia-derived progenitor cells in avian and murine retinas

Science.gov (United States)

Todd, Levi; Volkov, Leo I.; Zelinka, Chris; Squires, Natalie; Fischer, Andy J.

2015-01-01

Müller glia can be stimulated to de-differentiate, proliferate and form Müller glia-derived progenitor cells (MGPCs) that regenerate retinal neurons. In the zebrafish retina, Heparin-Binding EGF-like Growth Factor (HB-EGF) may be one of the key factors that stimulate the formation of proliferating MGPCs. Currently nothing is known about the influence of HB-EGF on the proliferative potential of Müller glia in retinas of birds and rodents. In the chick retina, we found that levels of both hb-egf and egf-receptor are rapidly and transiently up-regulated following NMDA-induced damage. Although intraocular injections of HB-EGF failed to stimulate cell-signaling or proliferation of Müller glia in normal retinas, HB-EGF stimulated proliferation of MGPCs in damaged retinas. By comparison, inhibition of the EGF-receptor (EGFR) decreased the proliferation of MGPCs in damaged retinas. HB-EGF failed to act synergistically with FGF2 to stimulate the formation of MGPCs in the undamaged retina and inhibition of EGF-receptor did not suppress FGF2-mediated formation of MGPCs. In the mouse retina, HB-EGF stimulated the proliferation of Müller glia following NMDA-induced damage. Furthermore, HB-EGF stimulated not only MAPK-signaling in Müller glia/MGPCs, but also activated mTor- and Jak/Stat-signaling. We propose that levels of expression of EGFR are rate-limiting to the responses of Müller glia to HB-EGF and the expression of EGFR can be induced by retinal damage, but not by FGF2-treatment. We conclude that HB-EGF is mitogenic to Müller glia in both chick and mouse retinas, and HB-EGF is an important player in the formation of MGPCs in damaged retinas. PMID:26500021

3D finite element modeling of epiretinal stimulation: Impact of prosthetic electrode size and distance from the retina.

Science.gov (United States)

Sui, Xiaohong; Huang, Yu; Feng, Fuchen; Huang, Chenhui; Chan, Leanne Lai Hang; Wang, Guoxing

2015-05-01

A novel 3-dimensional (3D) finite element model was established to systematically investigate the impact of the diameter (Φ) of disc electrodes and the electrode-to-retina distance on the effectiveness of stimulation. The 3D finite element model was established based on a disc platinum stimulating electrode and a 6-layered retinal structure. The ground electrode was placed in the extraocular space in direct attachment with sclera and treated as a distant return electrode. An established criterion of electric-field strength of 1000 Vm-1 was adopted as the activation threshold for RGCs. The threshold current (TC) increased linearly with increasing Φ and electrode-to-retina distance and remained almost unchanged with further increases in diameter. However, the threshold charge density (TCD) increased dramatically with decreasing electrode diameter. TCD exceeded the electrode safety limit for an electrode diameter of 50 µm at an electrode-to-retina distance of 50 to 200 μm. The electric field distributions illustrated that smaller electrode diameters and shorter electrode-to-retina distances were preferred due to more localized excitation of RGC area under stimulation of different threshold currents in terms of varied electrode size and electrode-to-retina distances. Under the condition of same-amplitude current stimulation, a large electrode exhibited an improved potential spatial selectivity at large electrode-to-retina distances. Modeling results were consistent with those reported in animal electrophysiological experiments and clinical trials, validating the 3D finite element model of epiretinal stimulation. The computational model proved to be useful in optimizing the design of an epiretinal stimulating electrode for prosthesis.

Counteracting loneliness: on the restorative function of nostalgia.

Science.gov (United States)

Zhou, Xinyue; Sedikides, Constantine; Wildschut, Tim; Gao, Ding-Guo

2008-10-01

Four studies tested whether nostalgia can counteract reductions in perceived social support caused by loneliness. Loneliness reduced perceptions of social support but increased nostalgia. Nostalgia, in turn, increased perceptions of social support. Thus, loneliness affected perceived social support in two distinct ways. Whereas the direct effect of loneliness was to reduce perceived social support, the indirect effect of loneliness was to increase perceived social support via nostalgia. This restorative function of nostalgia was particularly apparent among resilient persons. Nostalgia is a psychological resource that protects and fosters mental health.

Simultaneous optical coherence tomography and lipofuscin autofluorescence imaging of the retina with a single broadband light source at 480nm

OpenAIRE

Jiang, Minshan; Liu, Tan; Liu, Xiaojing; Jiao, Shuliang

2014-01-01

We accomplished spectral domain optical coherence tomography and auto-fluorescence microscopy for imaging the retina with a single broadband light source centered at 480 nm. This technique is able to provide simultaneous structural imaging and lipofuscin molecular contrast of the retina. Since the two imaging modalities are provided by the same group of photons, their images are intrinsically registered. To test the capabilities of the technique we periodically imaged the retinas of the same ...

[VEGF expression in dog retina after chorioretinal venous anastomosis].

Science.gov (United States)

Lu, Ning; Li, Zhihui; Sun, Xianli; Wang, Guanglu; Zhang, Feng; Peng, Xiaoyan

2002-09-01

To identify changes in vascular endothelial growth factor (VEGF) expression in the dog retina after laser-induced chorioretinal venous anastomosis (CRVA), in order to find out the relationship between CRVA treatment and the related neovascular complications. Immediately after branch retinal vein occlusion (BRVO) model was made in 5 eyes of 5 normal dogs, CRVA treatment was done over a small tributary vein in the drainage distribution of the occluded vein. In each eye, there were 2 - 3 treatment sites. Four to six weeks later, a repeated treatment was given if the first treatment failed to show the anastomosis. The treatment sites with successful CRVA were divided into two groups: the small laser spot group, which received one treatment and the big laser spot group, which received more than one treatment. The expression of VEGF was investigated immunohistochemically in the treatment sites with successful anastomoses and in the 5 normal fellow eyes (control). There were totally 10 successful anastomoses in the 5 experimental eyes, among which, five received one treatment and the other 5 received more than one treatment. On fundus examination, the small laser spots were round and small, and the big laser spots were large with local proliferation. VEGF immunoreactivity was absent/weak in the normal dog retina, and remained unchanged in the small laser spot group, but somewhat increased in the big laser spot group. No neovascular complications occurred. All immunostaining experiments were accompanied by proper controls and none of the negative controls showed any immunoreactivity. Proper laser treatment can induce CRVA quite safely in nonischemic dog retina, which does not cause changes in the expression of VEGF, but severe laser damage in the treatment site can cause increased VEGF expression which may be related to neovascular complications.

Simulated human eye retina adaptive optics imaging system based on a liquid crystal on silicon device

International Nuclear Information System (INIS)

Jiang Baoguang; Cao Zhaoliang; Mu Quanquan; Hu Lifa; Li Chao; Xuan Li

2008-01-01

In order to obtain a clear image of the retina of model eye, an adaptive optics system used to correct the wave-front error is introduced in this paper. The spatial light modulator that we use here is a liquid crystal on a silicon device instead of a conversional deformable mirror. A paper with carbon granule is used to simulate the retina of human eye. The pupil size of the model eye is adjustable (3-7 mm). A Shack–Hartman wave-front sensor is used to detect the wave-front aberration. With this construction, a value of peak-to-valley is achieved to be 0.086 λ, where λ is wavelength. The modulation transfer functions before and after corrections are compared. And the resolution of this system after correction (691p/m) is very close to the dirraction limit resolution. The carbon granule on the white paper which has a size of 4.7 μm is seen clearly. The size of the retina cell is between 4 and 10 mu;m. So this system has an ability to image the human eye's retina. (classical areas of phenomenology)

Segmentasi Pembuluh Darah Retina Pada Citra Fundus Menggunakan Gradient Based Adaptive Thresholding Dan Region Growing

Directory of Open Access Journals (Sweden)

Deni Sutaji

2016-07-01

Full Text Available AbstrakSegmentasi pembuluh darah pada citra fundus retina menjadi hal yang substansial dalam dunia kedokteran, karena dapat digunakan untuk mendeteksi penyakit, seperti: diabetic retinopathy, hypertension, dan cardiovascular. Dokter membutuhkan waktu sekitar dua jam untuk mendeteksi pembuluh darah retina, sehingga diperlukan metode yang dapat membantu screening agar lebih cepat.Penelitian sebelumnya mampu melakukan segmentasi pembuluh darah yang sensitif terhadap variasi ukuran lebar pembuluh darah namun masih terjadi over-segmentasi pada area patologi. Oleh karena itu, penelitian ini bertujuan untuk mengembangkan metode segmentasi pembuluh darah pada citra fundus retina yang dapat mengurangi over-segmentasi pada area patologi menggunakan Gradient Based Adaptive Thresholding dan Region Growing.Metode yang diusulkan terdiri dari 3 tahap, yaitu segmentasi pembuluh darah utama, deteksi area patologi dan segmentasi pembuluh darah tipis. Tahap segmentasi pembuluh darah utama menggunakan high-pass filtering dan tophat reconstruction pada kanal hijau citra yang sudah diperbaiki kontrasnya sehingga lebih jelas perbedaan antara pembuluh darah dan background. Tahap deteksi area patologi menggunakan metode Gradient Based Adaptive Thresholding. Tahap segmentasi pembuluh darah tipis menggunakan Region Growing berdasarkan informasi label pembuluh darah utama dan label area patologi. Hasil segmentasi pembuluh darah utama dan pembuluh darah tipis kemudian digabungkan sehingga menjadi keluaran sistem berupa citra biner pembuluh darah. Berdasarkan hasil uji coba, metode ini mampu melakukan segmentasi pembuluh darah retina dengan baik pada citra fundus DRIVE, yaitu dengan akurasi rata-rata 95.25% dan nilai Area Under Curve (AUC pada kurva Relative Operating Characteristic (ROC sebesar 74.28%.                           Kata Kunci: citra fundus retina, gradient based adaptive thresholding, patologi, pembuluh darah retina, region growing

Adaptive Optical System for Retina Imaging Approaches Clinic Applications

Science.gov (United States)

Ling, N.; Zhang, Y.; Rao, X.; Wang, C.; Hu, Y.; Jiang, W.; Jiang, C.

We presented "A small adaptive optical system on table for human retinal imaging" at the 3rd Workshop on Adaptive Optics for Industry and Medicine. In this system, a 19 element small deformable mirror was used as wavefront correction element. High resolution images of photo receptors and capillaries of human retina were obtained. In recent two years, at the base of this system a new adaptive optical system for human retina imaging has been developed. The wavefront correction element is a newly developed 37 element deformable mirror. Some modifications have been adopted for easy operation. Experiments for different imaging wavelengths and axial positions were conducted. Mosaic pictures of photoreceptors and capillaries were obtained. 100 normal and abnormal eyes of different ages have been inspected.The first report in the world concerning the most detailed capillary distribution images cover ±3° by ± 3° field around the fovea has been demonstrated. Some preliminary very early diagnosis experiment has been tried in laboratory. This system is being planned to move to the hospital for clinic experiments.

Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina.

Directory of Open Access Journals (Sweden)

Tracy Ho

Full Text Available Amyloid precursor protein (APP is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry.

GABA sensitivity of spectrally classified horizontal cells in goldfish retina

NARCIS (Netherlands)

Verweij, J.; Kamermans, M.; Negishi, K.; Spekreijse, H.

1998-01-01

We studied the GABA sensitivity of horizontal cells in the isolated goldfish retina. After the glutamatergic input to the horizontal cells was blocked with DNQX, GABA depolarized the monophasic and biphasic horizontal cells. The pharmacology of these GABA-induced depolarizations was tested with the

Evaluation of the central macula in commotio retinae not associated with other types of traumatic retinopathy.

Science.gov (United States)

Park, Joo Youn; Nam, Woo Ho; Kim, Seung Hoon; Jang, Sun Young; Ohn, Young-Hoon; Park, Tae Kwann

2011-08-01

To report on the anatomical and functional changes to the macula in nine patients suffering from commotio retinae not accompanied by any other types of traumatic retinopathy. Nine injured eyes with commotio retinae were evaluated soon after ocular trauma with ophthalmic examination, including Spectral-domain optical coherence tomography (SD-OCT). In 12 eyes of 6 patients, Humphrey visual field (HVF) and multifocal electroretinogram (mfERG) were performed. Re-examinations were periodically performed for a mean of 26 days. Data from 9 injured eyes were collected and compared to data collected from the 9 non-affected eyes of the same patients. SD-OCT revealed no significant differences in the foveal thickness and total macular volume between traumatized and intact eyes in all 9 patients. Only 3 out of the 9 injured eyes showed abnormal findings in SD-OCT images such as discontinuity of the inner/outer segment (IS/OS) junction or abnormal hyper-reflectivity from the IS/OS and retinal pigment epithelium (RPE) lines in the macula. HVF and mfERG results did not show any functional deterioration in the injured eyes compared with intact eyes. During follow-up, the commotio retinae resolved in all 9 eyes. The changes to the outer retinal region detected in 3 patients by SD-OCT were also resolved. Acute retinal changes in commotio retinae, not associated with other retinal pathologies, were resolved without histological and functional sequelae. In a few cases of commotio retinae, SD-OCT revealed transient abnormalities mainly observed at the IS/OS and RPE complexes.

Administrative-legal regulation of causes and conditions determining corruption in social sphere

Directory of Open Access Journals (Sweden)

Aleksandr V. Polukarov

2017-12-01

Full Text Available Objective to show the capabilities of administrativelegal regulation for combating the causes and conditions determining corrupt behavior in the social sphere. Methods dialectic approach to cognition of social phenomena enabling to analyze them in historical development and functioning in the context of the totality of objective and subjective factors that determined the choice of the following research methods analysis synthesis comparison systematic formallegal comparativelegal methods. Results the reasons and conditions determining the corruption in the social sphere were disclosed this leads to the conclusion that corruption counteraction should be based on 1 recognition of the social sphere as the key object of protection against corruption 2 elaboration of special administrativelegal means of corruption counteraction in the social sphere. It is necessary to take into account the features of social relations in such sectors as education healthcare culture physical culture and sports etc. A number of foreign countries took the path of developing legislation on corruption counteraction taking into account the specifics of various social sphere segments functioning. This experience is quite interesting from the viewpoint of developing means of combating the causes and conditions that determine corruption in the social sphere. A number of the Russian Federation subjects also elaborate regional programs of combating corruption in education healthcare and culture. In our opinion this experience should be transferred to the federal level of legal regulation. This will help to create a fullfledged system of corruption counteraction in the social sphere taking into account different levels of its functioning. Scientific novelty for the first time in administrativelegal science the ldquolaw of torts aspect of corruption in the social sphererdquo issue is considered the work reveals the causes and conditions that determine corruption in the social

Quantitative analysis of retina layer elasticity based on automatic 3D segmentation (Conference Presentation)

Science.gov (United States)

He, Youmin; Qu, Yueqiao; Zhang, Yi; Ma, Teng; Zhu, Jiang; Miao, Yusi; Humayun, Mark; Zhou, Qifa; Chen, Zhongping

2017-02-01

Age-related macular degeneration (AMD) is an eye condition that is considered to be one of the leading causes of blindness among people over 50. Recent studies suggest that the mechanical properties in retina layers are affected during the early onset of disease. Therefore, it is necessary to identify such changes in the individual layers of the retina so as to provide useful information for disease diagnosis. In this study, we propose using an acoustic radiation force optical coherence elastography (ARF-OCE) system to dynamically excite the porcine retina and detect the vibrational displacement with phase resolved Doppler optical coherence tomography. Due to the vibrational mechanism of the tissue response, the image quality is compromised during elastogram acquisition. In order to properly analyze the images, all signals, including the trigger and control signals for excitation, as well as detection and scanning signals, are synchronized within the OCE software and are kept consistent between frames, making it possible for easy phase unwrapping and elasticity analysis. In addition, a combination of segmentation algorithms is used to accommodate the compromised image quality. An automatic 3D segmentation method has been developed to isolate and measure the relative elasticity of every individual retinal layer. Two different segmentation schemes based on random walker and dynamic programming are implemented. The algorithm has been validated using a 3D region of the porcine retina, where individual layers have been isolated and analyzed using statistical methods. The errors compared to manual segmentation will be calculated.

Physical activity counteracts tumor cell growth in colon carcinoma C26-injected muscles: an interim report

Directory of Open Access Journals (Sweden)

Charlotte Hiroux

2016-06-01

Full Text Available Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis.

Human Neural Stem Cell Aging Is Counteracted by α-Glycerylphosphorylethanolamine.

Science.gov (United States)

Daniele, Simona; Da Pozzo, Eleonora; Iofrida, Caterina; Martini, Claudia

2016-07-20

Neural stem cells (NSCs) represent a subpopulation of cells, located in specific regions of the adult mammalian brain, with the ability of self-renewing and generating neurons and glia. In aged NSCs, modifications in the amount and composition of membrane proteins/lipids, which lead to a reduction in membrane fluidity and cholinergic activities, have been reported. In this respect, molecules that are effective at normalizing the membrane composition and cholinergic signaling could counteract stem cell aging. α-Glycerylphosphorylethanolamine (GPE), a nootropic drug, plays a role in phospholipid biosynthesis and acetylcholine release. Herein, GPE was assayed on human NSC cultures and on hydroxyurea-aged cells. Using cell counting, colorimetric, and fluorimetric analyses, immunoenzymatic assays, and real time PCR experiments, NSC culture proliferation, senescence, reactive oxygen species, and ADP/ATP levels were assessed. Aged NSCs exhibited cellular senescence, decreased proliferation, and an impairment in mitochondrial metabolism. These changes included a substantial induction in the nuclear factor NF-κB, a key inflammatory mediator. GPE cell treatment significantly protected the redox state and functional integrity of mitochondria, and counteracted senescence and NF-κB activation. In conclusion, our data show the beneficial properties of GPE in this model of stem cell aging.

Near UV radiation effect on the lens and retina

International Nuclear Information System (INIS)

Zigman, S.

1987-01-01

The discussion presented in this paper indicates that the retina of a diurnal animal with a natural UV-absorbing lens (ie: the gray squirrel) is susceptible to near-UV damage from environmental sources only after the lens has been removed. This suggests that it is very important to protect against near-UV exposure of human eyes after cataract surgery

Cannabinoid Receptor Type 1 Expression in the Developing Avian Retina: Morphological and Functional Correlation With the Dopaminergic System

Directory of Open Access Journals (Sweden)

Luzia da Silva Sampaio

2018-03-01

Full Text Available The avian retina has been used as a model to study signaling by different neuro- and gliotransmitters. It is unclear how dopaminergic and cannabinoid systems are related in the retina. Here we studied the expression of type 1 and 2 cannabinoid receptors (CB1 and CB2, as well as monoacylglycerol lipase (MAGL, the enzyme that degrades 2-arachidonoylglycerol (2-AG, during retina development. Our data show that CB1 receptor is highly expressed from embryonic day 5 (E5 until post hatched day 7 (PE7, decreasing its levels throughout development. CB1 is densely found in the ganglion cell layer (GCL and inner plexiform layer (IPL. CB2 receptor was also found from E5 until PE7 with a decrease in its contents from E9 afterwards. CB2 was mainly present in the lamination of the IPL at PE7. MAGL is expressed in all retinal layers, mainly in the IPL and OPL from E9 to PE7 retina. CB1 and CB2 were found both in neurons and glia cells, but MAGL was only expressed in Müller glia. Older retinas (PE7 show CB1 positive cells mainly in the INL and co-expression of CB1 and tyrosine hydroxylase (TH are shown in a few cells when both systems are mature. CB1 co-localized with TH and was heavily associated to D1 receptor labeling in primary cell cultures. Finally, cyclic AMP (cAMP was activated by the selective D1 agonist SKF38393, and inhibited when cultures were treated with WIN55, 212–2 (WIN in a CB1 dependent manner. The results suggest a correlation between the endocannabinoid and dopaminergic systems (DSs during the avian retina development. Activation of CB1 limits cAMP accumulation via D1 receptor activation and may influence embryological parameters during avian retina differentiation.

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.

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

Science.gov (United States)

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

2017-01-05

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

Action of UV-A and blue light on enzymes activity and accumulation of lipid peroxidation products in attached and detached frog retinas

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Lapina, Victoria A.; Doutsov, Alexander E.

1994-07-01

The effect of the UV-A and blue light on the accumulation of lipid peroxidation products and activities of succinate dehydrogenase and superoxide dismutase in the retina was examined in eye cup model of dark and light adapted frogs R. temporaria. Retinas were exposed to UV-A radiation (8 mW/cm2) and blue light (10 to 150 mW/cm2) for periods from 5 min to 1 hr. We have measured TBA-active products both in the retina homogenates and in the reaction media. Enzyme activities was measured in the retina homogenates only. The measurements revealed a significant increase in the endogenous and exogenous forms of lipid peroxidation products in the retina of dark adapted frog (1.6+/- 0.4; 1.4+/- 0.3 nmole TBA-active products per mg protein, respectively) compared to light adapted (0.85+/- 0.16; 0.32+/- 0.06 nmole TBA-active products per mg protein, respectively). In the same conditions succinate dehydrogenase activity was decline more than 50% but superoxide dismutase activity didn't decrease. Disorganized inner and outer segments were observed after 40 min exposures. No light microscopic changes were detected after 5 min exposures. Light damage was significantly higher in the retina of dark adapted frog. The results indicate that the retina from eye cup of dark adapted frog is more susceptible to UV-A and blue light damages.

Early changes in retinal structure and BMP2 expression in the retina and crystalline lens of streptozotocin-induced diabetic pigs.

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Jeong, Jae Seung; Lee, Woon-Kyu; Moon, Yeon Sung; Kim, Na Rae

2017-09-01

This study aims to evaluate early changes in retinal structure and BMP2 expression in the retina and crystalline lens by comparing streptozotocin-induced diabetic pigs and normal control group pigs. Five eye samples from five diabetic Micro-pigs (Medikinetics, Pyeongtaek, Korea) and five eye samples from five control pigs bred in a specific pathogen-free area were used. Diabetes was developed through intravenous injection of nicotinamide and streptozotocin, and the average fasting glucose level was maintained at 250 mg/dL or higher for 16 weeks. To evaluate BMP2 expression in the retina and crystalline lens, Western blotting was performed. In Hematoxylin and Eosin staining, most diabetic pigs showed structural abnormalities in the inner plexiform layer. The number of nuclei in the ganglion cell layer within the range of 10 4 µm 2 was 3.78±0.60 for diabetic pigs and 5.57±1.07 for control group pigs, showing a statistically significant difference. In immunohistochemical staining, diabetic retinas showed an overall increase in BMP2 expression. In Western blotting, the average BMP2/actin level of diabetic retinas was 1.19±0.05, showing a significant increase compared to the 1.06±0.03 of the control group retinas ( P =0.016). The BMP2/actin level of diabetic crystalline lenses was similar to the control group crystalline lenses ( P =0.730). Compared to control group pigs, the number of nuclei in the inner nuclear layer of retinas from streptozotocin-induced diabetic pigs decreased, while an increase in BMP2 expression was observed in the retina of diabetic pigs.

Design of a MEMS-based retina scanning system for biometric authentication

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Woittennek, Franziska; Knobbe, Jens; Pügner, Tino; Schelinski, Uwe; Grüger, Heinrich

2014-05-01

There is an increasing need for reliable authentication for a number of applications such as e commerce. Common authentication methods based on ownership (ID card) or knowledge factors (password, PIN) are often prone to manipulations and may therefore be not safe enough. Various inherence factor based methods like fingerprint, retinal pattern or voice identifications are considered more secure. Retina scanning in particular offers both low false rejection rate (FRR) and low false acceptance rate (FAR) with about one in a million. Images of the retina with its characteristic pattern of blood vessels can be made with either a fundus camera or laser scanning methods. The present work describes the optical design of a new compact retina laser scanner which is based on MEMS (Micro Electric Mechanical System) technology. The use of a dual axis micro scanning mirror for laser beam deflection enables a more compact and robust design compared to classical systems. The scanner exhibits a full field of view of 10° which corresponds to an area of 4 mm2 on the retinal surface surrounding the optical disc. The system works in the near infrared and is designed for use under ambient light conditions, which implies a pupil diameter of 1.5 mm. Furthermore it features a long eye relief of 30 mm so that it can be conveniently used by persons wearing glasses. The optical design requirements and the optical performance are discussed in terms of spot diagrams and ray fan plots.

Synaptic Remodeling Generates Synchronous Oscillations in the Degenerated Outer Mouse Retina

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Wadood eHaq

2014-09-01

Full Text Available During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs establish contacts with remnant cone photoreceptors (cones as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca2+ imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs, we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from HCs. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells.

Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig.

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Wei, Lihua; Ge, Li; Qin, Shucun; Shi, Yunzhi; Du, Changqing; Du, Hui; Liu, Liwei; Yu, Yang; Sun, Xuejun

2012-01-01

Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated the protective effects and mechanism of hydrogen-rich saline in a glutamate-induced retinal injury model. Retinal excitotoxicity was induced in healthy guinea pigs by injecting glutamate into the vitreous cavity. After 30 min, hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity or both. Seven days later, the retinal stress response was evaluated by examining the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose-regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the expression of the excitatory amino acid transporter 1(EAAT-1). The retinal histopathological changes were investigated, focusing on the thicknesses of the entire retina and its inner layer, the number of cells in the retinal ganglion cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich saline treatment reduced the loss of cells in the GCL and thinning of the retina and attenuated cellular morphological damage. These improvements were greatest in animals that received H(2) injections into both the vitreous and the peritoneal cavities. The hydrogen-rich saline also inhibited the expression of glial fibrillary acidic protein (GFAP) in Müller cells, CD11b in microglia, and iNOS and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery. This result likely occurs by inhibiting the activation of glial cells, decreasing the production of the iNOS and GRP78 and promoting glutamate clearance. Copyright © 2011 Elsevier Ltd. All rights reserved.

Uptake and release of [14C] GABA from rabbit retina synaptosomes

International Nuclear Information System (INIS)

Redburn, D.A.

1977-01-01

A partial separation of two synaptosomal fractions was achieved using modifications of conventional homogenization and centrifugation techniques. The two fractions contained morphologically distinct synaptosomal populations, receptor cell synaptosomes (large synaptosomes, P 1 ), and synaptosomes from the other cell types (smaller, conventional-sized synaptosomes, P 2 ). [ 14 C]GABA was bound and released from subcellular fractions from retina under conditions which support its role as a neurotransmitter in retina. On the other hand, [ 3 H]leucine, which is very likely a non-transmitter compound, was bound by retinal fractions but not released to the appropriate stimulation. [ 14 C]GABA binding and release sites were more prevalent in P 2 fractions. [ 14 C]GABA was bound by P 1 fractions containing photoreceptor synaptosomes; however, the K + stimulated release of [ 14 C]GABA appeared to be insensitive to external Ca 2+ . Possible mechanisms are discussed. (author)

Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R.

Science.gov (United States)

Cai, Siwei; Yang, Qianhui; Hou, Mengzhu; Han, Qian; Zhang, Hanyu; Wang, Jiantao; Qi, Chen; Bo, Qiyu; Ru, Yusha; Yang, Wei; Gu, Zhongxiu; Wei, Ruihua; Cao, Yunshan; Li, Xiaorong; Zhang, Yan

2018-01-01

Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH's anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH's protection. Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested

The utilization of glutamine by the retina: an autoradiographic and metabolic study

International Nuclear Information System (INIS)

Voaden, M.J.; Lake, N.; Marshall, J.; Morjaria, B.

1978-01-01

The cells able to accumulate exogenously applied [ 3 H] glutamine in rat, cat, frog, pigeon and guinea pig retinas have been located by autoradiography, and the fate of the labelled glutamine, as regards its incorporation into aspartic, glutamic and γ-amino-butyric acids, followed for 60 min. The results support the notion of glutamine as a precursor of transmitter amino acids in some neurones. In particular, it would appear to be a source of a relatively stable pool of GABA which may be located, with species variation, in amacrine or ganglion cells. In the pigeon retina glutamate pool incorporates and retains a major percentage of the label, and perikarya in the middle of the inner nuclear layer of the tissue are predominantly labelled. (author)

Localization of glycine-containing neurons in the Macaca monkey retina

International Nuclear Information System (INIS)

Hendrickson, A.E.; Koontz, M.A.; Pourcho, R.G.; Sarthy, P.V.; Goebel, D.J.

1988-01-01

Autoradiography following 3H-glycine (Gly) uptake and immunocytochemistry with a Gly-specific antiserum were used to identify neurons in Macaca monkey retina that contain a high level of this neurotransmitter. High-affinity uptake of Gly was shown to be sodium dependent whereas release of both endogenous and accumulated Gly was calcium dependent. Neurons labeling for Gly included 40-46% of the amacrine cells and nearly 40% of the bipolars. Synaptic labeling was seen throughout the inner plexiform layer (IPL) but with a preferential distribution in the inner half. Bands of labeled puncta occurred in S2, S4, and S5. Both light and postembedding electron microscopic (EM) immunocytochemistry identified different types of amacrine and bipolar cell bodies and their synaptic terminals. The most heavily labeled Gly+ cell bodies typically were amacrine cells having a single, thick, basal dendrite extending deep into the IPL and, at the EM level, electron-dense cytoplasm and prominent nuclear infoldings. This cell type may be homologous with the Gly2 cell in human retina and the AII/Gly2 of cat retina. Gly+ amacrines synapse most frequently onto Gly- amacrines and both Gly- and Gly+ bipolars. Gly+ bipolar cells appeared to be cone bipolars because their labeled dendrites could be traced only to cone pedicles. The pattern of these labeled dendritic trees indicated that both diffuse and midget types of biopolars were Gly+. The EM distribution of labeled synapses showed Gly+ amacrine synapses throughout the IPL, but these composed only 11-23% of the amacrine population. Most of the Gly+ bipolar terminals were in the inner IPL, where 70% of all bipolar terminals were labeled

Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometry.

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Zemski Berry, Karin A; Gordon, William C; Murphy, Robert C; Bazan, Nicolas G

2014-03-01

MALDI imaging mass spectrometry (IMS) was used to characterize lipid species within sections of human eyes. Common phospholipids that are abundant in most tissues were not highly localized and observed throughout the accessory tissue, optic nerve, and retina. Triacylglycerols were highly localized in accessory tissue, whereas sulfatide and plasmalogen glycerophosphoethanolamine (PE) lipids with a monounsaturated fatty acid were found enriched in the optic nerve. Additionally, several lipids were associated solely with the inner retina, photoreceptors, or retinal pigment epithelium (RPE); a plasmalogen PE lipid containing DHA (22:6), PE(P-18:0/22:6), was present exclusively in the inner retina, and DHA-containing glycerophosphatidylcholine (PC) and PE lipids were found solely in photoreceptors. PC lipids containing very long chain (VLC)-PUFAs were detected in photoreceptors despite their low abundance in the retina. Ceramide lipids and the bis-retinoid, N-retinylidene-N-retinylethanolamine, was tentatively identified and found only in the RPE. This MALDI IMS study readily revealed the location of many lipids that have been associated with degenerative retinal diseases. Complex lipid localization within retinal tissue provides a global view of lipid organization and initial evidence for specific functions in localized regions, offering opportunities to assess their significance in retinal diseases, such as macular degeneration, where lipids have been implicated in the disease process.

Abnormal levels of histone methylation in the retinas of diabetic rats are reversed by minocycline treatment

DEFF Research Database (Denmark)

Wang, Wenjun; Sidoli, Simone; Zhang, Wenquan

2017-01-01

67% of these marks had their relative abundance restored to non-diabetic levels after minocycline treatment. Mono-and di-methylation states of histone H4 lysine 20 (H4K20me1/me2), markers related to DNA damage response, were found to be up-regulated in the retinas of diabetic rats and restored......In this study we quantified the alterations of retinal histone post-translational modifications (PTMs) in diabetic rats using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach. Some diabetic rats were subsequently treated with minocycline, a tetracycline antibiotic, which has...... been shown to inhibit the diabetes-induced chronic inflammation in the retinas of rodents. We quantified 266 differentially modified histone peptides, including 48 out of 83 methylation marks with significantly different abundancein retinas of diabetic rats as compared to non-diabetic controls. About...

Cytogenesis in the monkey retina

International Nuclear Information System (INIS)

La Vail, M.M.; Rapaport, D.H.; Rakic, P.

1991-01-01

Time of cell origin in the retina of the rhesus monkey (Macaca mulatta) was studied by plotting the number of heavily radiolabeled nuclei in autoradiograms prepared from 2- to 6-month-old animals, each of which was exposed to a pulse of 3H-thymidine (3H-TdR) on a single embryonic (E) or postnatal (P) day. Cell birth in the monkey retina begins just after E27, and approximately 96% of cells are generated by E120. The remaining cells are produced during the last (approximately 45) prenatal days and into the first several weeks after birth. Cell genesis begins near the fovea, and proceeds towards the periphery. Cell division largely ceases in the foveal and perifoveal regions by E56. Despite extensive overlap, a class-specific sequence of cell birth was observed. Ganglion and horizontal cells, which are born first, have largely congruent periods of cell genesis with the peak between E38 and E43, and termination around E70. The first labeled cones were apparent by E33, and their highest density was achieved between E43 and E56, tapering to low values at E70, although some cones are generated in the far periphery as late as E110. Amacrine cells are next in the cell birth sequence and begin genesis at E43, reach a peak production between E56 and E85, and cease by E110. Bipolar cell birth begins at the same time as amacrines, but appears to be separate from them temporally since their production reaches a peak between E56 and E102, and persists beyond the day of birth. Mueller cells and rod photoreceptors, which begin to be generated at E45, achieve a peak, and decrease in density at the same time as bipolar cells, but continue genesis at low density on the day of birth. Thus, bipolar, Mueller, and rod cells have a similar time of origin

MEMS scanner mirror based system for retina scanning and in eye projection

Science.gov (United States)

Woittennek, Franziska; Knobbe, Jens; Pügner, Tino; Dallmann, Hans-Georg; Schelinski, Uwe; Grüger, Heinrich

2015-02-01

Many applications could benefit from miniaturized systems to scan blood vessels behind the retina in the human eye, so called "retina scanning". This reaches from access control to sophisticated security applications and medical devices. High volume systems for consumer applications require low cost and a user friendly operation. For example this includes no need for removal of glasses and self-adjustment, in turn guidance of focus and point of attraction by simultaneous projection for the user. A new system has been designed based on the well-known resonantly driven 2-d scanner mirror of Fraunhofer IPMS. A combined NIR and VIS laser system illuminates the eye through an eye piece designed for an operating distance allowing the use of glasses and granting sufficient field of view. This usability feature was considered to be more important than highest miniaturization. The modulated VIS laser facilitates the projection of an image directly onto the retina. The backscattered light from the continuous NIR laser contains the information of the blood vessels and is detected by a highly sensitive photo diode. A demonstrational setup has been realized including readout and driving electronics. The laser power was adjusted to an eye-secure level. Additional security features were integrated. Test measurements revealed promising results. In a first demonstration application the detection of biometric pattern of the blood vessels was evaluated for issues authentication in.

Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-4.

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Bikbova, Guzel; Oshitari, Toshiyuki; Yamamoto, Shuichi

2013-10-09

The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free control culture media, (2) glucose-advanced glycation end-products-bovine serum albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media, (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in

Modeling of corneal and retinal pharmacokinetics after periocular drug administration.

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Amrite, Aniruddha C; Edelhauser, Henry F; Kompella, Uday B

2008-01-01

To develop pharmacokinetics models to describe the disposition of small lipophilic molecules in the cornea and retina after periocular (subconjunctival or posterior subconjunctival) administration. Compartmental pharmacokinetics analysis was performed on the corneal and retinal data obtained after periocular administration of 3 mg of celecoxib (a selective COX-2 inhibitor) to Brown Norway (BN) rats. Berkeley Madonna, a differential and difference equation-based modeling software, was used for the pharmacokinetics modeling. The data were fit to different compartment models with first-order input and disposition, and the best fit was selected on the basis of coefficient of regression and Akaike information criteria (AIC). The models were validated by using the celecoxib data from a prior study in Sprague-Dawley (SD) rats. The corneal model was also fit to the corneal data for prednisolone at a dose of 2.61 mg in albino rabbits, and the model was validated at two other doses of prednisolone (0.261 and 26.1 mg) in these rabbits. Model simulations were performed with the finalized model to understand the effect of formulation on corneal and retinal pharmacokinetics after periocular administration. Celecoxib kinetics in the BN rat cornea can be described by a two-compartment (periocular space and cornea, with a dissolution step for periocular formulation) model, with parallel elimination from the cornea and the periocular space. The inclusion of a distribution compartment or a dissolution step for celecoxib suspension did not lead to an overall improvement in the corneal data fit compared with the two-compartment model. The more important parameter for enhanced fit and explaining the apparent lack of an increase phase in the corneal levels is the inclusion of the initial leak-back of the dose from the periocular space into the precorneal area. The predicted celecoxib concentrations from this model also showed very good correlation (r = 0.99) with the observed values in

Heat shock protein 70 and heat shock protein 90 expression in light- and dark-adapted adult octopus retinas.

Science.gov (United States)

Ochoa, Gina H; Clark, Ying Mei; Matsumoto, Brian; Torres-Ruiz, Jose A; Robles, Laura J

2002-02-01

Light- and dark-adaptation leads to changes in rhabdom morphology and photopigment distribution in the octopus retina. Molecular chaperones, including heat shock proteins (Hsps), may be involved in specific signaling pathways that cause changes in photoreceptor actin- and tubulin-based cytoskeletons and movement of the photopigments, rhodopsin and retinochrome. In this study, we used immunoblotting, in situ RT-PCR, immunofluorescence and confocal microscopy to localize the inducible form of Hsp70 and the larger Hsp90 in light- and dark-adapted and dorsal and ventral halves of adult octopus retinas. The Hsps showed differences in distribution between the light and dark and in dorsal vs. ventral position in the retina. Double labeling confocal microscopy co-localized Hsp70 with actin and tubulin, and Hsp90 with the photopigment, retinochrome. Our results demonstrate the presence of Hsp70 and Hsp90 in otherwise non-stressed light- and dark-adapted octopus retinas. These Hsps may help stabilize the cytoskeleton, important for rhabdom structure, and are perhaps involved in the redistribution of retinochrome in conditions of light and dark.

Distribution of light in the human retina under natural viewing conditions

Science.gov (United States)

Gibert, Jorge C.

Age-related macular degeneration (AMD) is the leading cause of blindness inAmerica. The fact that AMD wreaks most of the damage in the center of the retina raises the question of whether light, integrated over long periods, is more concentrated in the macula. A method, based on eye-tracking, was developed to measure the distribution of light in the retina under natural viewing conditions. The hypothesis was that integrated over time, retinal illumination peaked in the macula. Additionally a possible relationship between age and retinal illumination was investigated. The eye tracker superimposed the subject's gaze position on a video recorded by a scene camera. Five informed subjects were employed in feasibility tests, and 58 naive subjects participated in 5 phases. In phase 1 the subjects viewed a gray-scale image. In phase 2, they observed a sequence of photographic images. In phase 3 they viewed a video. In phase 4, they worked on a computer; in phase 5, the subjects walked around freely. The informed subjects were instructed to gaze at bright objects in the field of view and then at dark objects. Naive subjects were allowed to gaze freely for all phases. Using the subject's gaze coordinates, and the video provided by the scene camera, the cumulative light distribution on the retina was calculated for ˜15° around the fovea. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark objects respectively. The light distribution maps obtained from the naive subjects presented a tendency to peak in the macula for phases 1, 2, and 3, a consistent tendency in phase 4 and a variable tendency in phase 5. The feasibility of using an eye-tracker system to measure the distribution of light in the retina was demonstrated, thus helping to understand the role played by light exposure in the etiology of AMD. Results showed that a tendency for light to peak in the macula is a characteristic of some

Finestructure of the retina in Garra rufa (cypriniae, Teleostei)

International Nuclear Information System (INIS)

Al-Adhami, A. M.; Mir, S.

1999-01-01

The light - and dark-adapted retina of the freshwater, bottom-dweller tele ost, Ga rra rufa (Heck el, 1843) was studied under light and electron microscopes. The fish is a fist record in having both falcifrom process and vit real blood circulation and the hyaloid artery from which it developers. A number of acute vision areas represented by increased density of ganglion cell soma ta are evident. The dark-adapted retina is characterized by notably large photoreceptor terminals (rod spherules and cone placidas). A rod spherules has single synaptic ribbon, whereas a cone pedicle has three to four. The inner nuclear layer is composed of the so meta of horizontal, bipolar and amsacrine cells in addition to nuclei of Muller cells. The outer nuclear layer, on the other hand, is composed of two-three rows of rod nuclei and one row of cone nuclei. The photoreceptor cells include rods and single and double cones. The rod outer segments have deep and/or shallow incisor. Cone ellipsoid may have ellipsosomes. These are shown to develop from one of the apical mitochondria of the ellipsoid- Retinomotor movement involves both the photoreceptor cells and the pigment epithelium. (authors). 11 refs., 14 figs

Msx1 is expressed in retina endothelial cells at artery branching sites

Directory of Open Access Journals (Sweden)

Miguel Lopes

2012-02-01

Msx1 and Msx2 encode homeodomain transcription factors that play a role in several embryonic developmental processes. Previously, we have shown that in the adult mouse, Msx1lacZ is expressed in vascular smooth muscle cells (VSMCs and pericytes, and that Msx2lacZ is also expressed in VSMCs as well as in a few endothelial cells (ECs. The mouse retina and choroid are two highly vascularized tissues. Vessel alterations in the retina are associated with several human diseases and the retina has been intensely used for angiogenesis studies, whereas the choroid has been much less investigated. Using the Msx1lacZ and Msx2lacZ reporter alleles, we observed that Msx2 is not expressed in the eye vascular tree in contrast to Msx1, for which we establish the spatial and temporal expression pattern in these tissues. In the retina, expression of Msx1 takes place from P3, and by P10, it becomes confined to a subpopulation of ECs at branching points of superficial arterioles. These branching sites are characterized by a subpopulation of mural cells that also show specific expression programs. Specific Msx gene inactivation in the endothelium, using Msx1 and Msx2 conditional mutant alleles together with a Tie2-Cre transgene, did not lead to conspicuous structural defects in the retinal vascular network. Expression of Msx1 at branching sites might therefore be linked to vessel physiology. The retinal blood flow is autonomously regulated and perfusion of capillaries has been proposed to depend on arteriolar precapillary structures that might be the sites for Msx1 expression. On the other hand, branching sites are subject to shear stress that might induce Msx1 expression. In the choroid vascular layer Msx1lacZ is expressed more broadly and dynamically. At birth Msx1lacZ expression takes place in the endothelium but at P21 its expression has shifted towards the mural layer. We discuss the possible functions of Msx1 in the eye vasculature.

Msx1 is expressed in retina endothelial cells at artery branching sites.

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Lopes, Miguel; Goupille, Olivier; Saint Cloment, Cécile; Robert, Benoît

2012-04-15

Msx1 and Msx2 encode homeodomain transcription factors that play a role in several embryonic developmental processes. Previously, we have shown that in the adult mouse, Msx1(lacZ) is expressed in vascular smooth muscle cells (VSMCs) and pericytes, and that Msx2(lacZ) is also expressed in VSMCs as well as in a few endothelial cells (ECs). The mouse retina and choroid are two highly vascularized tissues. Vessel alterations in the retina are associated with several human diseases and the retina has been intensely used for angiogenesis studies, whereas the choroid has been much less investigated. Using the Msx1(lacZ) and Msx2(lacZ) reporter alleles, we observed that Msx2 is not expressed in the eye vascular tree in contrast to Msx1, for which we establish the spatial and temporal expression pattern in these tissues. In the retina, expression of Msx1 takes place from P3, and by P10, it becomes confined to a subpopulation of ECs at branching points of superficial arterioles. These branching sites are characterized by a subpopulation of mural cells that also show specific expression programs. Specific Msx gene inactivation in the endothelium, using Msx1 and Msx2 conditional mutant alleles together with a Tie2-Cre transgene, did not lead to conspicuous structural defects in the retinal vascular network. Expression of Msx1 at branching sites might therefore be linked to vessel physiology. The retinal blood flow is autonomously regulated and perfusion of capillaries has been proposed to depend on arteriolar precapillary structures that might be the sites for Msx1 expression. On the other hand, branching sites are subject to shear stress that might induce Msx1 expression. In the choroid vascular layer Msx1(lacZ) is expressed more broadly and dynamically. At birth Msx1(lacZ) expression takes place in the endothelium but at P21 its expression has shifted towards the mural layer. We discuss the possible functions of Msx1 in the eye vasculature.

Microscopic hyperspectral imaging studies of normal and diabetic retina of rats

Institute of Scientific and Technical Information of China (English)

2008-01-01

A microscopic hyperspectral imager was developed based on the microscopic technology and the spectral imaging technology. Some microscopic hyperspectral images of retina sections of the normal, the diabetic, and the treated rats were collected by the new imager. Single-band images and pseudo-color images of each group were obtained and the typical transmittance spectrums were ex-tracted. The results showed that the transmittance of outer nuclear layer cells of the diabetic group was generally higher than that of the normal. A small absorption peak appeared near the 180th band in the spectrum of the diabetic group and this peak weakened or disappeared in the spectrum of the treated group. Our findings indicate that the microscopic hyperspectral images include wealthy information of retina sections which is helpful for the ophthalmologist to reveal the pathogenesis of diabetic reti-nopathy and explore the therapeutic effect of drugs.

[Expression of vimentin and GFAP and development of the retina in the trout].

Science.gov (United States)

De Guevara, R; Pairault, C; Pinganaud, G

1994-08-01

The glial cell development was studied during the edification of the retina and the optic tract, in a teleost, the rainbow trout. The intermediate filament proteins, vimentin and glial fibrillary acidic protein (GFAP) were visualized by an indirect immunohistochemical method. Results show that both vimentin and GFAP are early expressed in the developing retina and, particularly in the Müller cells, a coexpression of vimentin and GFAP is observed from embryonic to adult stages. The ganglion cell layer and the optic fiber layer both exhibit GFAP-positive structures. The deep staining for GFAP is also seen in the optic nerve and induces us to credit astrocyte-like cells with a leading role in the pattern formation of this tract.

Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

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Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.

2012-01-01

It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water

Radicals excess in the retina: A model for light flashes in space

International Nuclear Information System (INIS)

Narici, L.; De Martino, A.; Brunetti, V.; Rinaldi, A.; Sannita, W.G.; Paci, M.

2009-01-01

The risk due to cosmic radiation is a major issue in planning future missions to the Moon or Mars and would be critical if inadequately addressed. Functional risks must also be considered. The perception of light flashes reported by astronauts in space, and ascribed mostly to the action of ionizing radiation in the eye (retina), is an evidence for radiation functional interaction. No detailed model of the ion/retina interaction is yet available. Here we present the first model for a generation mechanism compatible with light flashes in space, and the results of in vitro tests supporting it. The model can be a common end point for the interactions between ionizing radiation and visual system in space. It would also support the assessment of functional radiation risks in space.

Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat

DEFF Research Database (Denmark)

Rath, Martin F; Morin, Fabrice; Shi, Qiong

2007-01-01

. This confirmed the presence of Otx2 mRNA in both the embryonic retinal pigment epithelium and the developing neural retina. During development, the expression of Otx2 persists in the pigment epithelium, whereas Otx2 expression of the neural retina becomes progressively restricted to the outer nuclear layer......Otx2 and Crx are vertebrate orthologs of the orthodenticle family of homeobox genes, which are involved in retinal development. In this study, the temporal expression patterns of Otx2 and Crx in the rat retina during embryonic and postnatal stages of development were analyzed in detail...... and the outer part of the inner nuclear layer. Immunohistochemistry revealed that Otx2 protein is also present in cell bodies of the ganglion cell layer, which does not contain the Otx2 transcript, suggesting that Otx2 protein is synthesized in cell bodies of the bipolar neurons and then transported...

The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications

Directory of Open Access Journals (Sweden)

Thomas Schwitzer

2016-01-01

Full Text Available Cannabis is one of the most prevalent drugs used in industrialized countries. The main effects of Cannabis are mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.

Dialogue and Exchange of Information about Grade Inflation Can Counteract Its Effects

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Barriga, Alvaro Q.; Cooper, Eric K.; Gawelek, Mary Ann; Butela, Kristin; Johnson, Elizabeth

2008-01-01

This investigation documents an intervention that successfully counteracted a grade inflation trend at a small, Catholic, liberal arts university in the eastern United States. The intervention produced a significant drop in grades awarded by full-time faculty, but not by adjunct faculty who were not yet included in the intervention. Institutional…

Possible influences of lutein and zeaxanthin on the developing retina.

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Zimmer, J Paul; Hammond, Billy R

2007-03-01

The carotenoids lutein and zeaxanthin (LZ) are found throughout the central nervous system but reach their highest concentration within the macular region of the primate retina where they are commonly referred to as the macular pigments. Although LZ are a major integral feature of the central fovea, no information currently exists regarding the effects of variability in the concentration of these pigments on the developing retina. In particular, the long-term effects of very low levels of macular pigment are not known and potentially meaningful. Macular pigment levels depend upon dietary intake since LZ cannot be synthesized de novo. Infants with low intake of LZ (eg, infants receiving unfortified infant formula or breast milk from mothers with low carotenoid diets) would be expected to have considerably lower macular pigment compared with infants with high LZ intake (eg, breast-fed infants with mothers on carotenoid-rich diets). In this paper we discuss possible implications of this difference and the available evidence suggesting that LZ could influence the developing visual system.

Changes in acetylcholine release from the chick retina are not associated with myopia development

International Nuclear Information System (INIS)

Vessey, K.A.; Cotriall, C.L.; McBrien, N.A.

2002-01-01

Full text: The effectiveness of muscarinic receptor antagonists in inhibiting myopia progression in animal models and humans implicates cholinergic signalling in ocular growth regulation. Therefore to determine if changes in the release of acetylcholine from the retina are involved in myopia development, the efflux of acetylcholine from the in vitro retina of normal and myopic chick eyes was investigated. Chicks were monocularly deprived (MD) of pattern vision with translucent occluders for 2 or 7 days and refractive error of MD groups and age matched normals was monitored using retinoscopy (n=6 each group). 3 H-choline-Cl (1 Ci in 7μL) was injected into the vitreous of each eye under 2.5% halothane anaesthesia. After 1hr, the eyes were enucleated, under terminal anaesthesia (sodium pentobarbital, 120 mg/kg, im). Retinas were flat-mounted on acetate filter discs and superfused with oxygenated physiological saline solution (PSS) for 30min at 0.4mL/min. Five baseline fractions were collected (B1-B5), then three stimulated fractions were collected in the presence of PSS containing 50mM KCl (K1-K3) at 2min intervals. 3 H-acetylcholine ( 3 H-ACh) in each fraction was quantified by liquid scintillation counting. Significant amounts of myopia were induced in MD eyes after 2 (-5.1±0.8D) and 7 days (-18.8±2.4D) relative to control eyes (paired t-test p 3 H-ACh release was 146±15% above basal levels (K2/B1%) from retinas of normal animals. After 2 days MD, there was no significant difference between KCl-evoked release of 3 H-ACh from deprived eyes (147 39%) compared to control eyes (198±61%, paired t-test, p=0.27) or the eyes of normal animals (ANOVA, p>0.5). Similar results were obtained following 7 days MD. The results demonstrate that evoked acetylcholine release from the chick retina of myopic eyes is unaltered relative to control or normal eyes using an in vitro approach. Copyright (2002) Australian Neuroscience Society

Pivotal roles of Fezf2 in differentiation of cone OFF bipolar cells and functional maturation of cone ON bipolar cells in retina.

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Suzuki-Kerr, Haruna; Iwagawa, Toshiro; Sagara, Hiroshi; Mizota, Atsushi; Suzuki, Yutaka; Watanabe, Sumiko

2018-06-01

During development of the retina, common retinal progenitor cells give rise to six classes of neurons that subsequently further diversify into more than 55 subtypes of neuronal subtypes. Here, we have investigated the expression and function of Fezf2, Fez zinc finger family of protein, in the developing mouse retina. Expression of Fezf2 transcripts was strongly observed in the embryonic retinal progenitors at E14.5 and declined quickly in subsequent development of retina. Then, in postnatal stage at around day 8, Fezf2 was transiently expressed then declined again. Loss-of-function analysis using retinas from mice in which Fezf2 coding region was substituted with β-galactosidase showed that Fezf2 is expressed in a subset of cone OFF bipolar cells and required for their differentiation. Using electroretinogram, we found that Fezf2 knockout retina exhibited significantly reduced photopic b-wave, suggesting functional abnormality of cone ON bipolar cells. Furthermore, reduced expression of synaptic protein Trpm1 and structural alteration of ON bipolar cell invagination, both of which affected cone photoreceptor terminal synaptic activity, was identified by transmission electron microscopy and immunohistochemistry, respectively. Taken together, our results show that Fezf2 is indispensable in differentiation of bipolar precursors into cone OFF bipolar cells and in functional maturation of cone ON bipolar cells during development of mouse retina. These results contribute to our understanding of how diversity of neuronal subtypes and hence specificity of neuronal connections are established in the retina by intrinsic cues. Copyright © 2018 Elsevier Ltd. All rights reserved.

Some Problems of the Implementation of Administrative Responsibility for Violations of the Legislation on Contract System in the Procurement Sphere

OpenAIRE

Andrei E. Yuritsin; Yurii B. Lavrov

2017-01-01

The article considers the issues of application of Article 6.9 of the Code of Administrative Offences of the Russian Federation and the significance of the practice of implementation of this legal norm to counteraction to illegal drug use. The author estimates the possibility of dealing all cases of illegal use of narcotic drugs and psychotropic substances and their analogues by law enforcement practice as well as the sufficiency of administrative penalties provided for by the Article. Critic...

Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

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Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

2016-12-01

Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

Adaptive optics imaging of the retina

Directory of Open Access Journals (Sweden)

Rajani Battu

2014-01-01

Full Text Available Adaptive optics is a relatively new tool that is available to ophthalmologists for study of cellular level details. In addition to the axial resolution provided by the spectral-domain optical coherence tomography, adaptive optics provides an excellent lateral resolution, enabling visualization of the photoreceptors, blood vessels and details of the optic nerve head. We attempt a mini review of the current role of adaptive optics in retinal imaging. PubMed search was performed with key words Adaptive optics OR Retina OR Retinal imaging. Conference abstracts were searched from the Association for Research in Vision and Ophthalmology (ARVO and American Academy of Ophthalmology (AAO meetings. In total, 261 relevant publications and 389 conference abstracts were identified.

Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina.

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Namihira, M; Honma, S; Abe, H; Tanahashi, Y; Ikeda, M; Honma, K

1999-08-13

Circadian expression and light-responsiveness of the mammalian clock genes, Clock and BMAL1, in the rat retina were examined by in situ hydbribization under constant darkness. A small but significant daily variation was detected in the Clock transcript level, but not in BMAL1. Light increased the Clock and BMAL1 expressions significantly when examined 60 min after exposure. The light-induced gene expression was phase-dependent for Clock and peaked at ZT2, while rather constant throughout the day for BMAL1. These findings suggest that Clock and BMAL1 play different roles in the generation of circadian rhytm in the retina from those in the suprachiasmatic nucleus. Different roles are also suggested between the two genes in the photic signal transduction in the retina.

Webinar Presentation: Vitamins, Minerals and Metals: Do Healthy Diets Counteract Health Effects of Toxicants?

Science.gov (United States)

This presentation, Vitamins, Minerals and Metals: Do Healthy Diets Counteract Health Effects of Toxicants?, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Food and Children's Health held on Dec. 9, 2015.

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

International Nuclear Information System (INIS)

Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

1988-01-01

We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

X-ray microprobe analysis of the retina and RPE in sheep with ovine ceroid-lipofuscinosis

International Nuclear Information System (INIS)

Samuelson, D.A.; Armstrong, D.; Jolly, R.

1990-01-01

Ovine ceroid-lipofuscinosis (OCL) is one animal model for the human condition, and because autofluorescent lipopigments are prominent in the brain and eye, it may also prove useful as a model for aging. For example, a progressive decline in electrical recording from brain and retina are observed in both aging and OCL. Samples of retinal and retinal pigment epithelial (RPE) tissues were obtained from a young control. 2 animals with OCL and a normal aged sheep. Specimens were cryo-fractured and examined by scanning electron microscopy/x-ray microanalysis. Measurements made of 6 individual cells in the ganglion layer of OCL specimens, the remainder of the retina, and RPE showed age-related changes in zinc, iron, and copper which were associated with lipopigment accumulation in the RPE. There was marked decrease in phosphate, sulfur, and manganese levels, as photoreceptor cells and their outer segments are lost in the disease process. This is the first report of metal analysis in the retina and RPE in a disease entity, and as a function of normal aging

Electroretinography: A biopotential to assess the function/dysfunction of the retina

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Quintana, Quinteros; Benedetto, M. L.; Maldonado, M. M.; de Payer E., A. C. Vera; Contin, M. A.

2016-04-01

The Electroretinography (ERG) is a noninvasive technique that allows the assessment of functional integrity of the retina. The ERG recordings are biopotencials acquired in the corneal surface as a response of retinal tissue against controlled light stimuli. In clinical ophthalmology ERG is not commonly used but nowadays, because of the high incidence of degenerative diseases of the retina (RD), its use should be increased. Like other biopotentials as electrocardiography (ECG), electroencephalogram (EEG) and electromyography (EMG), ERG is a low amplitude signal, in this case a few hundred of microvolts (µV), which must be fitted and processed. The ERG signals are affected in morphology in the presence of pathologies that affects the integrity of the different retinal cell groups, for example due to some RD. In advanced cases of RD recordings can be abolished in the time domain; and yet in them it is believed that there is relevant clinical information making the ERG a great potential diagnostic tool.

Lactate Transport and Receptor Actions in Retina

DEFF Research Database (Denmark)

Kolko, Miriam; Vosborg, Fia; Henriksen, Jens Ulrik Lütken

2016-01-01

known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions......In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also...

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.

Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

Science.gov (United States)

Sarker, Protim; Ahmed, Sultan; Tiash, Snigdha; Rekha, Rokeya Sultana; Stromberg, Roger; Andersson, Jan; Bergman, Peter; Gudmundsson, Gudmundur H; Agerberth, Birgitta; Raqib, Rubhana

2011-01-01

Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs) that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB) reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB), a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR) and release of the CAP-18 peptide/protein in stool (Western blot). Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from secondary respiratory infections that frequently are the lethal causes in

A Retina-Like Dual Band Organic Photosensor Array for Filter-Free Near-Infrared-to-Memory Operations.

Science.gov (United States)

Wang, Hanlin; Liu, Hongtao; Zhao, Qiang; Ni, Zhenjie; Zou, Ye; Yang, Jie; Wang, Lifeng; Sun, Yanqiu; Guo, Yunlong; Hu, Wenping; Liu, Yunqi

2017-08-01

Human eyes use retina photoreceptor cells to absorb and distinguish photons from different wavelengths to construct an image. Mimicry of such a process and extension of its spectral response into the near-infrared (NIR) is indispensable for night surveillance, retinal prosthetics, and medical imaging applications. Currently, NIR organic photosensors demand optical filters to reduce visible interference, thus making filter-free and anti-visible NIR imaging a challenging task. To solve this limitation, a filter-free and conformal, retina-inspired NIR organic photosensor is presented. Featuring an integration of photosensing and floating-gate memory modules, the device possesses an acute color distinguishing capability. In general, the retina-like photosensor transduces NIR (850 nm) into nonvolatile memory and acts as a dynamic photoswitch under green light (550 nm). In doing this, a filter-free but color-distinguishing photosensor is demonstrated that selectively converts NIR optical signals into nonvolatile memory. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Common Variants in the COL4A4 Gene Confer Susceptibility to Lattice Degeneration of the Retina

OpenAIRE

Meguro, Akira; Ideta, Hidenao; Ota, Masao; Ito, Norihiko; Ideta, Ryuichi; Yonemoto, Junichi; Takeuchi, Masaki; Uemoto, Riyo; Nishide, Tadayuki; Iijima, Yasuhito; Kawagoe, Tatsukata; Okada, Eiichi; Shiota, Tomoko; Hagihara, Yuta; Oka, Akira

2012-01-01

Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite...

Immunohistochemical Localization of an Isoform of TRK-Fused Gene-Like Protein in the Rat Retina

International Nuclear Information System (INIS)

Masuda, Chiaki; Takeuchi, Shigeko; Bisem, Naomi J.; Vincent, Steven R.; Tooyama, Ikuo

2014-01-01

The TRK-fused gene (TFG) was originally identified in chromosome translocation events, creating a pair of oncogenes in some cancers, and was recently demonstrated as the causal gene of hereditary motor and sensory neuropathy with proximal dominant involvement. Recently, we cloned an alternative splicing variant of Tfg from a cDNA library of the rat retina, tentatively naming it retinal Tfg (rTfg). Although the common form of Tfg is ubiquitously expressed in most rat tissues, rTfg expression is localized to the central nervous system. In this study, we produced an antibody against an rTFG-specific amino acid sequence and used it to examine the localization of rTFG-like protein in the rat retina by immunohistochemistry and Western blots. Western blot analysis showed that the antibody detected a single band of 24 kDa in the rat retina. When we examined rTFG recombinant protein, the antibody detected two bands of about 42 kDa and 24 kDa. The results suggest that the 24 kDa rTFG-like protein is a fragment of rTFG. In our immunohistochemical studies of the rat retina, rTFG-like immunoreactivity was observed in all calbindin D-28K-positive horizontal cells and in some syntaxin 1-positive amacrine cells (ACs). In addition, the rTFG-like immunopositive ACs were actually glycine transporter 1-positive glycinergic or glutamate decarboxylase-positive GABAergic ACs. Our findings indicate that this novel 24 kDa rTFG-like protein may play a specific role in retinal inhibitory interneurons

Pushing the limits of photoreception in twilight conditions: The rod-like cone retina of the deep-sea pearlsides

KAUST Repository

Busserolles, Fanny de

2017-11-09

Most vertebrates have a duplex retina comprising two photoreceptor types, rods for dim-light (scotopic) vision and cones for bright-light (photopic) and color vision. However, deep-sea fishes are only active in dim-light conditions; hence, most species have lost their cones in favor of a simplex retina composed exclusively of rods. Although the pearlsides, Maurolicus spp., have such a pure rod retina, their behavior is at odds with this simplex visual system. Contrary to other deep-sea fishes, pearlsides are mostly active during dusk and dawn close to the surface, where light levels are intermediate (twilight or mesopic) and require the use of both rod and cone photoreceptors. This study elucidates this paradox by demonstrating that the pearlside retina does not have rod photoreceptors only; instead, it is composed almost exclusively of transmuted cone photoreceptors. These transmuted cells combine the morphological characteristics of a rod photoreceptor with a cone opsin and a cone phototransduction cascade to form a unique photoreceptor type, a rod-like cone, specifically tuned to the light conditions of the pearlsides\\' habitat (blue-shifted light at mesopic intensities). Combining properties of both rods and cones into a single cell type, instead of using two photoreceptor types that do not function at their full potential under mesopic conditions, is likely to be the most efficient and economical solution to optimize visual performance. These results challenge the standing paradigm of the function and evolution of the vertebrate duplex retina and emphasize the need for a more comprehensive evaluation of visual systems in general.

Simultaneous in vivo imaging of melanin and lipofuscin in the retina with multimodal photoacoustic ophthalmoscopy

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Zhang, Xiangyang; Zhang, Hao F.; Zhou, Lixiang; Jiao, Shuliang

2012-02-01

We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective vs. exacerbate) in the RPE in the aging process. We successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

Three dimensional reconstruction of tomographic images of the retina

International Nuclear Information System (INIS)

Glittenberg, C.; Zeiler, F.; Falkner, C.; Binder, S.; Povazay, B.; Hermann, B.; Drexler, W.

2007-01-01

The development of a new display system for the three-dimensional visualization of tomographic images in ophthalmology. Specifically, a system that can use stacks of B-mode scans from an ultrahigh resolution optical tomography examination to vividly display retinal specimens as three-dimensional objects. Several subroutines were programmed in the rendering and raytracing program Cinema 4D XL 9.102 Studio Bundle (Maxon Computer Inc., Friedrichsburg, Germany), which could process stacks of tomographic scans into three-dimensional objects. Ultrahigh resolution optical coherence tomography examinations were performed on patients with various retinal pathologies and post processed with the subroutines that had been designed. All ultrahigh resolution optical coherence tomographies were performed with a titanium: sapphire based ultra broad bandwidth (160 nm) femtosecond laser system (INTEGRAL, Femtolasers Productions GmbH. Vienna Austria) with an axial resolution of 3 μm. A new three dimensional display system for tomographic images in ophthalmology was developed, which allows a highly vivid display of physiological and pathological structures of the retina. The system also distinguishes itself through its high interactivity and adaptability. This new display system allows the visualization of physiological and pathological structures of the retina in a new way, which will give us new insight into their morphology and development. (author) [de

Inner neural retina loss in central retinal artery occlusion.

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Ikeda, Fumiko; Kishi, Shoji

2010-09-01

To report morphologic retinal changes and visual outcomes in acute and chronic central retinal artery occlusion (CRAO). We reviewed ten eyes of ten patients with CRAO (age, 65.3 ± 10.2 years) and measured retinal thicknesses at the central fovea and the perifovea using optical coherence tomography (OCT) over 8 ± 4 months. During the acute phase (within 10 days), the mean inner retinal thicknesses were 148% and 139% of normal values at 1 mm nasal and temporal to the fovea. They decreased to 22% and 11% of normal inner retinal thickness during the chronic phase (3 months or later). The retinal thickness at the perifovea decreased linearly until 3 months but was stable during the chronic phase. In contrast, the foveal thickness increased slightly in the acute phase but was equivalent to the normal level during the chronic phase. As a result of inner retinal atrophy, the foveal pit was shallow during the chronic phase. The final visual acuity was correlated positively with retinal thickness at the perifovea during the chronic CRAO phase. OCT showed that inner retinal necrosis with early swelling and late atrophy occurred in CRAO. The fovea and outer retina appeared to be excluded from ischemic change. The residual inner retina at the perifovea determined the final visual outcomes.

Subthreshold transpupillary thermotherapy reduces experimental choroidal neovascularization in the mouse without collateral damage to the neural retina.

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Ming, Yue; Algvere, Peep V; Odergren, Anne; Berglin, Lennart; van der Ploeg, Ingeborg; Seregard, Stefan; Kvanta, Anders

2004-06-01

Transpupillary thermotherapy (TTT) is currently being evaluated for treatment of choroidal neovascularization (CNV) in age-related macular degeneration. To optimize TTT for CNV, the effect was analyzed of invisible (subthreshold) or visible (threshold) doses of TTT on the normal mouse retina and on experimental CNV. TTT was delivered to the normal retina of 42 mice with a diode laser at increasing power settings (50, 60, 70, or 80 mW), to obtain thermal lesions ranging from invisible (subthreshold) to visible (threshold) burns. CNV was induced in 53 mice by krypton laser photocoagulation of the fundus, after which the CNV lesions were treated with TTT (50, 60, or 80 mW). Eyes were enucleated 7 days after TTT and prepared for histology, and the CNV complex was evaluated on hematoxylin-eosin stained serial sections by measuring the maximum height of the CNV lesions. Ultrastructural changes were examined by transmission electron microscopy. Increasing the TTT laser power yielded gradually more visible effects. At 50 mW, which induced subthreshold burns, no damage was seen in the neural retina, retinal pigment epithelium (RPE), or choroid at any time point. By contrast, eyes treated with higher power exhibited progressively more damage to the neural retina, including a complete disruption of the outer nuclear layer. When TTT was applied to the laser-induced CNV lesions, the height of lesions was significantly reduced (P response to all three power settings at 7 days after treatment. The mean relative thickness of the CNV lesion was 3.29 +/- 0.89 in untreated mice, whereas in TTT-treated mice it was 1.69 +/- 0.35, 1.69 +/- 0.41 and 1.70 +/- 0.17 at power settings of 50, 60, and 80 mW, respectively. The overlying neural retina showed no apparent damage with the 50- or 60-mW settings, whereas outer nuclear layer disruption occurred with a power of 80 mW. Electron microscopy confirmed the presence of vascular occlusion at 1 day and a fibrotic scar at 7 days after TTT

Automatic and manual segmentation of healthy retinas using high-definition optical coherence tomography.

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Golbaz, Isabelle; Ahlers, Christian; Goesseringer, Nina; Stock, Geraldine; Geitzenauer, Wolfgang; Prünte, Christian; Schmidt-Erfurth, Ursula Margarethe

2011-03-01

This study compared automatic- and manual segmentation modalities in the retina of healthy eyes using high-definition optical coherence tomography (HD-OCT). Twenty retinas in 20 healthy individuals were examined using an HD-OCT system (Carl Zeiss Meditec, Inc.). Three-dimensional imaging was performed with an axial resolution of 6 μm at a maximum scanning speed of 25,000 A-scans/second. Volumes of 6 × 6 × 2 mm were scanned. Scans were analysed using a matlab-based algorithm and a manual segmentation software system (3D-Doctor). The volume values calculated by the two methods were compared. Statistical analysis revealed a high correlation between automatic and manual modes of segmentation. The automatic mode of measuring retinal volume and the corresponding three-dimensional images provided similar results to the manual segmentation procedure. Both methods were able to visualize retinal and subretinal features accurately. This study compared two methods of assessing retinal volume using HD-OCT scans in healthy retinas. Both methods were able to provide realistic volumetric data when applied to raster scan sets. Manual segmentation methods represent an adequate tool with which to control automated processes and to identify clinically relevant structures, whereas automatic procedures will be needed to obtain data in larger patient populations. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

Comparative immunolocalization of the plasma membrane calcium pump and calbindin D28K in chicken retina during embryonic development

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N. Tolosa de Talamoni

2010-05-01

Full Text Available The immunolocalization of the plasma membrane calcium pump (PMCA was studied in 4-week-old chick retina in comparison with calbindin D28K (CaBP immunostaining. We have demonstrated that the monoclonal anti-PMCA antibody 5F10 from human erythrocyte plasma membrane crossreacts with a Ca2+ pump epitope of the cells from the neural retina. The immunolocalization of both proteins was also studied during the embryonic development of the chicken retina. At age 4.5 days, the cells of the retina were faintly immunoreactive to PMCA and CaBP antibodies, but the lack of cellular aggregation and differentiation did not allow discrimination between the two proteins. A clear difference in the localization was seen from the tenth day of development through post-hatching with slight variation. PMCA localized mainly in the outer and inner plexiform layers, in some cells in the ganglion layer, in the nerve fiber layer and slightly in the photoreceptor cells. CaBP was intensely stained in cones, cone pedicles and some amacrine cells. The number of CaBP positive amacrine cells declined after hatching. A few ganglion cells and several nerve fibers were CaBP 333 immunoreactive. The role of these proteins in the early stages of retinal development is unknown, but the results suggest that Ca2+ homeostasis in the retina is well regulated, probably to avoid excessive accumulation of Ca2+, which often leads to neurodegeneration.

Localization, distribution, and connectivity of neuropeptide Y in the human and porcine retinas-A comparative study.

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Christiansen, Anders Tolstrup; Kiilgaard, Jens Folke; Klemp, Kristian; Woldbye, David Paul Drucker; Hannibal, Jens

2018-04-17

Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell-type, and connectivity has never been conducted in larger mammals including humans and pigs. As the pig due to size and cellular composition is a well-suited animal for retinal research, we chose to compare the endogenous NPY system of the human retina to that of pigs to support future research in this field. In the present study, using immunohistochemistry, confocal microscopy and 3D reconstructions, we found NPY to be expressed in GABAergic and calretinin-immunoreactive (-ir) amacrine cells of both species as well as parvalbumin-ir amacrine cells of humans. Furthermore, we identified at least two different types of medium- to wide-field NPY-ir amacrine cells. Finally, we detected likely synaptic appositions between the NPY-ir amacrine cells and melanopsin- and nonmelanopsin-ir ganglion cells, GABAergic and dopaminergic amacrine cells, rod bipolar cells, and horizontal cells, suggesting that NPY-ir cells play diverse roles in modulation of both image and non-image forming retinal signaling. These findings extend existing knowledge on NPY and NPY-expressing cells in the human and porcine retina showing a high degree of comparability. The extensive distribution and connectivity of NPY-ir cells described in the present study further highlights the potential importance of NPY signaling in retinal function. © 2018 Wiley Periodicals, Inc.

Gradient pre-emphasis to counteract first-order concomitant fields on asymmetric MRI gradient systems.

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Tao, Shengzhen; Weavers, Paul T; Trzasko, Joshua D; Shu, Yunhong; Huston, John; Lee, Seung-Kyun; Frigo, Louis M; Bernstein, Matt A

2017-06-01

To develop a gradient pre-emphasis scheme that prospectively counteracts the effects of the first-order concomitant fields for any arbitrary gradient waveform played on asymmetric gradient systems, and to demonstrate the effectiveness of this approach using a real-time implementation on a compact gradient system. After reviewing the first-order concomitant fields that are present on asymmetric gradients, we developed a generalized gradient pre-emphasis model assuming arbitrary gradient waveforms to counteract their effects. A numerically straightforward, easily implemented approximate solution to this pre-emphasis problem was derived that was compatible with the current hardware infrastructure of conventional MRI scanners for eddy current compensation. The proposed method was implemented on the gradient driver subsystem, and its real-time use was tested using a series of phantom and in vivo data acquired from two-dimensional Cartesian phase-difference, echo-planar imaging, and spiral acquisitions. The phantom and in vivo results demonstrated that unless accounted for, first-order concomitant fields introduce considerable phase estimation error into the measured data and result in images with spatially dependent blurring/distortion. The resulting artifacts were effectively prevented using the proposed gradient pre-emphasis. We have developed an efficient and effective gradient pre-emphasis framework to counteract the effects of first-order concomitant fields of asymmetric gradient systems. Magn Reson Med 77:2250-2262, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Complex computation in the retina

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Deshmukh, Nikhil Rajiv

Elucidating the general principles of computation in neural circuits is a difficult problem requiring both a tractable model circuit as well as sophisticated measurement tools. This thesis advances our understanding of complex computation in the salamander retina and its underlying circuitry and furthers the development of advanced tools to enable detailed study of neural circuits. The retina provides an ideal model system for neural circuits in general because it is capable of producing complex representations of the visual scene, and both its inputs and outputs are accessible to the experimenter. Chapter 2 describes the biophysical mechanisms that give rise to the omitted stimulus response in retinal ganglion cells described in Schwartz et al., (2007) and Schwartz and Berry, (2008). The extra response to omitted flashes is generated at the input to bipolar cells, and is separable from the characteristic latency shift of the OSR apparent in ganglion cells, which must occur downstream in the circuit. Chapter 3 characterizes the nonlinearities at the first synapse of the ON pathway in response to high contrast flashes and develops a phenomenological model that captures the effect of synaptic activation and intracellular signaling dynamics on flash responses. This work is the first attempt to model the dynamics of the poorly characterized mGluR6 transduction cascade unique to ON bipolar cells, and explains the second lobe of the biphasic flash response. Complementary to the study of neural circuits, recent advances in wafer-scale photolithography have made possible new devices to measure the electrical and mechanical properties of neurons. Chapter 4 reports a novel piezoelectric sensor that facilitates the simultaneous measurement of electrical and mechanical signals in neural tissue. This technology could reveal the relationship between the electrical activity of neurons and their local mechanical environment, which is critical to the study of mechanoreceptors

Counteracting age-related loss of skeletal muscle mass

DEFF Research Database (Denmark)

Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith

2016-01-01

Background Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges...... at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals....

Molecular Characterization of Notch1 Positive Progenitor Cells in the Developing Retina.

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Galina Dvoriantchikova

Full Text Available The oscillatory expression of Notch signaling in neural progenitors suggests that both repressors and activators of neural fate specification are expressed in the same progenitors. Since Notch1 regulates photoreceptor differentiation and contributes (together with Notch3 to ganglion cell fate specification, we hypothesized that genes encoding photoreceptor and ganglion cell fate activators would be highly expressed in Notch1 receptor-bearing (Notch1+ progenitors, directing these cells to differentiate into photoreceptors or into ganglion cells when Notch1 activity is diminished. To identify these genes, we used microarray analysis to study expression profiles of whole retinas and isolated from them Notch1+ cells at embryonic day 14 (E14 and postnatal day 0 (P0. To isolate Notch1+ cells, we utilized immunomagnetic cell separation. We also used Notch3 knockout (Notch3KO animals to evaluate the contribution of Notch3 signaling in ganglion cell differentiation. Hierarchical clustering of 6,301 differentially expressed genes showed that Notch1+ cells grouped near the same developmental stage retina cluster. At E14, we found higher expression of repressors (Notch1, Hes5 and activators (Dll3, Atoh7, Otx2 of neuronal differentiation in Notch1+ cells compared to whole retinal cell populations. At P0, Notch1, Hes5, and Dll1 expression was significantly higher in Notch1+ cells than in whole retinas. Otx2 expression was more than thirty times higher than Atoh7 expression in Notch1+ cells at P0. We also observed that retinas of wild type animals had only 14% (P < 0.05 more ganglion cells compared to Notch3KO mice. Since this number is relatively small and Notch1 has been shown to contribute to ganglion cell fate specification, we suggested that Notch1 signaling may play a more significant role in RGC development than the Notch3 signaling cascade. Finally, our findings suggest that Notch1+ progenitors--since they heavily express both pro-ganglion cell (Atoh7

Pathological alterations typical of human Tay-Sachs disease, in the retina of a deep-sea fish

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Fishelson, L.; Delarea, Yacov; Galil, Bella S.

Micrographs of retinas from the deep-sea fish Cataetyx laticeps revealed visual cells containing membranous whorls in the ellipsoids of the inner segments resulting from stretching and modifications of the mitochondria membranes and their cristae. These pathological structures seem to be homologous to the whorls observed in retinas of human carriers of Tay-Sachs disease. This disease, a genetic disorder, is found in humans and some mammals. Our findings in fish suggest that the gene responsible can be found throughout the vertebrate evolutionary tree, possibly dormant in most taxa.

Two classes of astrocytes in the adult human and pig retina in terms of their expression of high affinity NGF receptor (TrkA).

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Ruiz-Ederra, Javier; Hitchcock, Peter F; Vecino, Elena

2003-02-13

Astrocytes have been implicated in axon guidance and synaptic regeneration in the retina and these processes involve activation of the high affinity nerve growth factor receptor, known as the tyrosine kinase A (TrkA) receptor. The purpose of the present study was to characterize the expression of TrkA in astrocytes of the adult pig and human retina. To this end, sections of human and pig retinas were immunolabeled with a combination of antibodies to glial fibrillary acidic protein (GFAP) and TrkA. Our study revealed that most of the GFAP-positive cells express TrkA, whereas a rare, novel subpopulation of astrocytes was found to be devoid of TrkA. Our results support the idea that astrocytes play an important neurotrophic role in the retina.

An artificial retina processor for track reconstruction at the LHC crossing rate

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Bedeschi, F.; Cenci, R.; Marino, P.; Morello, M. J.; Ninci, D.; Piucci, A.; Punzi, G.; Ristori, L.; Spinella, F.; Stracka, S.; Tonelli, D.; Walsh, J.

2017-10-01

The goal of the INFN-RETINA R&D project is to develop and implement a computational methodology that allows to reconstruct events with a large number (> 100) of charged-particle tracks in pixel and silicon strip detectors at 40 MHz, thus matching the requirements for processing LHC events at the full bunch-crossing frequency. Our approach relies on a parallel pattern-recognition algorithm, dubbed artificial retina, inspired by the early stages of image processing by the brain. In order to demonstrate that a track-processing system based on this algorithm is feasible, we built a sizable prototype of a tracking processor tuned to 3 000 patterns, based on already existing readout boards equipped with Altera Stratix III FPGAs. The detailed geometry and charged-particle activity of a large tracking detector currently in operation are used to assess its performances. We report on the test results with such a prototype.

Sonic hedgehog promotes stem-cell potential of Mueller glia in the mammalian retina

International Nuclear Information System (INIS)

Wan Jin; Zheng Hua; Xiao Honglei; She Zhenjue; Zhou Guomin

2007-01-01

Mueller glia have been demonstrated to display stem-cell properties after retinal damage. Here, we report this potential can be regulated by Sonic hedgehog (Shh) signaling. Shh can stimulate proliferation of Mueller glia through its receptor and target gene expressed on them, furthermore, Shh-treated Mueller glia are induced to dedifferentiate by expressing progenitor-specific markers, and then adopt cell fate of rod photoreceptor. Inhibition of signaling by cyclopamine inhibits proliferation and dedifferentiation. Intraocular injection of Shh promotes Mueller glia activation in the photoreceptor-damaged retina, Shh also enhances neurogenic potential by producing more rhodopsin-positive photoreceptors from Mueller glia-derived cells. Together, these results provide evidences that Mueller glia act as potential stem cells in mammalian retina, Shh may have therapeutic effects on these cells for promoting the regeneration of retinal neurons

Sonic hedgehog promotes stem-cell potential of Mueller glia in the mammalian retina

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Jin, Wan; Hua, Zheng; Honglei, Xiao; Zhenjue, She [Department of Anatomy, Histology and Embryology, Shanghai Medical School, Fudan University, 200032 Shanghai (China); Zhou Guomin [Department of Anatomy, Histology and Embryology, Shanghai Medical School, Fudan University, 200032 Shanghai (China)], E-mail: gmzhou185@yahoo.com.cn

2007-11-16

Mueller glia have been demonstrated to display stem-cell properties after retinal damage. Here, we report this potential can be regulated by Sonic hedgehog (Shh) signaling. Shh can stimulate proliferation of Mueller glia through its receptor and target gene expressed on them, furthermore, Shh-treated Mueller glia are induced to dedifferentiate by expressing progenitor-specific markers, and then adopt cell fate of rod photoreceptor. Inhibition of signaling by cyclopamine inhibits proliferation and dedifferentiation. Intraocular injection of Shh promotes Mueller glia activation in the photoreceptor-damaged retina, Shh also enhances neurogenic potential by producing more rhodopsin-positive photoreceptors from Mueller glia-derived cells. Together, these results provide evidences that Mueller glia act as potential stem cells in mammalian retina, Shh may have therapeutic effects on these cells for promoting the regeneration of retinal neurons.

Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

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Katrin Hanken

2016-09-01

Full Text Available Background: Fatigue in multiple sclerosis (MS patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1,5mA was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20min of a 40min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5mA over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. TDCS was delivered for 20min before patients performed a 20min lasting visual vigilance task.Results: Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in reaction time associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation.Conclusions: Anodal tDCS over the right parietal cortex can counteract the increase in reaction times during vigilance performance but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation.

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Hanken, Katrin; Bosse, Mona; Möhrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

2016-01-01

Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20 min of a 40-min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS was delivered for 20 min before patients performed a 20-min lasting visual vigilance task. Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in RT associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Anodal tDCS over the right parietal cortex can counteract the increase in RTs during vigilance performance, but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

Expression of neurotransmitters and neurotrophins in neurogenic inflammation of the rat retina

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E Bronzetti

2009-08-01

Full Text Available Antidromic stimulation of the rat trigeminal ganglion triggers the release of substance P (SP and calcitonin gene-related peptide (CGRP from sensory nerve terminals of the capsaicin sensitive C-fibers. These pro-inflammatory neuropeptides produce a marked hyperemia in the anterior segment of the eye, accompanied by increased intraocular pressure, breakdown of the blood-aqueous barrier and myosis. To assess the effects of neurogenic inflammation on the retina, specifically on the immunostaining of neurotransmitters and neurotrophins, as well as on the expression of neurotrophin receptors in the retina. RT-PCR was also accomplished in control and stimulated animals to confirm the immunohistochemical results. In the electrically stimulated eyes, immunostaining for SP, CGRP, VIP and nNOS demonstrated a marked increase in the RPE/POS (Retinal Pigment Epithelium/Photoreceptor Outer Segments, in the inner and outer granular layers and in the ganglion cells in comparison to the control eyes. CGRP and SP were found increased in stimulated animals and this result has been confirmed by RT- PCR. Changes in neurotrophin immunostaining and in receptor expression were also observed after electric stimulation of trigeminal ganglia. Decrease of BDNF and NT4 in the outer and inner layers and in ganglion cells was particularly marked. In stimulated rat retinas immunostaining and RT-PCR showed a NGF expression increase. Neurotrophin receptors remained substantially unchanged. These studies demonstrated, for the first time, that antidromic stimulation of the trigeminal ganglion and subsequent neurogenic inflammation affect immunostaining of retinal cell neurotransmitter/ neuropeptides and neurotrophins as well as the expression of neurotrophin receptors.

Vision drives correlated activity without patterned spontaneous activity in developing Xenopus retina.

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Demas, James A; Payne, Hannah; Cline, Hollis T

2012-04-01

Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABA(A) receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement. Copyright © 2011 Wiley Periodicals, Inc.

Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina.

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Tan, Shi Z; Mullard, Graham; Hollywood, Katherine A; Dunn, Warwick B; Bishop, Paul N

2016-08-01

Time-dependent post-mortem biochemical changes have been demonstrated in donor cornea and vitreous, but there have been no published studies to date that objectively measure post-mortem changes in the retinal metabolome over time. The aim of the study was firstly, to investigate post-mortem, time-dependent changes in the rat retinal metabolome and secondly, to compare the metabolite composition of healthy rat ocular tissues. To study post-mortem changes in the rat retinal metabolome, globes were enucleated and stored at 4 °C and sampled at 0, 2, 4, 8, 24 and 48 h post-mortem. To study the metabolite composition of rat ocular tissues, eyes were dissected immediately after culling to isolate the cornea, lens, vitreous and retina, prior to storing at -80 °C. Tissue extracts were subjected to Gas Chromatograph Mass Spectrometry (GC-MS) and Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS). Generally, the metabolic composition of the retina was stable for 8 h post-mortem when eyes were stored at 4 °C, but showed increasing changes thereafter. However, some more rapid changes were observed such as increases in TCA cycle metabolites after 2 h post-mortem, whereas some metabolites such as fatty acids only showed decreases in concentration from 24 h. A total of 42 metabolites were identified across the ocular tissues by GC-MS (MSI level 1) and 2782 metabolites were annotated by UHPLC-MS (MSI level 2) according to MSI reporting standards. Many of the metabolites detected were common to all of the tissues but some metabolites showed partitioning between different ocular structures with 655, 297, 93 and 13 metabolites being uniquely detected in the retina, lens, cornea and vitreous respectively. Only a small percentage (1.6%) of metabolites found in the vitreous were only detected in the retina and not other tissues. In conclusion, mass spectrometry-based techniques have been used for the first time to compare the metabolic composition of

Localisation of the Putative Magnetoreceptive Protein Cryptochrome 1b in the Retinae of Migratory Birds and Homing Pigeons.

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Petra Bolte

Full Text Available Cryptochromes are ubiquitously expressed in various animal tissues including the retina. Some cryptochromes are involved in regulating circadian activity. Cryptochrome proteins have also been suggested to mediate the primary mechanism in light-dependent magnetic compass orientation in birds. Cryptochrome 1b (Cry1b exhibits a unique carboxy terminus exclusively found in birds so far, which might be indicative for a specialised function. Cryptochrome 1a (Cry1a is so far the only cryptochrome protein that has been localised to specific cell types within the retina of migratory birds. Here we show that Cry1b, an alternative splice variant of Cry1a, is also expressed in the retina of migratory birds, but it is primarily located in other cell types than Cry1a. This could suggest different functions for the two splice products. Using diagnostic bird-specific antibodies (that allow for a precise discrimination between both proteins, we show that Cry1b protein is found in the retinae of migratory European robins (Erithacus rubecula, migratory Northern Wheatears (Oenanthe oenanthe and pigeons (Columba livia. In all three species, retinal Cry1b is localised in cell types which have been discussed as potentially well suited locations for magnetoreception: Cry1b is observed in the cytosol of ganglion cells, displaced ganglion cells, and in photoreceptor inner segments. The cytosolic rather than nucleic location of Cry1b in the retina reported here speaks against a circadian clock regulatory function of Cry1b and it allows for the possible involvement of Cry1b in a radical-pair-based magnetoreception mechanism.

Using induced pluripotent stem cell-derived conditional medium to attenuate the light-induced photodamaged retina of rats

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Hua-Ming Chang

2015-03-01

Conclusion: The conditional medium of iPSCs contains plenty of cytoprotective, immune-modulative and rescue chemicals, contributing to the maintenance of neuronal function and retinal layers in light-damaged retina compared with apoptotic iPSC-CM and PBS. The antiapoptotic effect of iPSC-CM also shows promise in restoring damaged neurons. This result demonstrates that iPSC-CM may serve as an alternative to cell therapy alone to treat retinal light damage and maintain functional and structural integrity of the retina.

The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina.

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Young, T L; Matsuda, T; Cepko, C L

2005-03-29

With the advent of genome-wide analyses, it is becoming evident that a large number of noncoding RNAs (ncRNAs) are expressed in vertebrates. However, of the thousands of ncRNAs identified, the functions of relatively few have been established. In a screen for genes upregulated by taurine in developing retinal cells, we identified a gene that appears to be a ncRNA. Taurine Upregulated Gene 1 (TUG1) is a spliced, polyadenylated RNA that does not encode any open reading frame greater than 82 amino acids in its full-length, 6.7 kilobase (kb) RNA sequence. Analyses of Northern blots and in situ hybridization revealed that TUG1 is expressed in the developing retina and brain, as well as in adult tissues. In the newborn retina, knockdown of TUG1 with RNA interference (RNAi) resulted in malformed or nonexistent outer segments of transfected photoreceptors. Immunofluorescent staining and microarray analyses suggested that this loss of proper photoreceptor differentiation is a result of the disregulation of photoreceptor gene expression. A function for a newly identified ncRNA, TUG1, has been established. TUG1 is necessary for the proper formation of photoreceptors in the developing rodent retina.

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

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Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

1988-01-01

We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

Peripheral Avascular Retina in a Term Male Neonate With Microvillus Inclusion Disease and Pancreatic Insufficiency.

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Paulus, Yannis M; Alcorn, Deborah M; Gaynon, Michael; Moshfeghi, Darius M

2015-05-01

The authors present the first case of peripheral avascular retina in a term male neonate with pancreatic exocrine insufficiency, atypical microvillus inclusion disease, flat tympanograms, and recurrent urinary tract infections. Clinical examination showed avascular peripheral retina to posterior zone II temporally, with a flat stage 1-like demarcation line, and no plus disease. Genetic testing results were normal. The patient developed peripheral neovascularization and underwent panretinal photocoagulation. This case likely represents mild Norrie disease, familial exudative vitreoretinopathy, or incontinentia pigmenti due to a Wnt signaling abnormality. While these conditions are usually more severe, a variable spectrum of Wnt abnormalities exists throughout the body. Copyright 2015, SLACK Incorporated.

Simultaneous optical coherence tomography and lipofuscin autofluorescence imaging of the retina with a single broadband light source at 480nm.

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Jiang, Minshan; Liu, Tan; Liu, Xiaojing; Jiao, Shuliang

2014-12-01

We accomplished spectral domain optical coherence tomography and auto-fluorescence microscopy for imaging the retina with a single broadband light source centered at 480 nm. This technique is able to provide simultaneous structural imaging and lipofuscin molecular contrast of the retina. Since the two imaging modalities are provided by the same group of photons, their images are intrinsically registered. To test the capabilities of the technique we periodically imaged the retinas of the same rats for four weeks. The images successfully demonstrated lipofuscin accumulation in the retinal pigment epithelium with aging. The experimental results showed that the dual-modal imaging system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

Survey of intravitreal injection techniques among retina specialists in Israel

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Segal O

2016-06-01

Full Text Available Ori Segal,1,2 Yael Segal-Trivitz,1,3 Arie Y Nemet,1,2 Noa Geffen,1,2 Ronit Nesher,1,2 Michael Mimouni4 1Department of Ophthalmology, Meir Medical Center, Kfar Saba, 2The Sackler School of Medicine, Tel Aviv University, Tel Aviv, 3Department of Psychiatry, Geha Psychiatric Hospital, Petah Tikva, 4Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel Purpose: The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines. Methods: All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques. Results: Overall, 66% (52/79 completed the survey. Most (98% do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71% use sterile surgical draping. All respondents apply topical analgesics and a majority (69% measure the distance from the limbus to the injection site. A minority (21% displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%. Less than half routinely assess postinjection optic nerve perfusion (44%. A majority (92% apply prophylactic antibiotics immediately after the injection. Conclusion: The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques

Distribution of FMRFamide-like immunoreactivity in the brain, retina and nervus terminalis of the sockeye salmon parr, Oncorhynchus nerka.

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Ostholm, T; Ekström, P; Ebbesson, S O

1990-09-01

Neurons displaying FMRFamide(Phe - Met - Arg - Phe - NH2)-like immunoreactivity have recently been implicated in neural plasticity in salmon. We now extend these findings by describing the extent of the FMRF-like immunoreactive (FMRF-IR) system in the brain, retina and olfactory system of sockeye salmon parr using the indirect peroxidase anti-peroxidase technique. FMRF-IR perikarya were found in the periventricular hypothalamus, mesencephalic laminar nucleus, nucleus nervi terminalis and retina (presumed amacrine cells), and along the olfactory nerves. FMRF-IR fibers were distributed throughout the brain with highest densities in the ventral area of the telencephalon, in the medial forebrain bundle, and at the borders between layers III/IV and IV/V in the optic tectum. High densities of immunoreactive fibers were also observed in the area around the torus semicircularis, in the medial hypothalamus, median raphe, ventromedial tegmentum, and central gray. In the retina, immunopositive fibers were localized to the inner plexiform layer, but several fiber elements were also found in the outer plexiform layer. The olfactory system displayed FMRF-IR fibers in the epithelium and along the olfactory nerves. These findings differ from those reported in other species as follows: (i) FMRF-IR cells in the retina have not previously been reported in teleosts; (ii) the presence of FMRF-IR fibers in the outer plexiform layer of the retina is a new finding for any species; (iii) the occurrence of immunopositive cells in the mesencephalic laminar nucleus has to our knowledge not been demonstrated previously.

Modulation of horizontal cell receptive fields in the light adapted goldfish retina

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Verweij, J.; Kamermans, M.; van den Aker, E. C.; Spekreijse, H.

1996-01-01

In the isolated goldfish retina, 700 nm background illumination increases the horizontal cell receptive field size, as measured with 565 nm slits of light, but decreases the receptive field size, when measured with 660 nm slits. These background-induced changes in receptive field size are absent

Non-mydriatic video ophthalmoscope to measure fast temporal changes of the human retina

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Tornow, Ralf P.; Kolář, Radim; Odstrčilík, Jan

2015-07-01

The analysis of fast temporal changes of the human retina can be used to get insight to normal physiological behavior and to detect pathological deviations. This can be important for the early detection of glaucoma and other eye diseases. We developed a small, lightweight, USB powered video ophthalmoscope that allows taking video sequences of the human retina with at least 25 frames per second without dilating the pupil. Short sequences (about 10 s) of the optic nerve head (20° x 15°) are recorded from subjects and registered offline using two-stage process (phase correlation and Lucas-Kanade approach) to compensate for eye movements. From registered video sequences, different parameters can be calculated. Two applications are described here: measurement of (i) cardiac cycle induced pulsatile reflection changes and (ii) eye movements and fixation pattern. Cardiac cycle induced pulsatile reflection changes are caused by changing blood volume in the retina. Waveform and pulse parameters like amplitude and rise time can be measured in any selected areas within the retinal image. Fixation pattern ΔY(ΔX) can be assessed from eye movements during video acquisition. The eye movements ΔX[t], ΔY[t] are derived from image registration results with high temporal (40 ms) and spatial (1,86 arcmin) resolution. Parameters of pulsatile reflection changes and fixation pattern can be affected in beginning glaucoma and the method described here may support early detection of glaucoma and other eye disease.

The area centralis in the chicken retina contains efferent target amacrine cells

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Weller, Cynthia; Lindstrom, Sarah H.; De Grip, Willem J.; Wilson, Martin

2012-01-01

The retinas of birds receive a substantial efferent, or centrifugal, input from a midbrain nucleus. The function of this input is presently unclear but previous work in the pigeon has shown that efferent input is excluded from the area centralis, suggesting that the functions of the area centralis and the efferent system are incompatible. Using an antibody specific to rods, we have identified the area centralis in another species, the chicken, and mapped the distribution of the unique amacrine cells that are the postsynaptic partners of efferent fibers. Efferent target amacrine cells are found within the chicken area centralis and their density is continuous across the border of the area centralis. In contrast to the pigeon retina then, we conclude that the chicken area centralis receives efferent input. We suggest that the difference between the 2 species is attributable to the presence of a fovea within the area centralis of the pigeon and its absence from that of the chicken. PMID:19296862

Protective effect of melatonin in the diabetic rat retina.

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Mehrzadi, Saeed; Motevalian, Manijeh; Rezaei Kanavi, Mozhgan; Fatemi, Iman; Ghaznavi, Habib; Shahriari, Mansoor

2018-03-01

Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes. The aim of this study was to evaluate the effects of melatonin (MEL) on retinal injury in diabetic rats. In this study, 21 rats were randomly divided into three groups: control, diabetic, and diabetic + MEL. Streptozotocin was used to induce diabetes at a dose of 50 mg/kg, i.p., and blood glucose was measured to choose the diabetic rats for the study. MEL (20 mg/kg) was given orally for 7 weeks in diabetic rats starting 1 week after induction of diabetes. After 8 weeks, the groups were compared in terms of mean scores of fluorescein leakage, using fluorescein angiography. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were estimated in retina using commercially available assays. Structural changes in retinas were evaluated by light microscopy. Results showed that diabetes significantly increased the mean scores of fluorescein leakage, and MDA and ROS levels compared to control group. Treatment of the diabetic rats with MEL for 7 weeks prevented the alterations induced by diabetes in comparison with the diabetic control group.Based on these findings, it can be concluded that MEL might have beneficial effects in prevention of DR. © 2018 Société Française de Pharmacologie et de Thérapeutique.

Temporal resolution of misfolded prion protein transport, accumulation, glial activation, and neuronal death in the retinas of mice inoculated with scrapie

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Currently, there is a lack of pathologic landmarks to describe the progression of prion disease in vivo. The goal of this work was to determine the temporal relationship between the transport of misfolded prion protein from the brain to the retina, the accumulation of PrPSc in the retina, the respon...

Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina

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Bibliowicz Jonathan

2009-10-01

Full Text Available Abstract Background The roles of the Hedgehog (Hh pathway in controlling vertebrate retinal development have been studied extensively; however, species- and context-dependent findings have provided differing conclusions. Hh signaling has been shown to control both population size and cell cycle kinetics of proliferating retinal progenitors, and to modulate differentiation within the retina by regulating the timing of cell cycle exit. While cell cycle exit has in turn been shown to control cell fate decisions within the retina, a direct role for the Hh pathway in retinal cell fate decisions has yet to be established in vivo. Results To gain further insight into Hh pathway function in the retina, we have analyzed retinal development in leprechaun/patched2 mutant zebrafish. While lep/ptc2 mutants possessed more cells in their retinas, all cell types, except for Müller glia, were present at identical ratios as those observed in wild-type siblings. lep/ptc2 mutants possessed a localized upregulation of GFAP, a marker for 'reactive' glia, as well as morphological abnormalities at the vitreo-retinal interface, where Müller glial endfeet terminate. In addition, analysis of the over-proliferation phenotype at the ciliary marginal zone (CMZ revealed that the number of proliferating progenitors, but not the rate of proliferation, was increased in lep/ptc2 mutants. Conclusion Our results indicate that Patched2-dependent Hh signaling does not likely play an integral role in neuronal cell fate decisions in the zebrafish retina. ptc2 deficiency in zebrafish results in defects at the vitreo-retinal interface and Müller glial reactivity. These phenotypes are similar to the ocular abnormalities observed in human patients suffering from Basal Cell Naevus Syndrome (BCNS, a disorder that has been linked to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2, and point to the utility of the lep/ptc2 mutant line as a model for the study of BCNS

ISG15 counteracts Listeria monocytogenes infection

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Radoshevich, Lilliana; Impens, Francis; Ribet, David; Quereda, Juan J; Nam Tham, To; Nahori, Marie-Anne; Bierne, Hélène; Dussurget, Olivier; Pizarro-Cerdá, Javier; Knobeloch, Klaus-Peter; Cossart, Pascale

2015-01-01

ISG15 is an interferon-stimulated, linear di-ubiquitin-like protein, with anti-viral activity. The role of ISG15 during bacterial infection remains elusive. We show that ISG15 expression in nonphagocytic cells is dramatically induced upon Listeria infection. Surprisingly this induction can be type I interferon independent and depends on the cytosolic surveillance pathway, which senses bacterial DNA and signals through STING, TBK1, IRF3 and IRF7. Most importantly, we observed that ISG15 expression restricts Listeria infection in vitro and in vivo. We made use of stable isotope labeling in tissue culture (SILAC) to identify ISGylated proteins that could be responsible for the protective effect. Strikingly, infection or overexpression of ISG15 leads to ISGylation of ER and Golgi proteins, which correlates with increased secretion of cytokines known to counteract infection. Together, our data reveal a previously uncharacterized ISG15-dependent restriction of Listeria infection, reinforcing the view that ISG15 is a key component of the innate immune response. DOI: http://dx.doi.org/10.7554/eLife.06848.001 PMID:26259872

Unidirectional photoreceptor-to-Müller glia coupling and unique K+ channel expression in Caiman retina.

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Astrid Zayas-Santiago

Full Text Available Müller cells, the principal glial cells of the vertebrate retina, are fundamental for the maintenance and function of neuronal cells. In most vertebrates, including humans, Müller cells abundantly express Kir4.1 inwardly rectifying potassium channels responsible for hyperpolarized membrane potential and for various vital functions such as potassium buffering and glutamate clearance; inter-species differences in Kir4.1 expression were, however, observed. Localization and function of potassium channels in Müller cells from the retina of crocodiles remain, hitherto, unknown.We studied retinae of the Spectacled caiman (Caiman crocodilus fuscus, endowed with both diurnal and nocturnal vision, by (i immunohistochemistry, (ii whole-cell voltage-clamp, and (iii fluorescent dye tracing to investigate K+ channel distribution and glia-to-neuron communications.Immunohistochemistry revealed that caiman Müller cells, similarly to other vertebrates, express vimentin, GFAP, S100β, and glutamine synthetase. In contrast, Kir4.1 channel protein was not found in Müller cells but was localized in photoreceptor cells. Instead, 2P-domain TASK-1 channels were expressed in Müller cells. Electrophysiological properties of enzymatically dissociated Müller cells without photoreceptors and isolated Müller cells with adhering photoreceptors were significantly different. This suggests ion coupling between Müller cells and photoreceptors in the caiman retina. Sulforhodamine-B injected into cones permeated to adhering Müller cells thus revealing a uni-directional dye coupling.Our data indicate that caiman Müller glial cells are unique among vertebrates studied so far by predominantly expressing TASK-1 rather than Kir4.1 K+ channels and by bi-directional ion and uni-directional dye coupling to photoreceptor cells. This coupling may play an important role in specific glia-neuron signaling pathways and in a new type of K+ buffering.

Expression and Localization of TRK-Fused Gene Products in the Rat Brain and Retina

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Maebayashi, Hisae; Takeuchi, Shigako; Masuda, Chiaki; Makino, Satoshi; Fukui, Kenji; Kimura, Hiroshi; Tooyama, Ikuo

2012-01-01

The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It has been reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. However, no information regarding the localization of Tfg in rat tissues is available. In this study, we investigated the expression of Tfg mRNA in normal rat tissues using reverse transcription-polymerase chain reaction (RT-PCR). We also produced an antibody against Tfg gene products and examined the localization of TFG in the rat brain and retina. The RT-PCR experiments demonstrated that two types of Tfg mRNA were expressed in rat tissues: the conventional form of Tfg (cTfg) and a novel variant form, retinal Tfg (rTfg). RT-PCR analyses demonstrated that cTfg was ubiquitously expressed in rat tissues, while rTfg was predominantly expressed in the brain and retina. Western blot analysis demonstrated two bands with molecular weights of about 30 kDa and 50 kDa in the rat brain. Immunohistochemistry indicated that TFG proteins were predominantly expressed by neurons in the brain. In the rat retina, intense TFG-immunoreactivity was detected in the layer of rods and cones and the outer plexiform layer

Coherent anti-stokes Raman scattering (CARS) microscopy: a novel technique for imaging the retina.

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Masihzadeh, Omid; Ammar, David A; Kahook, Malik Y; Lei, Tim C

2013-05-01

To image the cellular and noncellular structures of the retina in an intact mouse eye without the application of exogenous fluorescent labels using noninvasive, nondestructive techniques. Freshly enucleated mouse eyes were imaged using two nonlinear optical techniques: coherent anti-Stokes Raman scattering (CARS) and two-photon autofluorescence (TPAF). Cross sectional transverse sections and sequential flat (en face) sagittal sections were collected from a region of sclera approximately midway between the limbus and optic nerve. Imaging proceeded from the surface of the sclera to a depth of ∼60 μm. The fluorescent signal from collagen fibers within the sclera was evident in the TPAF channel; the scleral collagen fibers showed no organization and appeared randomly packed. The sclera contained regions lacking TPAF and CARS fluorescence of ∼3 to 15 μm in diameter that could represent small vessels or scleral fibroblasts. Intense punctate CARS signals from the retinal pigment epithelial layer were of a size and shape of retinyl storage esters. Rod outer segments could be identified by the CARS signal from their lipid-rich plasma membranes. CARS microscopy can be used to image the outer regions of the mammalian retina without the use of a fluorescent dye or exogenously expressed recombinant protein. With technical advancements, CARS/TPAF may represent a new avenue for noninvasively imaging the retina and might complement modalities currently used in clinical practice.

Immunocytochemical localization of the glutamate transporter GLT-1 in goldfish (Carassius auratus) retina

NARCIS (Netherlands)

Vandenbranden, C. A.; Yazulla, S.; Studholme, K. M.; Kamphuis, W.; Kamermans, M.

2000-01-01

Glutamate is the major excitatory neurotransmitter in the retina of vertebrates. Electrophysiological experiments in goldfish and salamander have shown that neuronal glutamate transporters play an important role in the clearance of glutamate from cone synaptic clefts. In this study, the localization

Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum.

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Uesaka, Naofumi; Abe, Manabu; Konno, Kohtarou; Yamazaki, Maya; Sakoori, Kazuto; Watanabe, Takaki; Kao, Tzu-Huei; Mikuni, Takayasu; Watanabe, Masahiko; Sakimura, Kenji; Kano, Masanobu

2018-02-21

Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16. Progranulin derived from PCs acts retrogradely onto its putative receptor Sort1 on CFs. This effect is independent of semaphorin 3A, another retrograde signaling molecule that counteracts CF synapse elimination. We propose that progranulin-Sort1 signaling strengthens and maintains developing CF inputs, and may contribute to selection of single "winner" CFs that survive synapse elimination. Copyright © 2018 Elsevier Inc. All rights reserved.

Retina damage after exposure to UVA radiation on the early developmental stages of the Egyptian toad Bufo regularis Reuss

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Alaa El-Din H. Sayed

2016-10-01

Full Text Available The present study was carried out to investigate the histological and histochemical changes in the retina on different developmental stages of Egyptian toad Bufo regularis. Our experiment started when tadpoles begin to feed. The adapted embryos are divided into 3 large tanks of 200 embryos each, collections of samples started from feeding age every three days. Both histological and histochemical results showed that the general architecture of the retina organ is correlated with the state of development. Therefore, it displayed different characteristic features depending on the investigated developmental stage starting from the larval stage (feeding began, stage 44 and ending with the post-metamorphic stage 66. Also, the present work aimed to study the chronic effects of UVA on the retina structure of B. regularis during development and metamorphosis for the first time.

Synaptic Mechanisms Generating Orientation Selectivity in the ON Pathway of the Rabbit Retina.

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Venkataramani, Sowmya; Taylor, W Rowland

2016-03-16

Neurons that signal the orientation of edges within the visual field have been widely studied in primary visual cortex. Much less is known about the mechanisms of orientation selectivity that arise earlier in the visual stream. Here we examine the synaptic and morphological properties of a subtype of orientation-selective ganglion cell in the rabbit retina. The receptive field has an excitatory ON center, flanked by excitatory OFF regions, a structure similar to simple cell receptive fields in primary visual cortex. Examination of the light-evoked postsynaptic currents in these ON-type orientation-selective ganglion cells (ON-OSGCs) reveals that synaptic input is mediated almost exclusively through the ON pathway. Orientation selectivity is generated by larger excitation for preferred relative to orthogonal stimuli, and conversely larger inhibition for orthogonal relative to preferred stimuli. Excitatory orientation selectivity arises in part from the morphology of the dendritic arbors. Blocking GABAA receptors reduces orientation selectivity of the inhibitory synaptic inputs and the spiking responses. Negative contrast stimuli in the flanking regions produce orientation-selective excitation in part by disinhibition of a tonic NMDA receptor-mediated input arising from ON bipolar cells. Comparison with earlier studies of OFF-type OSGCs indicates that diverse synaptic circuits have evolved in the retina to detect the orientation of edges in the visual input. A core goal for visual neuroscientists is to understand how neural circuits at each stage of the visual system extract and encode features from the visual scene. This study documents a novel type of orientation-selective ganglion cell in the retina and shows that the receptive field structure is remarkably similar to that of simple cells in primary visual cortex. However, the data indicate that, unlike in the cortex, orientation selectivity in the retina depends on the activity of inhibitory interneurons. The

Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

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Yan Lu

2014-02-01

Full Text Available AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab, respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05, while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05. Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05 in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05 in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05. The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05. No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

Vsx2 in the zebrafish retina: restricted lineages through derepression

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Higashijima Shin-ichi

2009-04-01

Full Text Available Abstract Background The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs. It is not clear, however, which progenitors are multipotent or why they are multipotent. Results In this study we show that the homeodomain transcription factor Vsx2 is initially expressed throughout the retinal epithelium, but later it is downregulated in all but a minor population of bipolar cells and all Müller glia. The Vsx2-negative daughters of Vsx2-positive RPCs divide and give rise to all other cell types in the retina. Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates. Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2. Conclusion Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.

Müller Glial Cell-Provided Cellular Light Guidance through the Vital Guinea-Pig Retina

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Agte, Silke; Junek, Stephan; Matthias, Sabrina; Ulbricht, Elke; Erdmann, Ines; Wurm, Antje; Schild, Detlev; Käs, Josef A.; Reichenbach, Andreas

2011-01-01

In vertebrate eyes, images are projected onto an inverted retina where light passes all retinal layers on its way to the photoreceptor cells. Light scattering within this tissue should impair vision. We show that radial glial (Müller) cells in the living retina minimize intraretinal light scatter and conserve the diameter of a beam that hits a single Müller cell endfoot. Thus, light arrives at individual photoreceptors with high intensity. This leads to an optimized signal/noise ratio, which increases visual sensitivity and contrast. Moreover, we show that the ratio between Müller cells and cones—responsible for acute vision—is roughly 1. This suggests that high spatiotemporal resolution may be achieved by each cone receiving its part of the image via its individual Müller cell-light guide. PMID:22261048

Zinc might protect oxidative changes in the retina and pancreas at the early stage of diabetic rats

International Nuclear Information System (INIS)

Moustafa, Sohair A.

2004-01-01

It is well documented that oxidative stress is a basic mechanism behind the development of diabetic retinopathy (DR). The current study was undertaken to elucidate the possible role of zinc as an antioxidant and a biological membrane stabilizer in the protection against (DR). Male Wistar rats weighing 250 ± 50 g were made diabetic by injection with a single ip dose of alloxan (100 mg/kg). Another group of rats was simultaneously treated with alloxan (100 mg/kg) and a single ip dose of zinc chloride (ZnCl 2 ) (5 mg/kg). Blood and tissue samples were collected at 24, 48, and 72 h post-treatment in both groups. Diabetic state was confirmed by the determination of plasma glucose levels (significantly elevated at any time of the experiment when compared with controls receiving vehicle). Plasma insulin was significantly increased 24 h after treatment in both alloxan and alloxan plus ZnCl 2 -treated groups, and then decreased markedly 48 and 72 h post treatment in both groups. Alloxan treatment depleted both retinal and liver glutathione contents. The decrease in retinal and liver GSH in alloxan-treated rats was accompanied with a sustained increase in their thiobarbituric acid (TBA) content. Simultaneous treatment of rats with alloxan and ZnCl 2 blunted the sustained increment in plasma glucose induced by alloxan. The combined administration of alloxan and zinc reversed the depleting effect on retinal and hepatic GSH in alloxan-treated rats and reduced the elevations in TBA content of both retinas and livers. At variance with many other antioxidants the current results clearly indicate the beneficial effects of Zn in both controlling hyperglycemia and the protection of the retina against oxidative stress in diabetes which may help set a new direction toward the development of effective treatments of DR

Responsibility of the administration and control by the courts

International Nuclear Information System (INIS)

Papier, H.J.

1987-01-01

This contribution examines the scope of control of the administrative courts by closer looking at the field of tension between the demand for more protection of the individual's right, and for more indicial control on the other hand. One proposal for solving the problem is that the legislature might restrict judicial control to watching over the principle of justifiability, and there are other suggestions discussed that seek solutions in the field of procedural law, or substantive law. Other aspects discussed include a curtailment of the scope of discretion of authorities, or of local governments. As for years now there hasn't been any nuclear power plant that could start operation on the basis of uncontested licences, the administrative legal protection in this field seems to be disfunctional. The courts themselves can contribute a lot to preventing disfunctionality, but the legislature is mainly responsible for this development, and should be the first to counteract. (HSCH) [de

Inhibition of non-neuronal cell proliferation in the goldfish visual pathway affects the regenerative capacity of the retina

International Nuclear Information System (INIS)

Neuman, D.; Yerushalmi, A.; Schwartz, M.

1983-01-01

Proliferating cells associated with the visual pathway were found in the present study of affect the regenerative capacity of the goldfish retina following optic nerve injury. The contribution of these cells to the process of regeneration was investigated in the goldfish visual system by reducing their proliferation in the optic tract and tecta, using X-irradiation. The regenerative ability of the retina was then evaluated by the following parameters: sprouting from retinal explants, protein synthesis in the retina and accumulation of radiolabeled transported components in the tectum. X-irradiation of the visual system at an early stage of the regeneration process had a promoting effect whereas irradiation at a later stage resulted in a reduced capacity to regenerate. The results are discussed with respect to the possibility that proliferating cells, possibly glia, exert two contradictory contributions: an inhibitory effect at the site of injury, whereas distal to it, a supportive, perhaps trophic effect. (Auth.)

Inhibition of non-neuronal cell proliferation in the goldfish visual pathway affects the regenerative capacity of the retina

Energy Technology Data Exchange (ETDEWEB)

Neuman, D.; Yerushalmi, A.; Schwartz, M. (Weizmann Inst. of Science, Rehovoth (Israel))

1983-08-08

Proliferating cells associated with the visual pathway were found in the present study of affect the regenerative capacity of the goldfish retina following optic nerve injury. The contribution of these cells to the process of regeneration was investigated in the goldfish visual system by reducing their proliferation in the optic tract and tecta, using X-irradiation. The regenerative ability of the retina was then evaluated by the following parameters: sprouting from retinal explants, protein synthesis in the retina and accumulation of radiolabeled transported components in the tectum. X-irradiation of the visual system at an early stage of the regeneration process had a promoting effect whereas irradiation at a later stage resulted in a reduced capacity to regenerate. The results are discussed with respect to the possibility that proliferating cells, possibly glia, exert two contradictory contributions: an inhibitory effect at the site of injury, whereas distal to it, a supportive, perhaps trophic effect.

Modified saponification and HPLC methods for analyzing carotenoids from the retina of quail: implications for its use as a nonprimate model species.

Science.gov (United States)

Toomey, Matthew B; McGraw, Kevin J

2007-09-01

To investigate carotenoid content in the retina of Japanese quail (Coturnix japonica), for comparison with carotenoids in human retina, and to assess the effects of different saponification procedures on the recovery of quail retinal carotenoids. Extracted retinal carotenoids were saponified with methods adapted from recent studies, then identified and quantified with reverse-phase high-performance liquid chromatography (HPLC). To assess the effects of saponification conditions on carotenoid recovery from quail retina, we varied base concentration and the total time of saponification across a wide range and again used HPLC to compare carotenoid concentrations among conditions. Astaxanthin and galloxanthin were the dominant carotenoids recovered in the quail retina, along with smaller amounts of five other carotenoids (lutein, zeaxanthin, 3'-epilutein, epsilon-carotene, and an unidentified carotenoid). Astaxanthin was sensitive to saponification conditions; recovery was poor with strong bases (0.2 and 0.5 M KOH) and best with weak bases (0.01 and 0.2 M KOH). In contrast, xanthophyll carotenoids (galloxanthin, zeaxanthin, lutein, 3'-epilutein, and the unknown) were best recovered with strong base after 6 hours of saponification at room temperature. The recovery of epsilon-carotene was not affected by saponification conditions. Separate chemical hydrolysis procedures--using a strong base to recover xanthophylls and a weak base to recover astaxanthin--should be used for maximizing recovery of quail retinal carotenoids. Because the dominant carotenoids in quail retina are absent in human retina, and because of their different packaging (e.g., esterified in oil droplets) and light-absorbance properties compared with xanthophylls in the human eye, use of the quail as a model organism for studying human retinal carotenoids should be approached with caution.

Ocular Pharmacokinetics of Naringenin Eye Drops Following Topical Administration to Rabbits

Science.gov (United States)

Lin, Junli; Sun, Jingjing; Wang, Yandong; Ma, Yan; Chen, Wenpei; Zhang, Ziyang; Gui, Gang

2015-01-01

Abstract Purpose: To investigate the ocular pharmacokinetics of 1% naringenin eye drops following topical administration to rabbits. Methods: One drop (50 μL) of 1% naringenin eye drops was instilled into both eyes of each rabbit. The animals were sacrificed at predetermined intervals after dosing, and ocular tissues and plasma were then collected. Concentrations of naringenin were analyzed using specific electrospray ionization liquid chromatography-tandem mass spectrometry method, which is proved to be sensitive, specific, precise, and suitable for determination of naringenin in ocular tissues and plasma of rabbits. Results: Ocular exposure to naringenin, based on AUC(0−t), was highest in cornea, followed by aqueous humor, retina, and vitreous body. The Cmax of naringenin in cornea, aqueous humor, vitreous body, and retina were 67945.30±4109.34 ng/g, 1325.69±239.34, 160.52±38.78 ng/mL, and 1927.08±660.77 ng/g at 0.083, 0.75, 0.083, and 0.083 h after topical administration, respectively. The half-lives for these tissues were 9.37, 0.65, 1.17, and 4.62 h, respectively. There was no significant difference between free naringenin and total naringenin in plasma based on Cmax and Tmax. Cmax of total naringenin in plasma at 0.083 h was 35.12±0.54 ng/mL. Conclusions: Measurable concentrations of naringenin were achieved in ocular tissues after topical application in rabbits. Topical instillation of naringenin may be an effective approach in the treatment of posterior section diseases. PMID:25229266

Does comorbid anxiety counteract emotion recognition deficits in conduct disorder?

Science.gov (United States)

Short, Roxanna M L; Sonuga-Barke, Edmund J S; Adams, Wendy J; Fairchild, Graeme

2016-08-01

Previous research has reported altered emotion recognition in both conduct disorder (CD) and anxiety disorders (ADs) - but these effects appear to be of different kinds. Adolescents with CD often show a generalised pattern of deficits, while those with ADs show hypersensitivity to specific negative emotions. Although these conditions often cooccur, little is known regarding emotion recognition performance in comorbid CD+ADs. Here, we test the hypothesis that in the comorbid case, anxiety-related emotion hypersensitivity counteracts the emotion recognition deficits typically observed in CD. We compared facial emotion recognition across four groups of adolescents aged 12-18 years: those with CD alone (n = 28), ADs alone (n = 23), cooccurring CD+ADs (n = 20) and typically developing controls (n = 28). The emotion recognition task we used systematically manipulated the emotional intensity of facial expressions as well as fixation location (eye, nose or mouth region). Conduct disorder was associated with a generalised impairment in emotion recognition; however, this may have been modulated by group differences in IQ. AD was associated with increased sensitivity to low-intensity happiness, disgust and sadness. In general, the comorbid CD+ADs group performed similarly to typically developing controls. Although CD alone was associated with emotion recognition impairments, ADs and comorbid CD+ADs were associated with normal or enhanced emotion recognition performance. The presence of comorbid ADs appeared to counteract the effects of CD, suggesting a potentially protective role, although future research should examine the contribution of IQ and gender to these effects. © 2016 Association for Child and Adolescent Mental Health.

Evaluación y conducta recomendada en presencia de precursores vítreorretinianos del desprendimiento de retina

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Ceija Molina Cisneros

Full Text Available Los cambios y las variaciones anatómicas vítreorretinianas predisponen al desprendimiento de retina regmatógeno, por lo que su conocimiento es de vital importancia para el tratamiento adecuado de los pacientes. Por ello se decidió realizar una revisión acerca de los elementos más importantes al respecto, con el objetivo de actualizar los conocimientos existentes sobre el tema. Estos precursores comprenden tres entidades que, por su fisiopatología, pueden estar presentes en la historia natural de esta afección: Desprendimiento de vítreo posterior, degeneraciones periféricas y desgarro de retina (sintomáticos y asintomáticos. Además, algunas situaciones de riesgo como la cirugía de catarata, la capsulotomía posterior con YAG-láser, los traumatismos y la miopía alta pueden favorecer también al desprendimiento de retina. Estos precursores, por lo general, se hacen más evidentes después de los 40 años, sin predilección por sexo o características raciales y están muy relacionadas con cambios vítreos o su licuefacción. El conocimiento básico y actualizado de estas entidades, así como de los factores de riesgo asociados al desprendimiento de retina es importante para el adecuado manejo y el control de las complicaciones. En la revisión se describen con claridad los pilares fundamentales para el diagnóstico y tratamiento de este tipo de situaciones clínicas.

Lateral feedback from monophasic horizontal cells to cones in carp retina. I. Experiments

NARCIS (Netherlands)

Kamermans, M.; van Dijk, B. W.; Spekreijse, H.; Zweypfenning, R. C.

1989-01-01

The spatial and color coding of the monophasic horizontal cells were studied in light- and dark-adapted retinae. Slit displacement experiments revealed differences in integration area for the different cone inputs of the monophasic horizontal cells. The integration area measured with a 670-nm

Macular pigment carotenoids in the retina and occipital cortex are related in humans

Science.gov (United States)

Objectives: Lutein and zeaxanthin are dietary carotenoids that preferentially accumulate in the macular region of the retina. Together with mesozeaxanthin, a conversion product of lutein in the macula, they form the macular pigment. Lutein is also the predominant carotenoid in human brain tissue and...

Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

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Protim Sarker

Full Text Available BACKGROUND: Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18 in the large intestinal epithelia. AIMS: To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB, a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. METHODS: The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR and release of the CAP-18 peptide/protein in stool (Western blot. PRINCIPAL FINDINGS: Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. CONCLUSION: Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from

Up-regulation of DRP-3 long isoform during the induction of neural progenitor cells by glutamate treatment in the ex vivo rat retina

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Tokuda, Kazuhiro, E-mail: r502um@yamaguchi-u.ac.jp [Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Kuramitsu, Yasuhiro; Byron, Baron; Kitagawa, Takao [Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Tokuda, Nobuko [Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube (Japan); Kobayashi, Daiki; Nagayama, Megumi; Araki, Norie [Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Sonoda, Koh-Hei [Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan); Nakamura, Kazuyuki [Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi (Japan)

2015-08-07

Glutamate has been shown to induce neural progenitor cells in the adult vertebrate retina. However, protein dynamics during progenitor cell induction by glutamate are not fully understood. To identify specific proteins involved in the process, we employed two-dimensional electrophoresis-based proteomics on glutamate untreated and treated retinal ex vivo sections. Rat retinal tissues were incubated with 1 mM glutamate for 1 h, followed by incubation in glutamate-free media for a total of 24 h. Consistent with prior reports, it was found that mitotic cells appeared in the outer nuclear layer without any histological damage. Immunohistological evaluations and immunoblotting confirmed the emergence of neuronal progenitor cells in the mature retina treated with glutamate. Proteomic analysis revealed the up-regulation of dihydropyrimidinase-related protein 3 (DRP-3), DRP-2 and stress-induced-phosphoprotein 1 (STIP1) during neural progenitor cell induction by glutamate. Moreover, mRNA expression of DRP-3, especially, its long isoform, robustly increased in the treated retina compared to that in the untreated retina. These results may indicate that glutamate induces neural progenitor cells in the mature rat retina by up-regulating the proteins which mediate cell mitosis and neurite growth. - Highlights: • Glutamate induced neuronal progenitor cells in the mature rat retina. • Proteomic analysis revealed the up-regulation of DRP-3, DRP-2 and STIP1. • mRNA expression of DRP-3, especially, its long isoform, robustly increased.

Foxg1 regulates retinal axon pathfinding by repressing an ipsilateral program in nasal retina and by causing optic chiasm cells to exert a net axonal growth-promoting activity.

Science.gov (United States)

Tian, Natasha M; Pratt, Thomas; Price, David J

2008-12-01

Mammalian binocular vision relies on the divergence of retinal ganglion cell axons at the optic chiasm, with strictly controlled numbers projecting contralaterally and ipsilaterally. In mouse, contralateral projections arise from the entire retina, whereas ipsilateral projections arise from ventrotemporal retina. We investigate how development of these patterns of projection is regulated by the contralateral determinant Foxg1, a forkhead box transcription factor expressed in nasal retina and at the chiasm. In nasal retina, loss of Foxg1 causes increased numbers of ipsilateral projections and ectopic expression of the ipsilateral determinants Zic2, Ephb1 and Foxd1, indicating that nasal retina is competent to express an ipsilateral program that is normally suppressed by Foxg1. Using co-cultures that combine Foxg1-expressing with Foxg1-null retinal explants and chiasm cells, we provide functional evidence that Foxg1 promotes contralateral projections through actions in nasal retina, and that in chiasm cells, Foxg1 is required for the generation of a hitherto unrecognized activity supporting RGC axon growth.

Simultaneous in vivo imaging of melanin and lipofuscin in the retina with photoacoustic ophthalmoscopy and autofluorescence imaging

Science.gov (United States)

Zhang, Xiangyang; Zhang, Hao F.; Puliafito, Carmen A.; Jiao, Shuliang

2011-08-01

We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective versus exacerbate) in the RPE in the aging process. We have successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina

DEFF Research Database (Denmark)

Campos, Elisa J.; Martins, João; Brudzewsky, Dan

2018-01-01

1 diabetes mellitus (DM) and sitagliptin, a DPP-IV inhibitor, on the NPY system in the retina using an animal model.  Methods: Type 1 DM was induced in male Wistar rats by an intraperitoneal injection of streptozotocin. Starting 2weeks after DM onset, animals were treated orally with sitagliptin (5...... of NPY to all receptors. Sitagliptin alone reduced retinal NPY mRNA levels. The effects of DM on the NPY system were not affected by sitagliptin.  Conclusion: DM modestly affects the NPY system in the retina and these effects are not prevented by sitagliptin treatment. These observations suggest that DPP...

Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

International Nuclear Information System (INIS)

Song, Yao; Baba, Tomohisa; Li, Ying-Yi; Furukawa, Kaoru; Tanabe, Yamato; Matsugo, Seiichi; Sasaki, Soichiro; Mukaida, Naofumi

2015-01-01

Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization

Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

Energy Technology Data Exchange (ETDEWEB)

Song, Yao; Baba, Tomohisa [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Li, Ying-Yi [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Furukawa, Kaoru; Tanabe, Yamato [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Matsugo, Seiichi [School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Sasaki, Soichiro [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Mukaida, Naofumi, E-mail: mukaida@staff.kanazawa-u.ac.jp [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan)

2015-03-06

Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization.

Automated pathologies detection in retina digital images based on complex continuous wavelet transform phase angles.

Science.gov (United States)

Lahmiri, Salim; Gargour, Christian S; Gabrea, Marcel

2014-10-01

An automated diagnosis system that uses complex continuous wavelet transform (CWT) to process retina digital images and support vector machines (SVMs) for classification purposes is presented. In particular, each retina image is transformed into two one-dimensional signals by concatenating image rows and columns separately. The mathematical norm of phase angles found in each one-dimensional signal at each level of CWT decomposition are relied on to characterise the texture of normal images against abnormal images affected by exudates, drusen and microaneurysms. The leave-one-out cross-validation method was adopted to conduct experiments and the results from the SVM show that the proposed approach gives better results than those obtained by other methods based on the correct classification rate, sensitivity and specificity.

Designing and testing scene enhancement algorithms for patients with retina degenerative disorders

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Downes Susan M

2010-06-01

Full Text Available Abstract Background Retina degenerative disorders represent the primary cause of blindness in UK and in the developed world. In particular, Age Related Macular Degeneration (AMD and Retina Pigmentosa (RP diseases are of interest to this study. We have therefore created new image processing algorithms for enhancing the visual scenes for them. Methods In this paper we present three novel image enhancement techniques aimed at enhancing the remaining visual information for patients suffering from retina dystrophies. Currently, the only effective way to test novel technology for visual enhancement is to undergo testing on large numbers of patients. To test our techniques, we have therefore built a retinal image processing model and compared the results to data from patient testing. In particular we focus on the ability of our image processing techniques to achieve improved face detection and enhanced edge perception. Results Results from our model are compared to actual data obtained from testing the performance of these algorithms on 27 patients with an average visual acuity of 0.63 and an average contrast sensitivity of 1.22. Results show that Tinted Reduced Outlined Nature (TRON and Edge Overlaying algorithms are most beneficial for dynamic scenes such as motion detection. Image Cartoonization was most beneficial for spatial feature detection such as face detection. Patient's stated that they would most like to see Cartoonized images for use in daily life. Conclusions Results obtained from our retinal model and from patients show that there is potential for these image processing techniques to improve visual function amongst the visually impaired community. In addition our methodology using face detection and efficiency of perceived edges in determining potential benefit derived from different image enhancement algorithms could also prove to be useful in quantitatively assessing algorithms in future studies.

Developmental and adult characterization of secretagogin expressing amacrine cells in zebrafish retina.

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Stefanie Dudczig

Full Text Available Calcium binding proteins show stereotypical expression patterns within diverse neuron types across the central nervous system. Here, we provide a characterization of developmental and adult secretagogin-immunolabelled neurons in the zebrafish retina with an emphasis on co-expression of multiple calcium binding proteins. Secretagogin is a recently identified and cloned member of the F-hand family of calcium binding proteins, which labels distinct neuron populations in the retinas of mammalian vertebrates. Both the adult distribution of secretagogin labeled retinal neurons as well as the developmental expression indicative of the stage of neurogenesis during which this calcium binding protein is expressed was quantified. Secretagogin expression was confined to an amacrine interneuron population in the inner nuclear layer, with monostratified neurites in the center of the inner plexiform layer and a relatively regular soma distribution (regularity index > 2.5 across central-peripheral areas. However, only a subpopulation (~60% co-labeled with gamma-aminobutyric acid as their neurotransmitter, suggesting that possibly two amacrine subtypes are secretagogin immunoreactive. Quantitative co-labeling analysis with other known amacrine subtype markers including the three main calcium binding proteins parvalbumin, calbindin and calretinin identifies secretagogin immunoreactive neurons as a distinct neuron population. The highest density of secretagogin cells of ~1800 cells / mm2 remained relatively evenly along the horizontal meridian, whilst the density dropped of to 125 cells / mm2 towards the dorsal and ventral periphery. Thus, secretagogin represents a new amacrine label within the zebrafish retina. The developmental expression suggests a possible role in late stage differentiation. This characterization forms the basis of functional studies assessing how the expression of distinct calcium binding proteins might be regulated to compensate for the loss

Developmentally Regulated Production of meso-Zeaxanthin in Chicken Retinal Pigment Epithelium/Choroid and Retina.

Science.gov (United States)

Gorusupudi, Aruna; Shyam, Rajalekshmy; Li, Binxing; Vachali, Preejith; Subhani, Yumna K; Nelson, Kelly; Bernstein, Paul S

2016-04-01

meso-Zeaxanthin is a carotenoid that is rarely encountered in nature outside of the vertebrate eye. It is not a constituent of a normal human diet, yet this carotenoid comprises one-third of the primate macular pigment. In the current study, we undertook a systematic approach to biochemically characterize the production of meso-zeaxanthin in the vertebrate eye. Fertilized White Leghorn chicken eggs were analyzed for the presence of carotenoids during development. Yolk, liver, brain, serum, retina, and RPE/choroid were isolated, and carotenoids were extracted. The samples were analyzed on C-30 or chiral HPLC columns to determine the carotenoid composition. Lutein and zeaxanthin were found in all studied nonocular tissues, but no meso-zeaxanthin was ever detected. Among the ocular tissues, the presence of meso-zeaxanthin was consistently observed starting at embryonic day 17 (E17) in the RPE/choroid, several days before its consistent detection in the retina. If RPE/choroid of an embryo was devoid of meso-zeaxanthin, the corresponding retina was always negative as well. This is the first report of developmentally regulated synthesis of meso-zeaxanthin in a vertebrate system. Our observations suggest that the RPE/choroid is the primary site of meso-zeaxanthin synthesis. Identification of meso-zeaxanthin isomerase enzyme in the developing chicken embryo will facilitate our ability to determine the biochemical mechanisms responsible for production of this unique carotenoid in other higher vertebrates, such as humans.

Histologic correlation of in vivo optical coherence tomography images of the human retina

NARCIS (Netherlands)

Chen, T.; Cense, B.; Miller, J.S.; Rubin, P. A. D.; Deschler, D. G.; Gragoudas, E. S.; de Boer, J.F.

2006-01-01

Purpose: To correlate in vivo human retina optical coherence tomography (OCT)3 images with histology. Design: Case series. Methods: Linear OCT3 scans through the macula and optic nerve were obtained in three eyes of three patients who then underwent exenteration surgery for orbital cancers. OCT3

Adaptation in Coding by Large Populations of Neurons in the Retina

Science.gov (United States)

Ioffe, Mark L.

A comprehensive theory of neural computation requires an understanding of the statistical properties of the neural population code. The focus of this work is the experimental study and theoretical analysis of the statistical properties of neural activity in the tiger salamander retina. This is an accessible yet complex system, for which we control the visual input and record from a substantial portion--greater than a half--of the ganglion cell population generating the spiking output. Our experiments probe adaptation of the retina to visual statistics: a central feature of sensory systems which have to adjust their limited dynamic range to a far larger space of possible inputs. In Chapter 1 we place our work in context with a brief overview of the relevant background. In Chapter 2 we describe the experimental methodology of recording from 100+ ganglion cells in the tiger salamander retina. In Chapter 3 we first present the measurements of adaptation of individual cells to changes in stimulation statistics and then investigate whether pairwise correlations in fluctuations of ganglion cell activity change across different stimulation conditions. We then transition to a study of the population-level probability distribution of the retinal response captured with maximum-entropy models. Convergence of the model inference is presented in Chapter 4. In Chapter 5 we first test the empirical presence of a phase transition in such models fitting the retinal response to different experimental conditions, and then proceed to develop other characterizations which are sensitive to complexity in the interaction matrix. This includes an analysis of the dynamics of sampling at finite temperature, which demonstrates a range of subtle attractor-like properties in the energy landscape. These are largely conserved when ambient illumination is varied 1000-fold, a result not necessarily apparent from the measured low-order statistics of the distribution. Our results form a consistent

Regulating Rumination by Anger: Evidence for the Mutual Promotion and Counteraction (MPMC Theory of Emotionality

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Jun Zhan

2017-12-01

Full Text Available Unlike the strategy of cognitive regulation that relies heavily on the top-down control function of the prefrontal cortex (PFC, which was recently found may be critically impaired in stressful situations, traditional Chinese philosophy and medicine views different types of emotionality as having mutual promotion and counteraction (MPMC relationships, implying a novel approach that requires less cognition to emotional regulation. Actually, our previous studies have indicated that anger responses could be successfully regulated via the induction of sadness, and this efficiency could not be influenced by stress, thus providing evidences for the hypothesis of “sadness counteracts anger” (SCA proposed by the MPMC theory of emotionality (Zhan et al., 2015, 2017. In this study, we experimentally examined the MPMC hypothesis that “anger counteracts rumination” (ACR which postulates that rumination may be alleviated by the anger emotion. In Study 1, all participants were initially caused state rumination and then induced anger, joy or neutral mood, the results showed that the rumination-related affect was alleviated after anger induction relative to that after joy or neutral mood induction. In Study 2, female participants with high trait rumination were recruited and divided into two groups for exposure to an anger or neutral emotion intervention, the result indicated that the anger intervention group exhibited a greater decline in trait rumination than the neutral emotion intervention group. These findings provided preliminary evidence supporting the hypothesis of ACR, which suggested a new strategy that employs less cognitive resources to regulating state and trait rumination by inducing anger.

Regulating Rumination by Anger: Evidence for the Mutual Promotion and Counteraction (MPMC) Theory of Emotionality

Science.gov (United States)

Zhan, Jun; Tang, Fan; He, Mei; Fan, Jin; Xiao, Jing; Liu, Chang; Luo, Jing

2017-01-01

Unlike the strategy of cognitive regulation that relies heavily on the top-down control function of the prefrontal cortex (PFC), which was recently found may be critically impaired in stressful situations, traditional Chinese philosophy and medicine views different types of emotionality as having mutual promotion and counteraction (MPMC) relationships, implying a novel approach that requires less cognition to emotional regulation. Actually, our previous studies have indicated that anger responses could be successfully regulated via the induction of sadness, and this efficiency could not be influenced by stress, thus providing evidences for the hypothesis of “sadness counteracts anger” (SCA) proposed by the MPMC theory of emotionality (Zhan et al., 2015, 2017). In this study, we experimentally examined the MPMC hypothesis that “anger counteracts rumination” (ACR) which postulates that rumination may be alleviated by the anger emotion. In Study 1, all participants were initially caused state rumination and then induced anger, joy or neutral mood, the results showed that the rumination-related affect was alleviated after anger induction relative to that after joy or neutral mood induction. In Study 2, female participants with high trait rumination were recruited and divided into two groups for exposure to an anger or neutral emotion intervention, the result indicated that the anger intervention group exhibited a greater decline in trait rumination than the neutral emotion intervention group. These findings provided preliminary evidence supporting the hypothesis of ACR, which suggested a new strategy that employs less cognitive resources to regulating state and trait rumination by inducing anger. PMID:29249998

Distribution and protective function of pituitary adenylate cyclase-activating polypeptide (PACAP in the retina

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Tomoya eNakamachi

2012-11-01

Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP, which is found in 27- or 38-amino acid forms, belongs to the VIP/glucagon/secretin family. PACAP and its three receptor subtypes are expressed in neural tissues, with PACAP known to exert a protective effect against several types of neural damage. The retina is considered to be part of the central nervous system, and retinopathy is a common cause of profound and intractable loss of vision. This review will examine the expression and morphological distribution of PACAP and its receptors in the retina, and will summarize the current state of knowledge regarding the protective effect of PACAP against different kinds of retinal damage, such as that identified in association with diabetes, ultraviolet light, hypoxia, optic nerve transection, and toxins. This article will also address PACAP-mediated protective pathways involving retinal glial cells.

The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats.

Science.gov (United States)

Pitsikas, Nikolaos; Gravanis, Achille

2017-04-01

Experimental evidence indicates that the neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) are involved in cognition. BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Maldistribution in air-water heat pump evaporators. Part 2: Economic analysis of counteracting technologies

DEFF Research Database (Denmark)

Mader, Gunda; Palm, Björn; Elmegaard, Brian

2015-01-01

maldistribution,high electricity prices, and colder climate. Investment in the individual superheat controltechnology, however, can be quickly amortized in many scenarios. For the warmer climatezone with a small number of operating hours counteracting of maldistribution does notpay off under the used economic...... assumptions.© 2014 Elsevier Ltd and IIR. All rights reserved....

Instant website optimization for retina displays how-to

CERN Document Server

Larson, Kyle J

2013-01-01

Written in an accessible and practical manner which quickly imparts the knowledge you want to know. As a How-to book it will use applied examples and teach you to optimize websites for retina displays. This book is for web designers and developers who are familiar with HTML, CSS, and editing graphics who would like to improve their existing website or their next web project with high-resolution images. You'll need to have a high-definition device to be able to test the examples in this book and a server to upload your code to if you're not developing it on that device.

Counteracting media’s thin body ideal in adolescent girls: informing is more effective than warning.

NARCIS (Netherlands)

Veldhuis, J.; Konijn, E.A.; Seidell, J.C.

2014-01-01

The present study investigated whether information or warnings about depictions of the thin-body ideal in mass media are effective in counteracting media-induced negative body perceptions of adolescent girls. Based on counter-advertising and reactance theories, our hypotheses were tested in a 3

Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE)

Science.gov (United States)

Sharon, Dror; Blackshaw, Seth; Cepko, Constance L.; Dryja, Thaddeus P.

2002-01-01

We used the serial analysis of gene expression (SAGE) technique to catalogue and measure the relative levels of expression of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium (RPE) from one or both of two humans, aged 88 and 44 years. The cone photoreceptor contribution to all transcription in the retina was found to be similar in the macula versus the retinal periphery, whereas the rod contribution was greater in the periphery versus the macula. Genes encoding structural proteins for axons were found to be expressed at higher levels in the macula versus the retinal periphery, probably reflecting the large proportion of ganglion cells in the central retina. In comparison with the younger eye, the peripheral retina of the older eye had a substantially higher proportion of mRNAs from genes encoding proteins involved in iron metabolism or protection against oxidative damage and a substantially lower proportion of mRNAs from genes encoding proteins involved in rod phototransduction. These differences may reflect the difference in age between the two donors or merely interindividual variation. The RPE library had numerous previously unencountered tags, suggesting that this cell type has a large, idiosyncratic repertoire of expressed genes. Comparison of these libraries with 100 reported nonocular SAGE libraries revealed 89 retina-specific or enriched genes expressed at substantial levels, of which 14 are known to cause a retinal disease and 53 are RPE-specific genes. We expect that these libraries will serve as a resource for understanding the relative expression levels of genes in the retina and the RPE and for identifying additional disease genes. PMID:11756676

PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina

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Jack W Hickmott

2016-01-01

Full Text Available Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6 gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina.

Science.gov (United States)

Hickmott, Jack W; Chen, Chih-Yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

2016-01-01

Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina.

Science.gov (United States)

Miyawaki, Takaya; Uemura, Akiyoshi; Dezawa, Mari; Yu, Ruth T; Ide, Chizuka; Nishikawa, Shinichi; Honda, Yoshihito; Tanabe, Yasuto; Tanabe, Teruyo

2004-09-15

Tlx belongs to a class of orphan nuclear receptors that underlies many aspects of neural development in the CNS. However, the fundamental roles played by Tlx in the control of eye developmental programs remain elusive. By using Tlx knock-out (KO) mice, we show here that Tlx is expressed by retinal progenitor cells in the neuroblastic layer during the period of retinal layer formation, and it is critical for controlling the generation of appropriate numbers of retinal progenies through the activities of cell cycle-related molecules, cyclin D1 and p27Kip1. Tlx expression is restricted to Müller cells in the mature retina and appears to control their proper development. Furthermore, we show that Tlx is expressed by immature astrocytes that migrate from the optic nerve onto the inner surface of the retina and is required for their generation and maturation, as assessed by honeycomb network formation and expression of R-cadherin, a critical component for vasculogenesis. The impaired astrocyte network formation on the inner retinal surface is accompanied by the loss of vasculogenesis in Tlx KO retinas. Our studies thus indicate that Tlx underlies a fundamental developmental program of retinal organization and controls the generation of the proper numbers of retinal progenies and development of glial cells during the protracted period of retinogenesis.

Circadian expression of clock genes and clock-controlled genes in the rat retina

NARCIS (Netherlands)

Kamphuis, Willem; Cailotto, Cathy; Dijk, Frederike; Bergen, Arthur; Buijs, Ruud M.

2005-01-01

The circadian expression patterns of genes encoding for proteins that make up the core of the circadian clock were measured in rat retina using real-time quantitative PCR (qPCR). Transcript levels of several genes previously used for normalization of qPCR assays were determined and the effect of

Current means for raising efficiency of counteraction to counterfeit goods trafficking

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Dronova O.B.

2014-12-01

Full Text Available The urgency of counteraction to counterfeit goods trafficking is shown. Annual loss due to counterfeit goods producing and trafficking reaches several billion dollars. There remains a danger of buying low-quality and counterfeit goods despite implementing new producing techniques and protective elements. Measures, taken by law enforcement agencies, state authorities and public human rights organizations have not led to systematic suppression of producing and trafficking of such goods. Creation of new information and reference resource, containing information blocks of protective symbols on goods and packages and illustrated materials comprising patterns of discovered counterfeit goods, can assist to increase public awareness and to give necessary information to law enforcement agencies. Organizations, realizing state and social protection of consumers and entrepreneurs, along with producers, rightholders’ representatives and law enforcement bodies can accept the responsibility of creating and functioning this information and reference system in the Internet. Such level of cooperation of all interested organizations will allow to raise efficiency of measures for counteraction to trafficking goods with violated consumer properties. The author proves the necessity to organize functioning of information and reference resource for a wide range of users. Operation of such resource should comply with main principles of generating any information resource, notably full scale, authenticity and relevance of information. The author proposes the algorithm of creating such system which provides cooperation of law enforcement agencies, producers and consumers for the purpose of preventing counterfeit goods trafficking and investigating committed crimes.

P3-7: On Prototyping a Visual Prosthesis System with Artificial Retina and Optic Nerve Based on Arrayed Microfibers

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Jian Hong Chen

2012-10-01

Full Text Available The traditional visual prosthesis system combines both a camera and a microelectrode array implanted on the visual neural network including retina, optic nerve, and visual cortex. Here, we introduce a new visual prosthesis system in which an artificial retina and optic nerve are demonstrated. The prototype of optic nerve for image transmission is comprised of arrayed PMMA microfibers with both ends connected with two planes, one functioned as retina for light reception and another attached to visual cortex. The microfibers are drawn from the thin film prepared by PMMA/chlorobenzene solution. Each micro fiber serves as an optical waveguide for the delivery of a single image pixel. It is demonstrated that with proper imaging optics, arrayed micro fibers could be lit as discrete light spots in accordance with the input image. Each micro fiber is expected to function as a stimulation unit for optical neural modulation in a visual prosthesis system.

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

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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.

Direct localised measurement of electrical resistivity profile in rat and embryonic chick retinas using a microprobe

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Harald van Lintel

2010-01-01

Full Text Available We report an alternative technique to perform a direct and local measurement of electrical resistivities in a layered retinal tissue. Information on resistivity changes along the depth in a retina is important for modelling retinal stimulation by retinal prostheses. Existing techniques for resistivity-depth profiling have the drawbacks of a complicated experimental setup, a less localised resistivity probing and/or lower stability for measurements. We employed a flexible microprobe to measure local resistivity with bipolar impedance spectroscopy at various depths in isolated rat and chick embryo retinas for the first time. Small electrode spacing permitted high resolution measurements and the probe flexibility contributed to stable resistivity profiling. The resistivity was directly calculated based on the resistive part of the impedance measured with the Peak Resistance Frequency (PRF methodology. The resistivity-depth profiles for both rat and chick embryo models are in accordance with previous mammalian and avian studies in literature. We demonstrate that the measured resistivity at each depth has its own PRF signature. Resistivity profiles obtained with our setup provide the basis for the construction of an electric model of the retina. This model can be used to predict variations in parameters related to retinal stimulation and especially in the design and optimisation of efficient retinal implants.

Quantum system under the actions of two counteracting baths: A model for the attenuation-amplification interplay

International Nuclear Information System (INIS)

Lorenzen, F.; Moussa, M. H. Y.; Ponte, M. A. de; Almeida, N. G. de

2009-01-01

We analyze the dynamical behavior of a quantum system under the actions of two counteracting baths: the inevitable energy draining reservoir and, in opposition, exciting the system, an engineered Glauber's amplifier. We follow the system dynamics towards equilibrium to map its distinctive behavior arising from the interplay of attenuation and amplification. Such a mapping, with the corresponding parameter regimes, is achieved by calculating the evolution of both the excitation and the Glauber-Sudarshan P function. Techniques to compute the decoherence and the fidelity of quantum states under the action of both counteracting baths, based on the Wigner function rather than the density matrix, are also presented. They enable us to analyze the similarity of the evolved state vector of the system with respect to the original one, for all regimes of parameters. Applications of this attenuation-amplification interplay are discussed.

Retinal pathology is associated with increased blood-retina barrier permeability in a diabetic and hypercholesterolaemic pig model: Beneficial effects of the LpPLA2 inhibitor Darapladib.

Science.gov (United States)

Acharya, Nimish K; Qi, Xin; Goldwaser, Eric L; Godsey, George A; Wu, Hao; Kosciuk, Mary C; Freeman, Theresa A; Macphee, Colin H; Wilensky, Robert L; Venkataraman, Venkat; Nagele, Robert G

2017-05-01

Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta 1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib. These findings suggest that chronic diabetes mellitus and hypercholesterolaemia induces increased blood-retina barrier permeability that may be linked to altered expression of blood-retina barrier-associated tight junction proteins, claudin and occludin, leading to structural changes in the retina consistent with diabetic retinopathy. Additionally, results suggest that drugs with vascular anti-inflammatory properties, such as Darapladib, may have beneficial effects on eye diseases strongly linked to vascular abnormalities such as diabetic retinopathy and age-related macular degeneration.

Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia.

Science.gov (United States)

Xue, Kanmin; Oldani, Marta; Jolly, Jasleen K; Edwards, Thomas L; Groppe, Markus; Downes, Susan M; MacLaren, Robert E

2016-07-01

To evaluate the relationships between RPE, photoreceptor, and choroidal degeneration in choroideremia. Enhanced-depth imaging optical coherence tomography (EDI-OCT), scanning laser ophthalmoscopy (SLO), and autofluorescence (AF) were performed on 39 patients (78 eyes) with choroideremia. The edges of surviving outer retina on OCT and residual AF were aligned. The distribution of outer retinal tubulations was mapped over a range of ages (16-71 years), and comparison made between pre- and postsubretinal gene therapy. Subfoveal choroidal thickness (SFCT) was compared between 23 choroideremia patients (42 eyes) and 20 age- and refraction-matched male controls (40 eyes). The edges of RPE AF aligned with a reduction in outer nuclear layer thickness (Spearman's rho = 0.9992). Correlation was also found between the quality of AF and integrity of ellipsoid zone within islands of surviving retina. Tubulations existed in 71 of 78 (91%) eyes with choroideremia and remained stable following gene therapy. Subfoveal choroidal thickness was reduced at baseline in choroideremia (179.7 ± 17.2 μm) compared with controls (302.0 ± 4.8 μm; P retina and hence being potentially light responsive (ClinicalTrials.gov, NCT01461213).

THE EYE — MIRROR OF CARDIOVASCULAR DISORDER. RELATIONSHIP OF THE RETINA FUNCTIONAL STATE AND THE HYPERTENSION SEVERITY

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V. S. Zadionchenko

2011-01-01

Full Text Available Aim. To study the retina state by functional methods in patients with arterial hypertension (HT of various degrees. Material and methods. Patients with uncomplicated HT of 1-3 degrees (n=81 and healthy subjects (n=20 of control group were examined. Routine (direct ophthalmoscopy and functional (evaluation of contrast and color sensitivity of the retina, electroretinography methods were used. Results. Functional retinal changes (reduction in color and contrast sensitivity progressed with increasing HT degree. These changes were located in the area of central retinal artery (paramacular area and area of choroidal blood flow (macular region. Retinal bioelectrical activity disturbance was also found by the electroretinography. Conclusion. The identified functional disorders suggest the retina involvement in the pathological process even in the early HT and may be associated with its severity. It confirms a relationship of HT with disorders of eye as a target organ in HT. Published data and results of our studies can refute the point of view about impossibility of changes assessment on the eye fundus in patients with uncomplicated HT, and indicates that it was premature exclusion of the eye from the list of target organs in HT.

Success Counteracting Tobacco Company Interference in Thailand: An Example of FCTC Implementation for Low- and Middle-income Countries

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Stephen L. Hamann

2012-03-01

Full Text Available Transnational tobacco companies (TTCs interfere regularly in policymaking in low- and middle-income countries (LMICs. The WHO Framework Convention for Tobacco Control provides mechanisms and guidance for dealing with TTC interference, but many countries still face ‘how to’ challenges of implementation. For more than two decades, Thailand’s public health community has been developing a system for identifying and counteracting strategies TTCs use to derail, delay and undermine tobacco control policymaking. Consequently, Thailand has already implemented most of the FCTC guidelines for counteracting TTC interference. In this study, our aims are to describe strategies TTCs have used in Thailand to interfere in policymaking, and to examine how the public health community in Thailand has counteracted TTC interference. We analyzed information reported by three groups with a stake in tobacco control policies: Thai tobacco control advocates, TTCs, and international tobacco control experts. To identify TTC viewpoints and strategies, we also extracted information from internal tobacco industry documents. We synthesized these data and identified six core strategies TTCs use to interfere in tobacco control policymaking: (1 doing business with ‘two faces’, (2 seeking to influence people in high places, (3 ‘buying’ advocates in grassroots organizations, (4 putting up a deceptive front, (5 intimidation, and (6 undermining controls on tobacco advertising, promotion and sponsorship. We present three case examples showing where TTCs have employed multiple interference strategies simultaneously, and showing how Thai tobacco control advocates have successfully counteracted those strategies by: (1 conducting vigilant surveillance, (2 excluding tobacco companies from policymaking, (3 restricting tobacco company sales, (4 sustaining pressure, and (5 dedicating resources to the effective enforcement of regulations. Policy implications from this study are

Strategies used to counteract bullying in schools : a comparative study / Wendy Batterbee

OpenAIRE

Batterbee, Wendy Ann

2007-01-01

This is an in-depth comparative study of the strategies used to counteract bullying at schools. It provides an international perspective on such strategies: Studies in South African schools are used to provide an African perspective: Australian research is used to provide an Oceanian perspective: Japanese research to provide an Asian perspective; and research conducted in England is used to provide an European perspective on bullying at schools. The extent and nature of bullying in schools...

Ocular distribution of antioxidant enzyme paraoxonase & its alteration in cataractous lens & diabetic retina

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Subramaniam Rajesh Bharathidevi

2017-01-01

Interpretation & conclusions: Distribution of PON enzyme and its activity in ocular tissues is reported here. The study revealed maximal PON activity in lens and retina, which are prone to higher oxidative stress. Differential activities of PON were observed in the lens and retinal tissues from cataractous and diabetic patients, respectively.

Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s.

Science.gov (United States)

Gu, Qinyong; Zhang, Zeli; Cano Ortiz, Lucía; Franco, Ana Cláudia; Häussinger, Dieter; Münk, Carsten

2016-12-01

Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain. Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z

Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

Science.gov (United States)

Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

2013-10-29

In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

Proteomic profiling of early degenerative retina of RCS rats.

Science.gov (United States)

Zhu, Zhi-Hong; Fu, Yan; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin

2017-01-01

To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs). Bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student's t -test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

Proteomic profiling of early degenerative retina of RCS rats

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Zhi-Hong Zhu

2017-06-01

Full Text Available AIM: To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP. METHODS: Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs. Bioinformatics analyses, including Gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. RESULTS: In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student’s t-test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. CONCLUSION: We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

A Case for Relational Leadership and an Ethics of Care for Counteracting Bullying at Schools

Science.gov (United States)

Smit, Brigitte; Scherman, Vanessa

2016-01-01

This paper attends to a theoretical exposition of relational leadership and ethics care as complementary approaches to educational leadership in counteracting bullying at schools. Schools constitute complex systems of activities, processes and dynamics. More specifically, a social system in schools is a web of interactions between the various…

Ethambutol induces impaired autophagic flux and apoptosis in the rat retina

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Shun-Ping Huang

2015-08-01

Full Text Available Ethambutol (EMB, an effective first-line antituberculosis agent, can cause serious visual impairment or irreversible vision loss in a significant number of patients. However, the mechanism underlying this ocular cytotoxicity remains to be elucidated. In this study, we found that there were statistically significant dose- and time-dependent increases in the number of cytoplasmic vacuoles and the level of cell death in EMB-treated RGC-5 cells (retinal ganglion cells. The protein kinase C (PKCδ inhibitor rottlerin markedly reduced the EMB-induced activation of caspase-3 and the subsequent apoptosis of RGC-5 cells. Western blot analysis revealed that the expression levels of class III PI3K, Beclin-1, p62 and LC3-II were upregulated, and LC3 immunostaining results showed activation of the early phase and inhibition of the late stage of autophagy in retinas of the EMB-intraperitoneal (IP-injected rat model. We further demonstrated that exposure to EMB induces autophagosome accumulation, which results from the impaired autophagic flux that is mediated by a PKCδ-dependent pathway, inhibits the PI3K/Akt/mTOR signaling pathway and leads to apoptotic death in retina neuronal cells. These results indicate that autophagy dysregulation in retinal neuronal cells might play a substantial role in EMB-induced optic neuroretinopathy.

Efferent influences on the bioelectrical activity of the retina in primates.

Science.gov (United States)

Ortiz, Gonzalo; Odom, J Vernon; Passaglia, Christopher L; Tzekov, Radouil T

2017-02-01

The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established. Such a feedback pathway could have important functional, clinical, and experimental significance to the field of vision science and ophthalmology. Following a comprehensive literature review (PubMed and Google Scholar, until July 2016), we present evidence regarding a system that can influence the bioelectrical activity of the retina in primates. Anatomical and physiological evidences are presented separately. Improvements in histological staining and the advent of retrograde nerve fiber tracers have allowed for more confidence in the identification of efferent optic nerve fibers, including back to their point of origin. Even with the accumulation of more modern anatomical and physiological evidence, some limitations and uncertainties about crucial details regarding the origins and role of a top-down, efferent system still exist. However, the summary of the evidence from earlier and more modern studies makes a compelling case in support of such a system in humans and non-human primates.

A Novel Nanoparticle Mediated Selective Inner Retinal Photocoagulation for Diseases of the Inner Retina.

Science.gov (United States)

Singh, Rupesh; Rajaraman, Srinivas; Balasubramanian, Madhusudhanan

2017-10-01

A novel nanoparticle mediated methodology for laser photocoagulation of the inner retina to achieve tissue selective treatment is presented. Transport of 527, 577, and 810 nm laser, heat deposition, and eventual thermal damage in vitreous, retina, RPE, choroid, and sclera were modeled using Bouguer-Beer-Lambert law of absorption and solved numerically using the finite volume method. Nanoparticles were designed using Mie theory of scattering. Performance of the new photocoagulation strategy using gold nanospheres and gold-silica nanoshells was compared with that of conventional methods without nanoparticles. For experimental validation, vitreous cavity of ex vivo porcine eyes was infused with gold nanospheres. After ~6 h of nanoparticle diffusion, the porcine retina was irradiated with a green laser and imaged simultaneously using a spectral domain optical coherence tomography (Spectralis SD-OCT, Heidelberg Engineering). Our computational model predicted a significant spatial shift in the peak temperature from RPE to the inner retinal region when infused with nanoparticles. Arrhenius thermal damage in the mid-retinal location was achieved in ~14 ms for 527 nm laser thereby reducing the irradiation duration by ~30 ms compared with the treatment without nanoparticles. In ex vivo porcine eyes infused with gold nanospheres, SD-OCT retinal images revealed a lower thermal damage and expansion at RPE due to laser photocoagulation. Nanoparticle infused laser photocoagulation strategy provided a selective inner retinal thermal damage with significant decrease in laser power and laser exposure time. The proposed treatment strategy shows possibilities for an efficient and highly selective inner retinal laser treatment.

The retina of Spalax ehrenbergi: novel histologic features supportive of a modified photosensory role.

NARCIS (Netherlands)

Cernuda-Cernuda, R.; Grip, W.J. de; Cooper, H.M.; Nevo, E.; Garcia-Fernandez, J.M.

2002-01-01

PURPOSE: The retina of the blind mole rat Spalax ehrenbergi was compared with other vertebrate photosensitive organs in an attempt to correlate its histologic organization with a presumptive nonvisual photoreceptor role. METHODS: The eyes of eight adult animals were analyzed by light and electron

Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

NARCIS (Netherlands)

Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

2012-01-01

In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance

Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation

OpenAIRE

Hanken, Katrin; Bosse, Mona; M?hrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

2016-01-01

BACKGROUND: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. OBJECTIVES: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. METHODS: In study I, a randomized double-blind placebo-controll...

Qualitative and quantitative autoradiographic investigations on DNA-repair in the pars optica retinae of the rabbit

International Nuclear Information System (INIS)

Kellner, G.; Reindl, E.; Pichler, L.; Hofer, H.

1974-01-01

In vitro and in vivo investigations into the incorporation of 3 H-thymidine into the nuclei of pars optica retinae of rabbits after β-irradiation with 60 krad were performed. The results of the in vitro and in vivo experiments are comparable with the in vitro data showing smaller statistical deviations. The rate comparable with the in vitro data showing smaller statistical deviations. The rate of incorporation of 3 H-thymidine into the nuclei of Ggl. opticum and Ggl. retinae is about the same, but it is significantly lower in the nuclei of photoreceptor cells by one order of magnitude. The in vitro experiment demonstrates that ganglion cells are capable of DNA repair even after circulation has been stopped for 15 or more minutes. (author)

Optimal wavelet transform for the detection of microaneurysms in retina photographs

OpenAIRE

Quellec, Gwénolé; Lamard, Mathieu; Josselin, Pierre Marie; Cazuguel, Guy; Cochener, Béatrice; Roux, Christian

2008-01-01

11 pages; International audience; In this paper, we propose an automatic method to detect microaneurysms in retina photographs. Microaneurysms are the most frequent and usually the first lesions to appear as a consequence of diabetic retinopathy. So, their detection is necessary for both screening the pathology and follow up (progression measurement). Automating this task, which is currently performed manually, would bring more objectivity and reproducibility. We propose to detect them by loc...

Evidence for RPE65-independent vision in the cone-dominated zebrafish retina.

Science.gov (United States)

Schonthaler, Helia B; Lampert, Johanna M; Isken, Andrea; Rinner, Oliver; Mader, Andreas; Gesemann, Matthias; Oberhauser, Vitus; Golczak, Marcin; Biehlmaier, Oliver; Palczewski, Krzysztof; Neuhauss, Stephan C F; von Lintig, Johannes

2007-10-01

An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all-trans to 11-cis-retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision.

The protective effects of the proteasome inhibitor bortezomib (velcade on ischemia-reperfusion injury in the rat retina.

Directory of Open Access Journals (Sweden)

Fang-Ting Chen

Full Text Available PURPOSE: To evaluate the protective effects of bortezomib (Velcade on ischemia-reperfusion (IR injury in the rat retina. METHODS: The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg, or high-dose bortezomib (0.2 mg/kg before the induction of IR injury. Electroretinography (ERG was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α, anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin, and pro-apoptotic proteins (p53, bax were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein, NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells. RESULTS: ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group. CONCLUSIONS: Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

Differences in Pre and Post Vascular Patterning of Retinas from ISS Crew Members and HDT Subjects by VESGEN Analysis

Science.gov (United States)

Murray, M. C.; Vizzeri, G.; Taibbi, G.; Mason, S. S.; Young, M. H.; Zanello, S. B.; Parsons-Wingerter, P. A.

2018-01-01

Accelerated research by NASA [1] has investigated the significant risks for visual and ocular impairments Spaceflight Associated Neuro-Ocular Syndrome /Visual Impairment/Intracranial Pressure (SANS/VIIP) incurred by microgravity spaceflight, especially long-duration missions. Our study investigates the role of blood vessels in the incidence and etiology of SANS/VIIP within the retinas of Astronaut crewmembers pre-and post-flight to the International Space Station (ISS) by NASA's VESsel GENeration Analysis (VESGEN). The response of retinal vessels in crewmembers to microgravity was compared to that of retinal vessels to Head-Down Tilt (HDT) in subjects undergoing 70-Day Bed Rest. The study tests the proposed hypothesis that cephalad fluid shifts missions, resulting in ocular and visual impairments, are necessarily mediated in part by retinal blood vessels, and are therefore accompanied by significant remodeling of retinal vasculature.Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30° infrared (IR) Heidelberg Spectralis® images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues [2]. The weighted, multi-parametric VESGEN analysis generates maps of branching arterial and venous trees and quantification by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations by vascular physiological branching rules [2,3]. The retrospective study approved by NASA’s Institutional Review Board included six HDT subjects (NASA Flight Analogs Research Unit [FARU] Campaign 11; for example, [4]) and eight ISS crewmembers monitored by routine occupational surveillance who provided their study consents to NASA’s Lifetime

Tratamento da necrose aguda de retina: revisão sistemática Treatment of acute retinal necrosis: systematic review

Directory of Open Access Journals (Sweden)

Moysés Eduardo Zajdenweber

2005-08-01

Full Text Available OBJETIVO: O objetivo deste estudo foi pela realização de revisão sistemática, determinar o melhor tratamento para a necrose aguda de retina. MÉTODOS: Seguindo a orientação metodológica da Colaboração Cochrane e de seu subgrupo editorial "Eye and Vision Group", o autor, por meio de mecanismos de busca, selecionou trabalhos sobre o tratamento da necrose aguda de retina. RESULTADO: Foram selecionadas 146 referências bibliográficas, sendo considerados como relevantes 13 estudos. Destes estudos 2 foram considerados como preenchendo os critérios de inclusão. O primeiro estudo aponta a possibilidade de o tratamento para necrose aguda de retina, com aciclovir endovenoso associado a corticóide sistêmico, proteger o olho contralateral de acometimento. Foram estudados 54 pacientes, 31 tratados e 23 não tratados, sendo observada incidência de doença no olho contralateral de 12,9% no grupo tratado e de 69,5% no grupo não tratado. O segundo estudo incluído mostra 19 olhos acometidos com necrose aguda de retina, sendo que 12 destes olhos foram submetidos à fotocoagulação com laser de argônio, com o objetivo de prevenir o descolamento de retina. Dos 12 olhos, 2 desenvolveram descolamento de retina (16,6% ao passo que, no grupo não tratado, composto por 7 olhos, 4 desenvolveram descolamento de retina (57,1%. CONCLUSÃO: O autor conclui que os dois tipos de intervenção propostos se mostraram eficazes, porém, como os estudos são metodologicamente fracos, torna-se necessária a realização de estudos clínicos randomizados para que se possa estabelecer o melhor tratamento para a necrose aguda de retina.PURPOSE: The purpose of this study was to identify, according to an sistematic review, the best treatment for acute retinal necrosis. METHODS: Following the methodologic guidance of the Cochrane Collaboration and its editorial subgroup "Eye and Vision Group", using search strategy for study identification, articles about the treatment

Spectral sensitivity of the feedback signal from horizontal cells to cones in goldfish retina

NARCIS (Netherlands)

Kraaij, D. A.; Kamermans, M.; Spekreijse, H.

1998-01-01

The spectral sensitivity of cones in isolated goldfish retina was determined with whole-cell recording techniques. Three spectral classes of cones were found with maximal sensitivities around 620 nm, 540 nm, and 460 nm. UV-cones were not found because our stimulator did not allow effective

Host cell reactivation by fibroblasts from patients with pigmentary degeneration of the retina

International Nuclear Information System (INIS)

Lytle, C.D.; Tarone, R.E.; Barrett, S.F.; Robbins, J.H.; Wirtschafter, J.D.; Dupuy, J.-M.

1983-01-01

Cockayne syndrome (CS) is an autosomal recessive disease characterized by numerous clinical abnormalities including acute sun sensitivity and primary pigmentary degeneration of the retina. Cultured fibroblasts from CS patients are hypersensitive to ultraviolet radiation. Host cell reactivation of irradiated virus was studied in CS and in other diseases with retinal degeneration to evaluate repair. The survival of UV-irradiated Herpes simplex virus type 1 was determined in fibroblast lines from four normal donors, two patients with CS, one with both xeroderma pigmentosum (XP) and CS, and from several other patients with (Usher syndrome, olivopontocerebellar atrophy, retinitis pigmentosa) and without (XP, ataxia telangiectasia) primary pigmentary degeneration of the retina. The viral survival curves in all cell lines showed two components: a very sensitive initial component followed by an exponential, less sensitive component. The exponential component had greater sensitivity than normal in the case of the CS patients, the patient with both XP and CS, and the XP patient. It was proposed that patients with CS have defective repair of DNA which may be the cause of their retinal degeneration. (author)

Host cell reactivation by fibroblasts from patients with pigmentary degeneration of the retina

Energy Technology Data Exchange (ETDEWEB)

Lytle, C.D. (Food and Drug Administration, Rockville, MD (USA)); Tarone, R.E.; Barrett, S.F.; Robbins, J.H. (National Cancer Inst., Bethesda, MD (USA)); Wirtschafter, J.D. (Minnesota Univ., Minneapolis (USA). Hospitals); Dupuy, J.M. (Quebec Univ., Laval-des-Rapides (Canada). Inst. Armand-Frappier)

1983-05-01

Cockayne syndrome (CS) is an autosomal recessive disease characterized by numerous clinical abnormalities including acute sun sensitivity and primary pigmentary degeneration of the retina. Cultured fibroblasts from CS patients are hypersensitive to ultraviolet radiation. Host cell reactivation of irradiated virus was studied in CS and in other diseases with retinal degeneration to evaluate repair. The survival of UV-irradiated Herpes simplex virus type 1 was determined in fibroblast lines from four normal donors, two patients with CS, one with both xeroderma pigmentosum (XP) and CS, and from several other patients with (Usher syndrome, olivopontocerebellar atrophy, retinitis pigmentosa) and without (XP, ataxia telangiectasia) primary pigmentary degeneration of the retina. The viral survival curves in all cell lines showed two components: a very sensitive initial component followed by an exponential, less sensitive component. The exponential component had greater sensitivity than normal in the case of the CS patients, the patient with both XP and CS, and the XP patient. It was proposed that patients with CS have defective repair of DNA which may be the cause of their retinal degeneration.

Retina-like sensor based on a lens array with a large field of view.

Science.gov (United States)

Fan, Fan; Hao, Qun; Cheng, Xuemin

2015-12-20

This paper puts forward a retina-like sensor based on a lens array, which can be used in conventional optical systems. This sensor achieves log-polar mapping by dividing the imaging optical system's image plane using a lens array. In this paper the mathematical model has been set up with the relative structural parameters. Also, the simulation experiments and parameter analysis have been discussed to verify the reliability of this system. From the experiment results, it can be seen that this sensor realized the log-polar mapping with the transformed image output. Each lens corresponded to a circular region in the image plane with no crossover between different fields of view of adjacent lenses. When the number of rings changed, the relative error did not significantly change, and this error could be reduced to 1% when the number of lenses in each ring was increased. The work widely enlarged the application of this kind of sensor, which will lay a theoretical foundation for retina-like sensors.

Changes of Retina Are Not Involved in the Genesis of Visual Hallucinations in Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Aleš Kopal

2015-01-01

Full Text Available Parkinson’s disease (PD is characterized by motor and nonmotor symptoms. Nonmotor symptoms include primarily visual hallucinations (VH. The aim of our study was to establish whether patients with PD and visual hallucinations (PDH+ have structural changes of retina detected by an optical coherence tomography (OCT in comparison with PD patients without visual hallucinations (PDH−. We examined 52 PD patients (18 with VH, 34 without VH and 15 age and sex matched healthy controls. Retinal nerve fiber layer (RNFL thickness and macular thickness and volume were assessed by OCT. Functional impairment of retina was assessed using 2.5% contrast sensitivity test. For OCT outcomes we analyzed 15 PDH+ and 15 PDH− subjects matched for age, gender, and PD duration. For contrast sensitivity we analyzed 8 pairs of patients matched for age, gender, and visual acuity. There was no significant difference in RNFL thickness and macular thickness and macular volume between 15 PDH+ and 15 PDH− subjects, and also between a group of 44 PD patients (both PDH+ and PDH− and 15 age and gender matched healthy controls. No significant difference was found for 2.5% contrast sensitivity test values between PDH+ and PDH− subjects. Therefore we conclude that functional and structural changes in retina play no role in genesis of VH in PD.

Bipolar Cell-Photoreceptor Connectivity in the Zebrafish (Danio rerio) Retina

Science.gov (United States)

Li, Yong N.; Tsujimura, Taro; Kawamura, Shoji; Dowling, John E.

2013-01-01

Bipolar cells convey luminance, spatial and color information from photoreceptors to amacrine and ganglion cells. We studied the photoreceptor connectivity of 321 bipolar cells in the adult zebrafish retina. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was inserted into whole-mounted transgenic zebrafish retinas to label bipolar cells. The photoreceptors that connect to these DiI-labeled cells were identified by transgenic fluorescence or their positions relative to the fluorescent cones, as cones are arranged in a highly-ordered mosaic: rows of alternating blue- (B) and ultraviolet-sensitive (UV) single cones alternate with rows of red- (R) and green-sensitive (G) double cones. Rod terminals intersperse among cone terminals. As many as 18 connectivity subtypes were observed, 9 of which – G, GBUV, RG, RGB, RGBUV, RGRod, RGBRod, RGBUVRod and RRod bipolar cells – accounted for 96% of the population. Based on their axon terminal stratification, these bipolar cells could be further sub-divided into ON, OFF, and ON-OFF cells. The dendritic spread size, soma depth and size, and photoreceptor connections of the 308 bipolar cells within the 9 common connectivity subtypes were determined, and their dendritic tree morphologies and axonal stratification patterns compared. We found that bipolar cells with the same axonal stratification patterns could have heterogeneous photoreceptor connectivity whereas bipolar cells with the same dendritic tree morphology usually had the same photoreceptor connectivity, although their axons might stratify on different levels. PMID:22907678

An experimental platform for systemic drug delivery to the retina.

LENUS (Irish Health Repository)

Campbell, Matthew

2009-10-20

Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders--major causes of world blindness--are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-\\/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment.

A mammalian melanopsin in the retina of a fresh water turtle, the red-eared slider (Trachemys scripta elegans).

Science.gov (United States)

Dearworth, James R; Selvarajah, Brian P; Kalman, Ross A; Lanzone, Andrew J; Goch, Abraham M; Boyd, Alison B; Goldberg, Laura A; Cooper, Lori J

2011-01-28

A mammalian-like melanopsin (Opn4m) has been found in all major vertebrate classes except reptile. Since the pupillary light reflex (PLR) of the fresh water turtle takes between 5 and 10 min to achieve maximum constriction, and since photosensitive retinal ganglion cells (ipRGCs) in mammals use Opn4m to control their slow sustained pupil responses, we hypothesized that a Opn4m homolog exists in the retina of the turtle. To identify its presence, retinal tissue was dissected from seven turtles, and total RNA extracted. Reverse transcriptase-polymerase chain reactions (RT-PCRs) were carried out to amplify gene sequences using primers targeting the highly conserved core region of Opn4m, and PCR products were analyzed by gel electrophoresis and sequenced. Sequences derived from a 1004-bp PCR product were compared to those stored in GenBank by the basic local alignment search tool (BLAST) algorithm and returned significant matches to several Opn4ms from other vertebrates including chicken. Quantitative real-time PCR (qPCR) was also carried out to compare expression levels of Opn4m in different tissues. The normalized expression level of Opn4m in the retina was higher in comparison to other tissue types: iris, liver, lung, and skeletal muscle. The results suggest that Opn4m exists in the retina of the turtle and provides a possible explanation for the presence of a slow PLR. The turtle is likely to be a useful model for further understanding the photoreceptive mechanisms in the retina which control the dynamics of the PLR. Copyright © 2010 Elsevier Ltd. All rights reserved.

Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function.

Science.gov (United States)

Kielczewski, Jennifer L; Horai, Reiko; Jittayasothorn, Yingyos; Chan, Chi-Chao; Caspi, Rachel R

2016-02-01

During chronic inflammation, tertiary lymphoid tissue (TLT) can form within an inflamed organ, including the CNS. However, little is known about TLT formation in the neuroretina. In a novel spontaneous autoimmune mouse model of uveitis (R161H), we identified well-organized lymphoid aggregates in the retina and examined them for TLT characteristics. Presence of immune cells, tissue-specific markers, and gene expression patterns typically associated with germinal centers and T follicular helper cells were examined using immunohistochemistry and gene analysis of laser capture microdissected retina. Our data revealed the retinal lymphoid structures contained CD4(+) T cells and B cells in well-defined zonal areas that expressed classic germinal center markers, peanut lectin (agglutinin) and GL-7. Gene expression analysis showed upregulation of T follicular helper cell markers, most notably CXCR5 and its ligand CXCL13, and immunohistochemical analysis confirmed CXCR5 expression, typically associated with CD4(+) T follicular helper cells. Highly organized stromal cell networks, a hallmark of organized lymphoid tissue, were also present. Positive staining for phospho-Zap70 in retina-specific T cells indicated CD4(+) T cells were being activated within these lymphoid structures. CD138(+)/B220(+) plasma cells were detected, suggesting the retinal lymphoid aggregates give rise to functional germinal centers, which produce Abs. Interestingly, eyes with lymphoid aggregates exhibited lower inflammatory scores by fundus examination and a slower initial rate of loss of visual function by electroretinography, compared with eyes without these structures. Our findings suggest that the lymphoid aggregates in the retina of R161H mice represent organized TLT, which impact the course of chronic uveitis.

Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

OpenAIRE

Katrin Hanken; Katrin Hanken; Mona Bosse; Kim Möhrke; Paul Eling; Andreas Kastrup; Andrea Antal; Helmut Hildebrandt; Helmut Hildebrandt

2016-01-01

Background: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anoda...

The ciliary marginal zone of the zebrafish retina: clonal and time-lapse analysis of a continuously growing tissue.

Science.gov (United States)

Wan, Yinan; Almeida, Alexandra D; Rulands, Steffen; Chalour, Naima; Muresan, Leila; Wu, Yunmin; Simons, Benjamin D; He, Jie; Harris, William A

2016-04-01

Clonal analysis is helping us understand the dynamics of cell replacement in homeostatic adult tissues (Simons and Clevers, 2011). Such an analysis, however, has not yet been achieved for continuously growing adult tissues, but is essential if we wish to understand the architecture of adult organs. The retinas of lower vertebrates grow throughout life from retinal stem cells (RSCs) and retinal progenitor cells (RPCs) at the rim of the retina, called the ciliary marginal zone (CMZ). Here, we show that RSCs reside in a niche at the extreme periphery of the CMZ and divide asymmetrically along a radial (peripheral to central) axis, leaving one daughter in the peripheral RSC niche and the other more central where it becomes an RPC. We also show that RPCs of the CMZ have clonal sizes and compositions that are statistically similar to progenitor cells of the embryonic retina and fit the same stochastic model of proliferation. These results link embryonic and postembryonic cell behaviour, and help to explain the constancy of tissue architecture that has been generated over a lifetime. © 2016. Published by The Company of Biologists Ltd.

Interaction between the soma and the axon terminal of horizontal cells in carp retina

NARCIS (Netherlands)

Kamermans, M.; van Dijk, B. W.; Spekreijse, H.

1990-01-01

In teleost retina, the receptive fields of horizontal cell axon terminals have a larger space constant than the receptive fields of the horizontal cell somata. Generally this difference in receptive field size is attributed to the cell coupling which is assumed to be stronger in the horizontal axon

A Perspective on the Müller Cell-Neuron Metabolic Partnership in the Inner Retina

DEFF Research Database (Denmark)

Toft-Kehler, A K; Skytt, D M; Kolko, Miriam

2017-01-01

between the vessels and neurons, Müller cells are responsible for the functional and metabolic support of the surrounding neurons. As a consequence of major energy demands in the retina, high levels of glucose are consumed and processed by Müller cells. The present review provides a perspective...

Photophysical properties of xanthophylls in carotenoproteins from human retinas.

Science.gov (United States)

Billsten, Helena H; Bhosale, Prakash; Yemelyanov, Alexander; Bernstein, Paul S; Polívka, Tomás

2003-08-01

The macula of the human retina contains high amounts of the xanthophyll carotenoids lutein and zeaxanthin [a mixture of (3R,3'R)-zeaxanthin and (3R,3'S-meso)-zeaxanthin]. Recently, it was shown that the uptake and the stabilization of zeaxanthin and lutein into the retina are likely to be mediated by specific xanthophyll-binding proteins (XBP). Here, we have used femtosecond pump-probe spectroscopy to study the dynamics of the S1 state of these xanthophylls in xanthophyll-enriched and native XBP. The results from the native XBP and the enriched XBP were then compared with those for carotenoids in organic solvents and in detergent micelles. Steady-state and transient absorption spectra show that the incorporation of xanthophylls into the protein causes a redshift of the spectra, which is stronger for lutein than for zeaxanthin. The transient absorption spectra further indicate that a part of the xanthophylls remains unbound in the xanthophyll-enriched XBP. The transient absorption spectra of the native XBP prove the presence of both xanthophylls in native XBP. Although the S1 lifetime of lutein does not exhibit any changes when measured in solution, micelles or XBP, we have observed the influence of the environment on the S1 lifetime of meso-zeaxanthin, which has a longer (12 ps) lifetime in XBP than in solution (9 ps). The most pronounced effect was found for vibrational relaxation in the S1 state, which is significantly slower for xanthophylls in XBP compared with micelles and solution. This effect is more pronounced for meso-zeaxanthin, suggesting a specific site of binding of this carotenoid to XBP.

Transscleral diode laser retinopexy in retinal reattachment surgery Retinopexia com laser de diodo transescleral na cirurgia de descolamento de retina

Directory of Open Access Journals (Sweden)

João Carlos de Miranda Gonçalves

2004-02-01

Full Text Available PURPOSE: Transscleral diode retinal photocoagulation (diopexy is becoming an accepted technique in the treatment of selected retinal diseases. The objective of this study is to evaluate diopexy technique in the production of adhesive chorioretinal lesions during the surgical treatment of the rhegmatogenous retinal detachment. METHODS: 25 patients with rhegmatogenous retinal detachment were enrolled in a prospective clinical-surgical study to evaluate the technique of transscleral diode laser photocoagulation to obtain adhesive chorioretinal lesions during retinal reattachment surgery. The surgery consisted of the placement of an exoplant silicon to produce a buckle effect combined with a drainage of subretinal fluid in most cases. RESULTS: By a mean follow-up of 10 months, 21 of 25 eyes had their retinas reattached after only one surgery with diopexy used in all cases. CONCLUSION: Transscleral diode laser photocoagulation was a technically easy, controlled, effective, reproducible and safe means of obtaining chorioretinal adhesion in retinal reattachment surgery.OBJETIVO: Fotocoagulação transescleral com laser de diodo (diopexia está se tornando técnica utilizada no tratamento de algumas doenças retinianas. O objetivo deste estudo é avaliar a técnica de diopexia na produção de lesões coriorretinianas aderentes durante o tratamento cirúrgico do descolamento de retina regmatogênico. MÉTODOS: Vinte e cinco pacientes com descolamento de retina regmatogênico participaram deste estudo clínico-cirúrgico prospectivo para avaliar a técnica de fotocoagulação com laser de diodo transescleral para obter lesões coriorretinianas aderentes durante a cirurgia de descolamento de retina. A cirurgia consistiu de colocação de explante de silicone para produzir efeito de introflexão escleral combinado com drenagem do líquido subretiniano na maioria dos casos. RESULTADOS: Após um período médio de seguimento de 10 meses, em 21 dos 25 olhos

RETINOBASE: a web database, data mining and analysis platform for gene expression data on retina

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Léveillard Thierry

2008-05-01

Full Text Available Abstract Background The retina is a multi-layered sensory tissue that lines the back of the eye and acts at the interface of input light and visual perception. Its main function is to capture photons and convert them into electrical impulses that travel along the optic nerve to the brain where they are turned into images. It consists of neurons, nourishing blood vessels and different cell types, of which neural cells predominate. Defects in any of these cells can lead to a variety of retinal diseases, including age-related macular degeneration, retinitis pigmentosa, Leber congenital amaurosis and glaucoma. Recent progress in genomics and microarray technology provides extensive opportunities to examine alterations in retinal gene expression profiles during development and diseases. However, there is no specific database that deals with retinal gene expression profiling. In this context we have built RETINOBASE, a dedicated microarray database for retina. Description RETINOBASE is a microarray relational database, analysis and visualization system that allows simple yet powerful queries to retrieve information about gene expression in retina. It provides access to gene expression meta-data and offers significant insights into gene networks in retina, resulting in better hypothesis framing for biological problems that can subsequently be tested in the laboratory. Public and proprietary data are automatically analyzed with 3 distinct methods, RMA, dChip and MAS5, then clustered using 2 different K-means and 1 mixture models method. Thus, RETINOBASE provides a framework to compare these methods and to optimize the retinal data analysis. RETINOBASE has three different modules, "Gene Information", "Raw Data System Analysis" and "Fold change system Analysis" that are interconnected in a relational schema, allowing efficient retrieval and cross comparison of data. Currently, RETINOBASE contains datasets from 28 different microarray experiments performed

Dopamine D4 Receptor Counteracts Morphine-Induced Changes in µ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen

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Diana Suárez-Boomgaard

2014-01-01

Full Text Available The mu opioid receptor (MOR is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [35S]GTPγS autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D4 receptor (D4R agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to Gi/0 protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine.

Quantitative Assessment of Microstructural Changes of the Retina in Infants With Congenital Zika Syndrome.

Science.gov (United States)

Aleman, Tomas S; Ventura, Camila V; Cavalcanti, Milena M; Serrano, Leona W; Traband, Anastasia; Nti, Akosua A; Gois, Adriana L; Bravo-Filho, Vasco; Martins, Thayze T; Nichols, Charles W; Maia, Mauricio; Belfort, Rubens

2017-10-01

A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS). To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment. This case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from January 1 to March 17, 2016, for patients with CZS and from May 4, 2015, to April 23, 2016, for patients with cblC deficiency. The SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles. Eight infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years) were included in the analysis. All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (<30% of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer

Balanced steady state free precession for arterial spin labeling MRI: Initial experience for blood flow mapping in human brain, retina, and kidney.

Science.gov (United States)

Park, Sung-Hong; Wang, Danny J J; Duong, Timothy Q

2013-09-01

We implemented pseudo-continuous ASL (pCASL) with 2D and 3D balanced steady state free precession (bSSFP) readout for mapping blood flow in the human brain, retina, and kidney, free of distortion and signal dropout, which are typically observed in the most commonly used echo-planar imaging acquisition. High resolution functional brain imaging in the human visual cortex was feasible with 3D bSSFP pCASL. Blood flow of the human retina could be imaged with pCASL and bSSFP in conjunction with a phase cycling approach to suppress the banding artifacts associated with bSSFP. Furthermore, bSSFP based pCASL enabled us to map renal blood flow within a single breath hold. Control and test-retest experiments suggested that the measured blood flow values in retina and kidney were reliable. Because there is no specific imaging tool for mapping human retina blood flow and the standard contrast agent technique for mapping renal blood flow can cause problems for patients with kidney dysfunction, bSSFP based pCASL may provide a useful tool for the diagnosis of retinal and renal diseases and can complement existing imaging techniques. Copyright © 2013 Elsevier Inc. All rights reserved.

Buspirone Counteracts MK-801-Induced Schizophrenia-Like Phenotypes through Dopamine D3 Receptor Blockade

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Torrisi, Sebastiano Alfio; Salomone, Salvatore; Geraci, Federica; Caraci, Filippo; Bucolo, Claudio; Drago, Filippo; Leggio, Gian Marco

2017-01-01

Background: Several efforts have been made to develop effective antipsychotic drugs. Currently, available antipsychotics are effective on positive symptoms, less on negative symptoms, but not on cognitive impairment, a clinically relevant dimension of schizophrenia. Drug repurposing offers great advantages over the long-lasting, risky and expensive, de novo drug discovery strategy. To our knowledge, the possible antipsychotic properties of buspirone, an azapirone anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial agonist, have not been extensively investigated despite its intriguing pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R) antagonist activity. Multiple lines of evidence point to D3R as a valid therapeutic target for the treatment of several neuropsychiatric disorders including schizophrenia. In the present study, we tested the hypothesis that buspirone, behaving as dopamine D3R antagonist, may have antipsychotic-like activity. Materials and Methods: Effects of acute administration of buspirone was assessed on a wide-range of schizophrenia-relevant abnormalities induced by a single administration of the non-competitive NMDAR antagonist MK-801, in both wild-type mice (WT) and D3R-null mutant mice (D3R-/-). Results: Buspirone (3 mg⋅kg-1, i.p.) was devoid of cataleptogenic activity in itself, but resulted effective in counteracting disruption of prepulse inhibition (PPI), hyperlocomotion and deficit of temporal order recognition memory (TOR) induced by MK-801 (0.1 mg⋅kg-1, i.p.) in WT mice. Conversely, in D3R-/- mice, buspirone was ineffective in preventing MK-801-induced TOR deficit and it was only partially effective in blocking MK-801-stimulated hyperlocomotion. Conclusion: Taken together, these results indicate, for the first time, that buspirone, might be a potential therapeutic medication for the treatment of schizophrenia. In particular, buspirone, through its D3R antagonist activity, may be

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

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Locri, Filippo; Amato, Rosario; Marsili, Stefania; Rusciano, Dario; Bagnoli, Paola

2018-01-01

Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role. PMID:29517994

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

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Massimo Dal Monte

2018-03-01

Full Text Available Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON and is an initial symptom of multiple sclerosis (MS. Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG, were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM, a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®, a balanced mixture of fatty acids (FAs, counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role.

Localization of diacylglycerol lipase alpha and monoacylglycerol lipase during postnatal development of the rat retina

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Bruno eCécyre

2014-12-01

Full Text Available In recent decades, there has been increased interest in the physiological roles of the endocannabinoid (eCB system and its receptors, the cannabinoid receptor types 1 (CB1R and 2 (CB2R. Exposure to cannabinoids during development results in neurofunctional alterations, which implies that the eCB system is involved in the developmental processes of the brain. Because of their lipophilic nature, eCBs are synthesized on demand and are not stored in vesicles. Consequently, the enzymes responsible for their synthesis and degradation are key regulators of their physiological actions. Therefore, knowing the localization of these enzymes during development is crucial for a better understanding of the role played by eCBs during the formation of the central nervous system.In this study, we investigated the developmental protein localization of the synthesizing and catabolic enzymes of the principal eCB, 2-arachidonoylglycerol (2-AG in the retinas of young and adult rats. The distribution of the enzymes responsible for the synthesis (DAGLα and the degradation (MAGL of 2-AG was determined for every retinal cell type from birth to adulthood. Our results indicate that DAGLα is present early in postnatal development. It is highly expressed in photoreceptor, horizontal, amacrine, and ganglion cells. MAGL appears later during the development of the retina and its presence is limited to amacrine and Müller cells. Overall, these results suggest that 2-AG is strongly present in early retinal development and might be involved in the regulation of the structural and functional maturation of the retina.

Alpha-Tocopherol Counteracts the Cytotoxicity Induced by Ochratoxin A in Primary Porcine Fibroblasts

DEFF Research Database (Denmark)

Fusi, Elenora; Rebucci, Raffaella; Pecorini, Chiara

2010-01-01

The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in counteracting its toxicity....... Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM α-tocopherol significantly (P tocopherol...

High-Intensity Interval Training as a Tool for Counteracting Dyslipidemia in Women.

Science.gov (United States)

Alvarez, Cristian; Ramirez-Campillo, Rodrigo; Martinez-Salazar, Cristian; Castillo, Angélica; Gallardo, Francisco; Ciolac, Emmanuel Gomes

2018-05-01

Sedentary overweight or obese adult (agehigh-intensity interval training (HIIT) program. Triglycerides reduced significantly ( P high-density lipoprotein increased ( P body composition improved ( P <0.05) in all groups. The HIIT program was effective for restoring lipid profile of DYS and DYSHG, and fasting glucose of DYSHG to levels similar to those of CON, with a weekly time commitment 25% to 56% lower than the minimum recommended in current exercise guidelines. These findings suggest that HIIT may be a time-efficient intervention for counteracting dyslipidemia. © Georg Thieme Verlag KG Stuttgart · New York.

Testing the ability of non-methylamine osmolytes present in kidney cells to counteract the deleterious effects of urea on structure, stability and function of proteins.

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Sheeza Khan

Full Text Available Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D (o and functional activity parameters (K m and k cat of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea] ratio, (ii any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea] ratios for RNase-A, lysozyme and α-lactalbumin, respectively.

Is adding a new class of cones to the retina sufficient to cure color-blindness?

NARCIS (Netherlands)

Cornelissen, F.W.; Brenner, E.

2015-01-01

New genetic methods have made it possible to substitute cone pigments in the retinas of adult nonhuman primates. Doing so influences the animals' visual abilities, demonstrating that the gene therapy was effective. However, we argue that no studies conducted so far have unambiguously demonstrated

Is adding a new class of cones to the retina sufficient to cure color-blindness?

NARCIS (Netherlands)

Cornelissen, Frans W.; Brenner, Eli

New genetic methods have made it possible to substitute cone pigments in the retinas of adult nonhuman primates. Doing so influences the animals' visual abilities, demonstrating that the gene therapy was effective. However, we argue that no studies conducted so far have unambiguously demonstrated

The characteristics of the pediatric model for counteracting obesity in Serbia

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Banićević Miloš

2012-01-01

Full Text Available Basic data on the establishment, features and results of the health care system for children and adolescents in the Republic of Serbia during the period 1950-1990 are given in the introductory remarks. Enormous pressure for the change of the health sector ownership and the profile of physicians in the primary pediatric care in the last decade of 20th century and at the beginning of 21st century is also emphasized. The destructive consequences of the sanctions of international community (1992-1995, NATO aggression (1999 and the change of the political system in Serbia (2000 caused the huge loss of gross domestic product, increase of the unemployment and poverty rates, and the decrease of the health expenditure rate to unsustainable levels (200-300 USD per capita. In spite of all misfortunes, Pediatric Association of Serbia, in response to the global obesity epidemic, offered in 2007 to the Ministry of health and the National Institute for health insurance the Project 'The prevention and treatment of obesity in children and adolescents in Serbia', as the pediatric chapter for future National strategy for counteracting obesity. The Project, ie the pediatric model for counteracting obesity is funded on the features of the health care system for children and adolescents in our country. The solidarity of the society and the continuous education of health care workers, adolescents and their parents about the significance of obesity epidemic are, in our conviction, key factors for the strengthening of adolescent's conscience on individual responsibility for own health as the prerequisite for successful control of obesity epidemic in adolescents.

Photopic spectral sensitivities of the red and the yellow field of the pigeon retina

NARCIS (Netherlands)

Wortel, J.F.; Wubbels, R.J.; Nuboer, J.F.W.

1984-01-01

The spectral sensitivities of the red field and the yellow field in the retina of the homing pigeon (Columba Livia) were determined on the basis of ERG responses. Between 450 and 550 nm the relative spectral sensitivity of the yellow field turned out to be higher than that of the red field. The

Restricted expression of Neuroglobin in the mouse retina and co-localization with Melanopsin and Tyrosine Hydroxylase

International Nuclear Information System (INIS)

Hundahl, C.A.; Fahrenkrug, J.; Luuk, H.; Hay-Schmidt, A.; Hannibal, J.

2012-01-01

Highlights: ► Restricted Neuroglobin expression in the mouse retina. ► Antibody validation using Neuroglobin-null mice. ► Co-expression of Neuroglobin with Melanopsin and tyrosine hydroxylase. ► No effect of Neuroglobin deficiency on neuronal survival. -- Abstract: Neuroglobin (Ngb), a neuronal specific oxygen binding heme-globin, reported to be expressed at high levels in most layers of the murine retina. Ngb’s function is presently unknown, but based on its high expression level and oxygen binding capabilities Ngb was proposed to function as an oxygen reservoir facilitating oxygen metabolism in highly active neurons or to function as a neuroprotectant. In the present study, we re-examined the expression pattern of Ngb in the retina using a highly validated antibody. Furthermore, intactness of retino-hypothalamic projections and the retinal expression level of Melanopsin and Tyrosine Hydroxylase were investigated in Ngb-null mice. Ngb-immunoreactivity was found in a few neurons of the ganglion cell and inner nuclear layers co-expressing Melanopsin and Tyrosine Hydroxylase, respectively. Ngb deficiency neither affected the level of Melanopsin and Tyrosine Hydroxylase proteins nor the intactness of PACAP-positive retinohypothalamic projections in the suprachiasmatic nucleus. Based on the present results, it seems unlikely that Ngb could have a major role in retinal oxygen homeostasis and neuronal survival under normal conditions. The present study suggests that a number of previously published reports have relied on antibodies with dubious specificity.

Pharmacological and biochemical characterization of the D-1 dopamine receptor mediating acetylcholine release in rabbit retina

International Nuclear Information System (INIS)

Hensler, J.G.; Cotterell, D.J.; Dubocovich, M.L.

1987-01-01

Superfusion with dopamine (0.1 microM-10 mM) evokes calcium-dependent [ 3 H]acetylcholine release from rabbit retina labeled in vitro with [ 3 H]choline. This effect is antagonized by the D-1 dopamine receptor antagonist SCH 23390. Activation or blockade of D-2 dopamine, alpha-2 or beta receptors did not stimulate or attenuate the release of [ 3 H]acetylcholine from rabbit retina. Dopamine receptor agonists evoke the release of [ 3 H]acetylcholine with the following order of potency: apomorphine ≤ SKF(R)82526 3 H]acetylcholine: SCH 23390 (IC50 = 1 nM) 3 H]acetylcholine release is characteristic of the D-1 dopamine receptor. These potencies were correlated with the potencies of dopamine receptor agonists and antagonists at the D-1 dopamine receptor in rabbit retina as labeled by [ 3 H]SCH 23390, or as determined by adenylate cyclase activity. [ 3 H]SCH 23390 binding in rabbit retinal membranes was stable, saturable and reversible. Scatchard analysis of [ 3 H]SCH 23390 saturation data revealed a single high affinity binding site (Kd = 0.175 +/- 0.002 nM) with a maximum binding of 482 +/- 12 fmol/mg of protein. The potencies of dopamine receptor agonists to stimulate [ 3 H]acetylcholine release were correlated with their potencies to stimulate adenylate cyclase (r = 0.784, P less than .05, n = 7) and with their affinities at [ 3 H]SCH 23390 binding sites (r = 0.755, P < .05, n = 8)

Restricted expression of Neuroglobin in the mouse retina and co-localization with Melanopsin and Tyrosine Hydroxylase

Energy Technology Data Exchange (ETDEWEB)

Hundahl, C.A., E-mail: c.hundahl@gmail.com [Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark); Centre of Excellence for Translational Medicine, University of Tartu, Tartu (Estonia); Department of Physiology, University of Tartu, Tartu (Estonia); Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen (Denmark); Fahrenkrug, J. [Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark); Luuk, H. [Centre of Excellence for Translational Medicine, University of Tartu, Tartu (Estonia); Department of Physiology, University of Tartu, Tartu (Estonia); Hay-Schmidt, A. [Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen (Denmark); Hannibal, J. [Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark)

2012-08-17

Highlights: Black-Right-Pointing-Pointer Restricted Neuroglobin expression in the mouse retina. Black-Right-Pointing-Pointer Antibody validation using Neuroglobin-null mice. Black-Right-Pointing-Pointer Co-expression of Neuroglobin with Melanopsin and tyrosine hydroxylase. Black-Right-Pointing-Pointer No effect of Neuroglobin deficiency on neuronal survival. -- Abstract: Neuroglobin (Ngb), a neuronal specific oxygen binding heme-globin, reported to be expressed at high levels in most layers of the murine retina. Ngb's function is presently unknown, but based on its high expression level and oxygen binding capabilities Ngb was proposed to function as an oxygen reservoir facilitating oxygen metabolism in highly active neurons or to function as a neuroprotectant. In the present study, we re-examined the expression pattern of Ngb in the retina using a highly validated antibody. Furthermore, intactness of retino-hypothalamic projections and the retinal expression level of Melanopsin and Tyrosine Hydroxylase were investigated in Ngb-null mice. Ngb-immunoreactivity was found in a few neurons of the ganglion cell and inner nuclear layers co-expressing Melanopsin and Tyrosine Hydroxylase, respectively. Ngb deficiency neither affected the level of Melanopsin and Tyrosine Hydroxylase proteins nor the intactness of PACAP-positive retinohypothalamic projections in the suprachiasmatic nucleus. Based on the present results, it seems unlikely that Ngb could have a major role in retinal oxygen homeostasis and neuronal survival under normal conditions. The present study suggests that a number of previously published reports have relied on antibodies with dubious specificity.

La complejidad de las distrofias hereditarias de la retina: un obstáculo y un reto

OpenAIRE

Martín Nieto, José

2014-01-01

ACTO conjunto de FARPE-FUNDALUCE con la SEBBM en el marco de su XXXVII Congreso. Conferencia: La complejidad de las distrofias hereditarias de la retina: Un obstáculo y un reto (José Martín Nieto).

Diurnal rodents as animal models of human central vision: characterisation of the retina of the sand rat Psammomys obsesus.

Science.gov (United States)

Saïdi, Tounès; Mbarek, Sihem; Chaouacha-Chekir, Rafika Ben; Hicks, David

2011-07-01

Cone photoreceptor-based central vision is of paramount importance in human eyesight, and the increasing numbers of persons affected by macular degeneration emphasizes the need for relevant and amenable animal models. Although laboratory mice and rats have provided valuable information on retinal diseases, they have inherent limitations for studies on macular pathology. In the present study, we extend our recent analyses of diurnal murid rodents to demonstrate that the sand rat Psammomys obesus has a remarkably cone-rich retina, and represents a useful adjunct to available animal models of central vision. Adult P. obesus were captured and transferred to animal facilities where they were maintained under standard light/dark cycles. Animals were euthanised and their eyes enucleated. Tissue was either fixed in paraformaldehyde and prepared for immunohistochemistry, or solubilized in lysis buffer and separated by SDS-PAGE and subjected to western blot analysis. Samples were labelled with a battery of antibodies against rod and cone photoreceptors, inner retinal neurones, and glia. P. obesus showed a high percentage of cones, 41% of total photoreceptor numbers in both central and peripheral retina. They expressed multiple cone-specific proteins, including short and medium-wavelength opsin and cone transducin. A second remarkable feature of the retina concerned the horizontal cells, which expressed high levels of glial fibrillar acidic protein and occludin, two proteins which are not seen in other species. The retina of P. obesus displays high numbers of morphologically and immunologically identifiable cones which will facilitate analysis of cone pathophysiology in this species. The unusual horizontal cell phenotype may be related to the cone distribution or to an alternative facet of the animals lifestyle.

Impact of application of bio-amniotic membrane immersed in 5-fluorouracil solution in trabeculectomy on rabbit retina

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Chenming Zhang

2013-01-01

Full Text Available Background : To observe the impact of application of bio-amniotic membrane immersed in 5-fluorouracil solution in trabeculectomy on the retina in a rabbit model. Materials and Methods : Healthy white New Zealand rabbits were randomly assigned into three groups with 20 in each group. Bio-amniotic membranes of 4 × 5 mm immersed in either physiological saline/water for 10 min, or 25 mg/mL 5-fluorouracil solution for 5 and 10 min, respectively, were applied on rabbit eyes during trabeculectomy. At 7, 14, 21, and 28 days of postoperation, five rabbits from each group were examined with electroretinogram (ERG. After being examined for eye pressure and bleb morphology, rabbits were sacrificed by air embolism and their retinas were collected and examined by transmission electron microscopy (TEM. In addition, 5-fluorouracil amount in bio-amniotic membranes was measured using high-performance liquid chromatography. Results: Each bio-amniotic membrane could absorb 59.004 μg and 75.828 μg 5-fluorouracil after being immersed in 5-fluorouracil solution for 5 and 10 min, respectively. Application of these bio-amniotic membranes in trabeculectomy could promote the formation of well-functioning bleb and maintain intraocular pressure, although it had no effect on retina structures as examined with ERG and TEM. Conclusion: Application of 5-FU soaked bio-amniotic membrane in rabbit eye trabeculectomy is effective and safe.

Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

Science.gov (United States)

Tao, Zui; Zhao, Chen; Jian, Qian; Gillies, Mark; Xu, Haiwei; Yin, Zheng Qin

2016-01-01

Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats. PMID:27384999

1 kHz 2D Visual Motion Sensor Using 20 × 20 Silicon Retina Optical Sensor and DSP Microcontroller.

Science.gov (United States)

Liu, Shih-Chii; Yang, MinHao; Steiner, Andreas; Moeckel, Rico; Delbruck, Tobi

2015-04-01

Optical flow sensors have been a long running theme in neuromorphic vision sensors which include circuits that implement the local background intensity adaptation mechanism seen in biological retinas. This paper reports a bio-inspired optical motion sensor aimed towards miniature robotic and aerial platforms. It combines a 20 × 20 continuous-time CMOS silicon retina vision sensor with a DSP microcontroller. The retina sensor has pixels that have local gain control and adapt to background lighting. The system allows the user to validate various motion algorithms without building dedicated custom solutions. Measurements are presented to show that the system can compute global 2D translational motion from complex natural scenes using one particular algorithm: the image interpolation algorithm (I2A). With this algorithm, the system can compute global translational motion vectors at a sample rate of 1 kHz, for speeds up to ±1000 pixels/s, using less than 5 k instruction cycles (12 instructions per pixel) per frame. At 1 kHz sample rate the DSP is 12% occupied with motion computation. The sensor is implemented as a 6 g PCB consuming 170 mW of power.

[Evaluation of fundus autofluorescence in hereditary retinal diseases using Heidelberg Retina Angiograph2].

Science.gov (United States)

Côco, Monique; Baba, Natalia Tamie; Sallum, Juliana Maria Ferraz

2007-01-01

To define characteristics of the fundus autofluorescence examination, verifying usefulness in the diagnosis and care of hereditary retinal diseases. 28 patients, adults, divided equally into four groups with diagnoses of Stargardt macular dystrophy, cone dystrophy, retinitis pigmentosa and healthy volunteers for the establishment of the normality pattern. An average of nine images with the filter for fluorescein angiography was obtained for the formation of the image autofluorescence using Heidelberg Retina Angiograph2. The images of each group of patients were analyzed to verify common characteristics. The fundus autofluorescence of healthy volunteers showed the foveal area darker than the surrounding retina. The images of Stargardt macular dystrophy, in general, presented an oval central lesion, with reduced autofluorescence. The main alterations of the autofluorescence in patients with cone dystrophy were reduced foveal autofluorescence with a parafoveal ring of increased autofluorescence. In general, the images of retinitis pigmentosa showed outlying pigments with reduced autofluorescence, and of the foveal area, in some cases disorganization or reduced autofluorescence. The study showed the existence of patterns of fundus autofluorescence in the hereditary retinal diseases that allow the diagnosis and better interpretation of the pathogenesis of these diseases.

Herniation of the retina in the central macula in an adult after iridocyclitis.

Science.gov (United States)

Guo, Qing; Pi, Yuli; Gao, Ting

2014-09-01

To report an unusual case of retinal hernia in the central macula in an adult after iridocyclitis. We report a case of a 46-year-old male who presented with blurred vision 2 weeks after complete resolution of acute iridocyclitis. Anterior segment and vitreous body examinations were unremarkable. Yellowish spots in the macular area were observed. Spectral domain optical coherence tomography (SD-OCT) imaging of the macula showed loss of the inner segment/outer segment (IS/OS) photoreceptor junction, with irregularity of the retinal pigment epithelium (RPE), and a V-shaped hernia of the retina into the choroid. The macular lesions emerged as mild window defects on fluorescein angiography and were visualized as hypofluorescent patches on all-phase indocyanine green angiography. At a one month follow-up, the best-corrected visual acuity improved to 20/20, which was followed by partial restoration of the IS/OS line, but a V-shaped hernia of the retina remained unchanged on SD-OCT. Ophthalmologists should be alert to the changes in OCT of the macula in patients after iridocyclitis and further research on the cause and possible predisposing factors for retinal herniation is warranted.

Characterization of Pax2 expression in the goldfish optic nerve head during retina regeneration.

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Marta Parrilla

Full Text Available The Pax2 transcription factor plays a crucial role in axon-guidance and astrocyte differentiation in the optic nerve head (ONH during vertebrate visual system development. However, little is known about its function during regeneration. The fish visual system is in continuous growth and can regenerate. Müller cells and astrocytes of the retina and ONH play an important role in these processes. We demonstrate that pax2a in goldfish is highly conserved and at least two pax2a transcripts are expressed in the optic nerve. Moreover, we show two different astrocyte populations in goldfish: Pax2(+ astrocytes located in the ONH and S100(+ astrocytes distributed throughout the retina and the ONH. After peripheral growth zone (PGZ cryolesion, both Pax2(+ and S100(+ astrocytes have different responses. At 7 days after injury the number of Pax2(+ cells is reduced and coincides with the absence of young axons. In contrast, there is an increase of S100(+ astrocytes in the retina surrounding the ONH and S100(+ processes in the ONH. At 15 days post injury, the PGZ starts to regenerate and the number of S100(+ astrocytes increases in this region. Moreover, the regenerating axons reach the ONH and the pax2a gene expression levels and the number of Pax2(+ cells increase. At the same time, S100(+/GFAP(+/GS(+ astrocytes located in the posterior ONH react strongly. In the course of the regeneration, Müller cell vitreal processes surrounding the ONH are primarily disorganized and later increase in number. During the whole regenerative process we detect a source of Pax2(+/PCNA(+ astrocytes surrounding the posterior ONH. We demonstrate that pax2a expression and the Pax2(+ astrocyte population in the ONH are modified during the PGZ regeneration, suggesting that they could play an important role in this process.

Müller cells express the cannabinoid CB2 receptor in the vervet monkey retina

DEFF Research Database (Denmark)

Bouskila, Joseph; Javadi, Pasha; Casanova, Christian

2013-01-01

The presence of the cannabinoid receptor type 1 (CB1R) has been largely documented in the rodent and primate retinae in recent years. There is, however, some controversy concerning the presence of the CB2 receptor (CB2R) within the central nervous system. Only recently, CB2R has been found in the...

Effect of Saffron on Metabolic Profile and Retina in Apolipoprotein E-Knockout Mice Fed a High-Fat Diet.

Science.gov (United States)

Doumouchtsis, Evangelos K; Tzani, Aspasia; Doulamis, Ilias P; Konstantopoulos, Panagiotis; Laskarina-Maria, Korou; Agrogiannis, Georgios; Agapitos, Emmanouil; Moschos, Marilita M; Kostakis, Alkiviadis; Perrea, Despina N

2017-09-22

Saffron is a spice that has been traditionally used as a regimen for a variety of diseases due to its potent antioxidant attributes. It is well documented that impaired systemic oxidative status is firmly associated with diverse adverse effects including retinal damage. The aim of this study was to investigate the role of saffron administration against the retinal damage in apoE -/- mice fed a high-fat diet, since they constitute a designated experimental model susceptible to oxidative stress. Twenty-one mice were allocated into three groups: Group A (control, n = 7 c57bl/6 mice) received standard chow diet; Group B (high-fat, n = 7 apoE -/- mice) received a high-fat diet; and Group C (high-fat and saffron, n = 7 apoE -/- mice) received a high-fat diet and saffron (25 mg/kg/d) through their drinking water. The duration of the study was 20 weeks. Lipidemic profile, glucose, C-reactive protein (CRP), and total oxidative capacity (PerOX) were measured in blood serum. Histological analysis of retina was also conducted. Administration of saffron resulted in enhanced glycemic control and preservation of retinal thickness when compared with apoE -/- mice fed a high-fat diet. The outcomes of the study suggest the potential protective role of saffron against retinal damage induced by oxidative stress. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn.

Artificial Retina Project: Final Report for CRADA ORNL 01-0625

Energy Technology Data Exchange (ETDEWEB)

Greenbaum, E; Little, J [Second Sight Medical Products

2011-09-01

The U.S. Department of Energy’s Artificial Retina Project is a collaborative, multi-institutional effort to develop an implantable microelectronic retinal prosthesis that restores useful vision to people blinded by retinal diseases. The ultimate goal of the project is to restore reading ability, facial recognition, and unaided mobility in people with retinitis pigmentosa and age-related macular degeneration. The project taps into the unique research technologies and resources developed at DOE national laboratories to surmount the many technical challenges involved with developing a safe, effective, and durable product. The research team includes six DOE national laboratories, four universities, and private industry.

Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina.

Science.gov (United States)

Wang, Tzu-Ming; Holzhausen, Lars C; Kramer, Richard H

2014-02-01

The reciprocal synapse between photoreceptors and horizontal cells underlies lateral inhibition and establishes the antagonistic center-surround receptive fields of retinal neurons to enhance visual contrast. Despite decades of study, the signal mediating the negative feedback from horizontal cells to cones has remained under debate because the small, invaginated synaptic cleft has precluded measurement. Using zebrafish retinas, we show that light elicits a change in synaptic proton concentration with the correct magnitude, kinetics and spatial dependence to account for lateral inhibition. Light, which hyperpolarizes horizontal cells, causes synaptic alkalinization, whereas activating an exogenously expressed ligand-gated Na(+) channel, which depolarizes horizontal cells, causes synaptic acidification. Whereas acidification was prevented by blocking a proton pump, re-alkalinization was prevented by blocking proton-permeant ion channels, suggesting that distinct mechanisms underlie proton efflux and influx. These findings reveal that protons mediate lateral inhibition in the retina, raising the possibility that protons are unrecognized retrograde messengers elsewhere in the nervous system.

Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

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Le Sun

Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

Retina tissue engineering by conjunctiva mesenchymal stem cells encapsulated in fibrin gel: Hypotheses on novel approach to retinal diseases treatment.

Science.gov (United States)

Soleimannejad, Mostafa; Ebrahimi-Barough, Somayeh; Nadri, Samad; Riazi-Esfahani, Mohammad; Soleimani, Masoud; Tavangar, Seyed Mohammad; Ai, Jafar

2017-04-01

Retinitis pigmentosa (RP) and age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision. Our hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders. In this idea, we describe a novel approach for retina tissue engineering with differentiation of conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells in fibrin gel with induction medium contain taurine. For assessment of differentiation, immunocytochemistry and real time PCR are used for the expression of Rhodopsin, RPE65, Nestin as differentiated photoreceptor cell markers in 2D and 3D culture. The results show that fibrin gel will offer a proper 3D scaffold for CJMSCs derived photoreceptor cell-like cells. Application of immune-privileged, readily available sources of adult stem cells like human conjunctiva stem cells with fibrin gel would be a promising strategy to increase the number of photoreceptor progenitor cells and promote involuntary angiogenesis needed in retina layer repair and regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

Science.gov (United States)

Kamal, Amer; Van der Harst, Johanneke E; Kapteijn, Chantal M; Baars, Annemarie J M; Spruijt, Berry M; Ramakers, Geert M J

2010-04-01

Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

Depletion of the Third Complement Component Ameliorates Age-Dependent Oxidative Stress and Positively Modulates Autophagic Activity in Aged Retinas in a Mouse Model

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Dorota Rogińska

2017-01-01

Full Text Available The aim of the study was to investigate the influence of complement component C3 global depletion on the biological structure and function of the aged retina. In vivo morphology (OCT, electrophysiological function (ERG, and the expression of selected oxidative stress-, apoptosis-, and autophagy-related proteins were assessed in retinas of 12-month-old C3-deficient and WT mice. Moreover, global gene expression in retinas was analyzed by RNA arrays. We found that the absence of active C3 was associated with (1 alleviation of the age-dependent decrease in retinal thickness and gradual deterioration of retinal bioelectrical function, (2 significantly higher levels of antioxidant enzymes (catalase and glutathione reductase and the antiapoptotic survivin and Mcl-1/Bak dimer, (3 lower expression of the cellular oxidative stress marker—4HNE—and decreased activity of proapoptotic caspase-3, (4 ameliorated retinal autophagic activity with localization of ubiquitinated protein conjugates commonly along the retinal pigment epithelium (RPE layer, and (5 significantly increased expression of several gene sets associated with maintenance of the physiological functions of the neural retina. Our findings shed light on mechanisms of age-related retinal alterations by identifying C3 as a potential therapeutic target for retinal aging.

The relation between serum lipids and lutein and zeaxanthin in the serum and retina: results from cross-sectional, case-control and case study designs

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Renzi Lisa M

2012-02-01

Full Text Available Abstract Background The xanthophyll carotenoids lutein (L and zeaxanthin (Z are found in and around the macula of the primate retina, where they are termed macular pigment (MP. Dietary L and Z are absorbed with fat in the gut and transported on lipoproteins to the retina. Both MP and serum lipoproteins have been related to risk for neurodegenerative diseases such as age-related macular degeneration (AMD. L and Z are carried on both HDL (related to reduced risk of AMD and LDL (related to increased risk. The purpose of this set of studies was to analyze the relation between L and Z in the serum and retina with the circulating lipid profile. Methods In all experiments, lipoproteins were measured enzymatically from plasma, and MP optical density (MPOD was measured using customized heterochromatic flicker photometry. Experiment 1: Relations between serum L and Z, MPOD and lipoprotein levels. 108 young, healthy subjects (M = 23.2, SD = 4.12 years participated. Lipoprotein levels and MPOD were measured. In a subset of 66 participants, serum L and Z levels were also measured using high-performance liquid chromatography. Experiment 2: Relations between lipoprotein levels and MPOD in statin users. 20 subjects (M = 58.05, SD = 11.08 years taking statin medication and 20 subjects (M = 57.95, SD = 11.03 years not taking satin were recruited for participation. MPOD and lipoprotein levels were measured. Experiment 3: lowering lipoprotein levels to impact MPOD. One individual (aged 41 years with high MP density adhered first to an atorvastatin regimen, then, after a wash-out period, to a rosuvastatin regimen. Results Experiment 1: HDL were significantly (p r = 0.33, to serum L (r = 0.36 and to serum Z (r = 0.26. MPOD was also significantly related to total cholesterol (r = 0.19. Experiment 2: MPOD was not lower in statin users when compared to matched non-statin users, but MPOD decreased significantly with increased duration of statin use (r = −0

Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons

International Nuclear Information System (INIS)

Kyriakis, J.M.; Hausman, R.E.; Peterson, S.W.

1987-01-01

The effect of insulin on the appearance of the enzyme choline acetyltransferase in embryonic chicken retina neurons cultured in defined medium was studied. In the presence of a minimal level of insulin (1 ng/ml), ChoAcT activity increased with time in culture. A correspondence between the insulin concentration in the defined medium (1-100 ng/ml) and both the rate of increase and maximum attained level of ChoAcT activity was observed. Maximal ChoAcT activity was 2- to 3-fold greater in cells cultured in the presence of 100 ng of insulin per ml than in cells cultured in the presence of 1 ng of insulin per ml. To elicit maximum ChoAcT activity, insulin at 100 ng/ml was required in the medium for only the first 4 days of the culture period, at which time insulin could be reduced to maintenance levels (10 ng/ml) without affecting ChoAcT activity. Insulin binding assays performed during a 7-day culture period revealed that irrespective of the 125 I-insulin concentration in the medium during culture, cell-surface insulin receptors decreased by ≅ 90% between 4 and 7 days in culture. This decrease in insulin binding corresponded to the observed decrease in the sensitivity of ChoAcT activity to insulin. The findings suggest that insulin plays a role in mediating cholinergic differentiation in the embryonic chicken retina

Acidification counteracts negative effects of warming on diatom silicification

KAUST Repository

Coello-Camba, Alexandra; Agusti, Susana

2016-01-01

Diatoms are a significant group contributing up to 40 % of annual primary production in the oceans. They have a special siliceous cell wall that, acting as a ballast, plays a key role in the sequestration of global carbon and silica. Diatoms dominate primary production in the Arctic Ocean, where global climate change is causing increases in water temperature and in the partial pressure of CO2 (pCO2). Here we show that as water temperature increases diatoms become stressed, grow to smaller sizes, and decrease their silicification rates. But at higher pCO2, as the pH of seawater decreases, silica incorporation rates are increased. In a future warmer Arctic ocean diatoms may have a competitive advantage under increased ocean acidification, as increased pCO2 counteracts the adverse effects of increasing temperature on silicification and buffers its consequences in the biogeochemical cycles of carbon and silica.

Acidification counteracts negative effects of warming on diatom silicification

KAUST Repository

Coello-Camba, Alexandra

2016-10-24

Diatoms are a significant group contributing up to 40 % of annual primary production in the oceans. They have a special siliceous cell wall that, acting as a ballast, plays a key role in the sequestration of global carbon and silica. Diatoms dominate primary production in the Arctic Ocean, where global climate change is causing increases in water temperature and in the partial pressure of CO2 (pCO2). Here we show that as water temperature increases diatoms become stressed, grow to smaller sizes, and decrease their silicification rates. But at higher pCO2, as the pH of seawater decreases, silica incorporation rates are increased. In a future warmer Arctic ocean diatoms may have a competitive advantage under increased ocean acidification, as increased pCO2 counteracts the adverse effects of increasing temperature on silicification and buffers its consequences in the biogeochemical cycles of carbon and silica.

Counteraction of urea-induced protein denaturation by trimethylamine N-oxide: a chemical chaperone at atomic resolution.

Science.gov (United States)

Bennion, Brian J; Daggett, Valerie

2004-04-27

Proteins are very sensitive to their solvent environments. Urea is a common chemical denaturant of proteins, yet some animals contain high concentrations of urea. These animals have evolved an interesting mechanism to counteract the effects of urea by using trimethylamine N-oxide (TMAO). The molecular basis for the ability of TMAO to act as a chemical chaperone remains unknown. Here, we describe molecular dynamics simulations of a small globular protein, chymotrypsin inhibitor 2, in 8 M urea and 4 M TMAO/8 M urea solutions, in addition to other control simulations, to investigate this effect at the atomic level. In 8 M urea, the protein unfolds, and urea acts in both a direct and indirect manner to achieve this effect. In contrast, introduction of 4 M TMAO counteracts the effect of urea and the protein remains well structured. TMAO makes few direct interactions with the protein. Instead, it prevents unfolding of the protein by structuring the solvent. In particular, TMAO orders the solvent and discourages it from competing with intraprotein H bonds and breaking up the hydrophobic core of the protein.

Identificación y caracterización de la población total de las células ganglionares de la retina en rata : nuevos métodos de trazado, expresión de melanopsina y de factores de transcripción Brn3:estudio de la respuesta neuronal y microglial a la axotomía y efecto del envejecimiento en la retina

OpenAIRE

Nadal Nicolás, Francisco Manuel

2015-01-01

Introducción La retina es parte del sistema nervioso central (SNC) y se localiza en la cara interna del globo ocular. Su función principal es la fototransducción de las ondas electromagnéticas del espectro de la luz visible en energía eléctrica. Esta función es realizada por los fotorreceptores (conos y bastones). Tras su procesamiento, la información llega a las células ganglionares de retina (CGR). Las CGR son las únicas neuronas aferentes de la retina y transmiten la información visual ...

Testing the biocompatibility of a glutathione-containing intra-ocular irrigation solution by using an isolated perfused bovine retina organ culture model - an alternative to animal testing.

Science.gov (United States)

Januschowski, Kai; Zhour, Ahmad; Lee, Albert; Maddani, Ramin; Mueller, Sebastien; Spitzer, Martin S; Schnichels, Sven; Schultheiss, Maximilian; Doycheva, Deshka; Bartz-Schmidt, Karl-Ulrich; Szurman, Peter

2012-03-01

The effects of a glutathione-containing intra-ocular irrigation solution, BSS Plus©, on retinal function and on the survival of ganglion cells in whole-mount retinal explants were studied. Evidence is provided that the perfused ex vivo bovine retina can serve as an alternative to in vivo animal testing. Isolated bovine retinas were prepared and perfused with an oxygen-saturated standard irrigation solution, and an electroretinogram was recorded to assess retinal function. After stable b-waves were detected, the isolated retinas were perfused with BSS Plus for 45 minutes. To investigate the effects of BSS Plus on photoreceptor function, 1mM aspartate was added to the irrigation solution in order to obtain a-waves, and the ERG trace was monitored for 75 minutes. For histological analysis, isolated whole retinal mounts were stored for 24 hours at 4°C, in the dark. The percentages of cell death in the retinal ganglion cell layer and in the outer and inner nuclear layers were estimated by using an ethidium homodimer-1 stain and the TUNEL assay. General swelling of the retina was examined with high-resolution optical coherence tomography. During perfusion with BSS Plus, no significant changes in a-wave and b-wave amplitudes were recorded. Retinas stored for 24 hours in BSS Plus showed a statistically significant smaller percentage (52.6%, standard deviation [SD] = 16.1%) of cell death in the retinal ganglion cell layer compared to the control group (69.6%, SD = 3.9, p = 0.0031). BSS Plus did not seem to affect short-term retinal function, and had a beneficial effect on the survival of retinal ganglion cells. This method for analysing the isolated perfused retina represents a valuable alternative for testing substances for their retinal biocompatibility and toxicity. 2012 FRAME.

Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

International Nuclear Information System (INIS)

Kim, Yeoun-Hee; Chang, Yongmin; Jung, Jae-Chang

2012-01-01

Highlights: ► Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. ► Staurosporine mediates uPA activation during RGC differentiation in vitro. ► Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. ► Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that uPA plays a role in the staurosporine-mediated stimulation of RGC differentiation.

Pharmacological differences between the D-2 autoreceptor and the D-1 dopamine receptor in rabbit retina

International Nuclear Information System (INIS)

Dubocovich, M.L.; Weiner, N.

1985-01-01

The effect of dopamine receptor agonists and antagonists was studied on the calcium-dependent release of [ 3 H]dopamine elicited by field stimulation at 3 Hz for a duration of 1 min (20 mA, 2 msec) from the rabbit retina in vitro and on adenylate cyclase activity in homogenates of rabbit retina. The relative order of potency of dopamine receptor agonists to inhibit the stimulation-evoked [ 3 H]dopamine release was pergolide greater than bromocriptine greater than apomorphine greater than LY 141865 greater than N,N-di-n-propyldopamine greater than or equal to dopamine. The relative order of potencies of dopamine receptor antagonists to increase [ 3 H]dopamine release was: S-sulpiride greater than or equal to domperidone greater than or equal to spiroperidol greater than metoclopramide greater than fluphenazine greater than or equal to R-sulpiride. alpha-Flupenthixol (0.01-1 microM) and (+)-butaclamol (0.01-1 microM) did not increase [ 3 H]dopamine overflow when added alone, but they antagonized the concentration-dependent inhibitory effect of apomorphine (0.1-10 microM). These results suggest that the dopamine inhibitory autoreceptor involved in the modulation of dopamine release from the rabbit retina possesses the pharmacological characteristics of a D-2 dopamine receptor. Maximal stimulation by 30 microM dopamine resulted in a 3-fold increase in adenylate cyclase activity with half-maximal stimulation occurring at a concentration of 2.46 microM. Apomorphine and pergolide elicited a partial stimulation of adenylate cyclase activity. However, at low concentrations both compounds were more potent than dopamine

Lack of the sodium-driven chloride bicarbonate exchanger NCBE impairs visual function in the mouse retina.

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Gerrit Hilgen

Full Text Available Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10, a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pH(i and chloride concentration ([Cl(-](i in neurons. Here we show that NCBE is strongly expressed in the retina. As GABA(A receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina. Importantly, we found a differential expression of NCBE in bipolar cells: whereas NCBE was expressed on ON and OFF bipolar cell axon terminals, it only localized to dendrites of OFF bipolar cells. On these compartments, NCBE colocalized with the main neuronal chloride extruder KCC2, which renders GABA hyperpolarizing. NCBE was also expressed in starburst amacrine cells, but was absent from neurons known to depolarize in response to GABA, like horizontal cells. Mice lacking NCBE showed decreased visual acuity and contrast sensitivity in behavioral experiments and smaller b-wave amplitudes and longer latencies in electroretinograms. Ganglion cells from NCBE-deficient mice also showed altered temporal response properties. In summary, our data suggest that NCBE may serve to maintain intracellular chloride and bicarbonate concentration in retinal neurons. Consequently, lack of NCBE in the retina may result in changes in pH(i regulation and chloride-dependent inhibition, leading to altered signal transmission and impaired visual function.

Maintenance of lettuce seed viability and counter-action of radiation damage by moisture equilibration-drying treatment

International Nuclear Information System (INIS)

Punjabi, Bina; Basu, R.N.

1982-01-01

Lettuce seeds were subjected to X- and gamma-radiation after moisture equilibration-drying or they were equilibrated with a saturated atmosphere for 24 hrs immediately after irradiation followed by drying back to the original weight. Results showed that moisture-equilibration drying treatment either before or after irradiation counteracts the adverse effects of irradiation. (M.G.B.)

Maintenance of lettuce seed viability and counter-action of radiation damage by moisture equilibration-drying treatment

Energy Technology Data Exchange (ETDEWEB)

Punjabi, B; Basu, R N

1982-10-01

Lettuce seeds were subjected to X- and gamma-radiation after moisture equilibration-drying or they were equilibrated with a saturated atmosphere for 24 hrs immediately after irradiation followed by drying back to the original weight. Results showed that moisture-equilibration drying treatment either before or after irradiation counteracts the adverse effects of irradiation. (M.G.B.). 14 refs.

Can we grow new retina?

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Geeta K Vemuganti

2006-03-01

Full Text Available Introduction Retinal degenerations and dystrophies, the major causes of genetically inherited blindness, are characterised by the death or degeneration of photoreceptors (rods and/or cones.1 Approaches to treating this disease include: a replacing the defective gene; b introducing a drug or agent that either slows down or stops the premature death of photoreceptors; c introducing electronic chips; or d replacing the damaged cells by cellular therapy. Gene therapy is aimed at counteracting the defective gene by substituting it with the normal gene in the target tissues. Though successful visual recovery has been reported with gene therapy in dog models,2-3 it remains a challenge to identify a safe and reliable way of introducing the corrective gene in humans, given that the genes need to act for the lifetime of the patient. Introduction of ‘a’ factors (such as growth factors into the eye, directly or through implants, is another novel approach to preventing or slowing premature cell death.4-5 The challenge lies in delivering the drug to the appropriate site in a safe and sustained manner. Electronic chips, similar to the ones used for audio aids, have shown exciting results in some studies, but the technology is still in its infancy.6-7

In Silico Ocular Pharmacokinetic Modeling: Delivery of Topical FK962 to Retina.

Science.gov (United States)

Mori, Ayumi; Yabuta, Chiho; Kishimoto, Yayoi; Kozai, Seiko; Ohtori, Akira; Shearer, Thomas R; Azuma, Mitsuyoshi

2017-09-01

To establish the in silico ocular pharmacokinetic modeling for eye drops, and to simulate the dose regimen for FK962 in human choroid/retinal diseases. Pharmacokinetics for FK962 in vivo was performed by a single instillation of drops containing 0.1% 14 C-FK962 in rabbit eyes. Permeation of FK962 across the cornea, sclera, and choroid/retina was measured in vitro. Neurite elongation by FK962 was measured in cultured rat retinal ganglion cells. Parameters from the experimental data were used in an improved in silico model of ocular pharmacokinetics of FK962 in man. The mean concentration of FK962 in ocular tissues predicted by in silico modeling was consistent with in vivo results, validating the in silico model. FK962 rapidly penetrated into the anterior and posterior segments of the eye and then diffused into the vitreous body. The in silico pharmacokinetic modeling also predicted that a dose regimen of 0.0054% FK962 twice per day would produce biologically effective concentrations of FK962 in the choroid/retina, where FK962 facilitates rat neurite elongation. Our in silico model for ocular pharmacokinetics is useful (1) for predicting drug concentrations in specific ocular tissues after topical instillation, and (2) for suggesting the optimal dose regimens for eye drops. The pharmacodynamics for FK962 produced by this model may be useful for clinical trials against retinal neuropathy.

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

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Asuka Baba

2015-01-01

Full Text Available Backgroud/Aims: Besides its anti-allergic properties as a histamine receptor antagonist, olopatadine stabilizes mast cells by inhibiting the release of chemokines. Since olopatadine bears amphiphilic features and is preferentially partitioned into the lipid bilayers of the plasma membrane, it would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of olopatadine and other anti-allergic drugs on the membrane capacitance (Cm in rat peritoneal mast cells during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Low concentrations of olopatadine (1 or 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, 100 µM and 1 mM olopatadine almost totally suppressed the increase in the Cm. Additionally, these doses completely washed out the trapping of the dye on the cell surface, indicating that olopatadine counteracted the membrane surface deformation induced by exocytosis. As shown by electron microscopy, olopatadine generated inward membrane bending in mast cells. Conclusion: This study provides electrophysiological evidence for the first time that olopatadine dose-dependently inhibits the process of exocytosis in rat peritoneal mast cells. Such mast cell stabilizing properties of olopatadine may be attributed to its counteracting effects on the plasma membrane deformation in degranulating mast cells.

Measuring mouse retina response near the detection threshold to direct stimulation of photons with sub-poisson statistics

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Tavala, Amir; Dovzhik, Krishna; Schicker, Klaus; Koschak, Alexandra; Zeilinger, Anton

Probing the visual system of human and animals at very low photon rate regime has recently attracted the quantum optics community. In an experiment on the isolated photoreceptor cells of Xenopus, the cell output signal was measured while stimulating it by pulses with sub-poisson distributed photons. The results showed single photon detection efficiency of 29 +/-4.7% [1]. Another behavioral experiment on human suggests a less detection capability at perception level with the chance of 0.516 +/-0.01 (i.e. slightly better than random guess) [2]. Although the species are different, both biological models and experimental observations with classical light stimuli expect that a fraction of single photon responses is filtered somewhere within the retina network and/or during the neural processes in the brain. In this ongoing experiment, we look for a quantitative answer to this question by measuring the output signals of the last neural layer of WT mouse retina using microelectrode arrays. We use a heralded downconversion single-photon source. We stimulate the retina directly since the eye lens (responsible for 20-50% of optical loss and scattering [2]) is being removed. Here, we demonstrate our first results that confirms the response to the sub-poisson distributied pulses. This project was supported by Austrian Academy of Sciences, SFB FoQuS F 4007-N23 funded by FWF and ERC QIT4QAD 227844 funded by EU Commission.

Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina.

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Meguro, Akira; Ideta, Hidenao; Ota, Masao; Ito, Norihiko; Ideta, Ryuichi; Yonemoto, Junichi; Takeuchi, Masaki; Uemoto, Riyo; Nishide, Tadayuki; Iijima, Yasuhito; Kawagoe, Tatsukata; Okada, Eiichi; Shiota, Tomoko; Hagihara, Yuta; Oka, Akira; Inoko, Hidetoshi; Mizuki, Nobuhisa

2012-01-01

Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls) led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4) gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls) using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8 × 10(-6), OR = 0.63 and Pc = 1.0 × 10(-5), OR = 0.69 in a total of 574 patients and 608 controls, respectively). Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.

Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina.

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Akira Meguro

Full Text Available Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4 gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8 × 10(-6, OR = 0.63 and Pc = 1.0 × 10(-5, OR = 0.69 in a total of 574 patients and 608 controls, respectively. Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.

Exposure to nature counteracts aggression after depletion.

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Wang, Yan; She, Yihan; Colarelli, Stephen M; Fang, Yuan; Meng, Hui; Chen, Qiuju; Zhang, Xin; Zhu, Hongwei

2018-01-01

Acts of self-control are more likely to fail after previous exertion of self-control, known as the ego depletion effect. Research has shown that depleted participants behave more aggressively than non-depleted participants, especially after being provoked. Although exposure to nature (e.g., a walk in the park) has been predicted to replenish resources common to executive functioning and self-control, the extent to which exposure to nature may counteract the depletion effect on aggression has yet to be determined. The present study investigated the effects of exposure to nature on aggression following depletion. Aggression was measured by the intensity of noise blasts participants delivered to an ostensible opponent in a competition reaction-time task. As predicted, an interaction occurred between depletion and environmental manipulations for provoked aggression. Specifically, depleted participants behaved more aggressively in response to provocation than non-depleted participants in the urban condition. However, provoked aggression did not differ between depleted and non-depleted participants in the natural condition. Moreover, within the depletion condition, participants in the natural condition had lower levels of provoked aggression than participants in the urban condition. This study suggests that a brief period of nature exposure may restore self-control and help depleted people regain control over aggressive urges. © 2017 Wiley Periodicals, Inc.

PBN (Phenyl-N-Tert-Butylnitrone-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage.

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Megan Stiles

Full Text Available A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD, and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control. In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat

PBN (Phenyl-N-Tert-Butylnitrone)-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage.

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Stiles, Megan; Moiseyev, Gennadiy P; Budda, Madeline L; Linens, Annette; Brush, Richard S; Qi, Hui; White, Gary L; Wolf, Roman F; Ma, Jian-Xing; Floyd, Robert; Anderson, Robert E; Mandal, Nawajes A

2015-01-01

A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from

Vitreous in lattice degeneration of retina.

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Foos, R Y; Simons, K B

1984-05-01

A localized pocket of missing vitreous invariably overlies lattice degeneration of the retina. Subjects with lattice also have a higher rate of rhegmatogenous retinal detachment, which is usually a complication of retinal tears. The latter are in turn a result of alterations in the central vitreous--that is, synchysis senilis leading to posterior vitreous detachment. In order to determine if there is either an association or a deleterious interaction between the local and central lesions of the vitreous in eyes with lattice, a comparison was made in autopsy eyes with and without lattice the degree of synchysis and rate of vitreous detachment. Results show no association between the local and central vitreous lesions, indicating that a higher rate of vitreous detachment is not the basis for the higher rate of retinal detachment in eyes with lattice. Also, there was no suggestion of deleterious interaction between the local and central vitreous lesions, either through vitreodonesis as a basis for precocious vitreous detachment, or through a greater degree of synchysis as a basis for interconnection of local and central lacunae (which could extend the localized retinal detachment in eyes with holes in lattice degeneration).

Tumor vasoproliferativo de retina.: Reporte de dos casos Vasoproliferative retinal tumor.: Report of two cases

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Danaides Arencibia González

2010-12-01

Full Text Available El tumor vasoproliferativo de retina es una condición rara y benigna que presenta una lesión exudativa de retina periférica. La lesión puede ser clasificada en primaria (idiopática o secundaria a otros procesos oculares. Las opciones terapéuticas incluyen observación, crioablación tisular, fotocoagulación láser, remoción quirúrgica mediante vitrectomía, terapia fotodinámica y braquiterapia epiescleral con isótopos radioactivos, asociadas o no al uso de antiangiogénicos o antiinflamatorios, siendo la elección de la modalidad de manejo particular en cada caso. Presentamos dos casos en pacientes femeninas portadoras de esta condición de los que describimos las características más importantes del cuadro clínico, retinografías, angiografía fluoresceínica y ecografía, así como el manejo y curso evolutivo-terapéutico.Vasoproliferative retinal tumor is a rare and benign condition that presents as an exudative lesion in the peripheral retina. The lesion can be classified in primary (idiopathic or secondary to other ocular processes. Therapeutic options include observation, cryotherapy, laser photocoagulation, surgical removal by pars plana vitrectomy, photodynamic therapy and epiescleral brachytheraphy with radio-active isotopes associated or not to the use of anti-angiogenic or anti-inflammatory drugs. The selection of a particular management modality depends on the type of case. Two female patients affected with this condition were presented; the most important characteristics in their clinical pictures, as well as the results of other tests as retinography, fluorescent and ICG angiography and echography were described. The management and the therapeutical and evolutive course of both patients were also discussed.

Distribution of mammalian-like melanopsin in cyclostome retinas exhibiting a different extent of visual functions.

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Lanfang Sun

Full Text Available Mammals contain 1 melanopsin (Opn4 gene that is expressed in a subset of retinal ganglion cells to serve as a photopigment involved in non-image-forming vision such as photoentrainment of circadian rhythms. In contrast, most nonmammalian vertebrates possess multiple melanopsins that are distributed in various types of retinal cells; however, their functions remain unclear. We previously found that the lamprey has only 1 type of mammalian-like melanopsin gene, which is similar to that observed in mammals. Here we investigated the molecular properties and localization of melanopsin in the lamprey and other cyclostome hagfish retinas, which contribute to visual functions including image-forming vision and mainly to non-image-forming vision, respectively. We isolated 1 type of mammalian-like melanopsin cDNA from the eyes of each species. We showed that the recombinant lamprey melanopsin was a blue light-sensitive pigment and that both the lamprey and hagfish melanopsins caused light-dependent increases in calcium ion concentration in cultured cells in a manner that was similar to that observed for mammalian melanopsins. We observed that melanopsin was distributed in several types of retinal cells, including horizontal cells and ganglion cells, in the lamprey retina, despite the existence of only 1 melanopsin gene in the lamprey. In contrast, melanopsin was almost specifically distributed to retinal ganglion cells in the hagfish retina. Furthermore, we found that the melanopsin-expressing horizontal cells connected to the rhodopsin-containing short photoreceptor cells in the lamprey. Taken together, our findings suggest that in cyclostomes, the global distribution of melanopsin in retinal cells might not be related to the melanopsin gene number but to the extent of retinal contribution to visual function.

Simple explant culture of the embryonic chicken retina with long-term preservation of photoreceptors.

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Thangaraj, Gopenath; Greif, Alexander; Layer, Paul G

2011-10-01

Structurally stable in vitro-model systems are indispensible to analyse neural development during embryogenesis, follow cellular differentiation and evaluate neurotoxicological or growth factor effects. Here we describe a three-dimensional, long-term in vitro-culture system of the embryonic chick retina which supports photoreceptor development. Retinal tissue was isolated from E6 chick eye, and cultured as explants by continuous orbital rotation to allow free floatation without any supporting materials. Young stage (E6) immature retinas were cultured for various time periods in order to follow the differentiation of cell types and plexiform layers by immunocytochemical methods. These explants could be cultured for at least 2-3 weeks with remarkable retention of retinal architecture. Interestingly, photoreceptors developed in the absence of pigment epithelium. Electron microscopic studies revealed formation of structures resembling photoreceptor outer segments, a feature not reported previously. Thus, the verification of photoreceptors, Müller cells, inner retinal cells and the inner plexiform layer described in our study establishes this explant culture as a valuable in vivo-like model system. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Analgesia preemptiva com dipirona versus ibuprofeno na fotocoagulação a laser da retina

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Artur Macaferri Del Santo

2016-02-01

Full Text Available RESUMO Objetivo: Comparar a efetividade da dipirona versus o ibuprofeno para a redução da dor na fotocoagulação da retina (FR. Método: Foi realizado um estudo controlado, duplo cego e randomizado englobando trinta e quatro pacientes com retinopatia diabética separados em dois grupos. Grupo A recebeu 1000mg de dipirona e o grupo B recebeu 600mg de ibuprofeno. A dor foi avaliada pela escala visual analógica. Resultado: A média do escore da dor nos grupos A e B foi de 5,2 ± 2.6 e 4,5 ± 1,4, respectivamente. Não houve diferença estatística entre os grupos (p=0,34. O mesmo foi observado quanto à analise entre dor leve, moderada e grave (p=0,09. Os grupos foram semelhantes quanto à idade e sexo. Conclusão: Os medicamentos foram equivalentes ou equipotentes em reduzir a dor ocular durante a fotocoagulação a laser da retina.

Efficiency of RAFT-synthesized PDMAEMA in gene transfer to the retina.

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Bitoque, Diogo B; Simão, Sónia; Oliveira, Ana V; Machado, Susana; Duran, Margarita R; Lopes, Eduardo; da Costa, Ana M Rosa; Silva, Gabriela A

2017-01-01

Gene therapy has long been heralded as the new hope to evolve from symptomatic care of genetic pathologies to a full cure. Recent successes in using gene therapy for treating several ocular and haematopoietic pathologies have shown the great potential of this approach that, in the early days, relied on the use of viral vectors, which were considered by many to be undesirable for human treatment. Therefore, there is considerable interest and effort in developing non-viral vectors, with efficiency close to that of viral vectors. The aim of this study was to develop suitable non-viral carriers for gene therapy to treat pathologies affecting the retina. In this study poly(2-(N,N-dimethylamino)ethyl methacrylate), PDMAEMA was synthesized by reversible addition-fragmentation chain transfer (RAFT) and the in vitro cytocompatibility and transfection efficiency of a range of polymer:DNA ratios evaluated using a retinal cell line; in vivo biocompatibility was evaluated by ocular injection in C57BL/6 mice. The results showed that through RAFT, it is possible to produce a defined-size polymer that is compatible with cell viability in vitro and capable of efficiently directing gene expression in a polymer-DNA ratio-dependent manner. When injected into the eyes of mice, these vectors induced a transient, mild inflammation, characteristic of the implantation of medical devices. These results form the basis of future studies where RAFT-synthesized PDMAEMA will be used to deliver gene expression systems to the retina of mouse models of retinal pathologies. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Toward automated selective retina treatment (SRT): an optical microbubble detection technique

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Seifert, Eric; Park, Young-Gun; Theisen-Kunde, Dirk; Roh, Young-Jung; Brinkmann, Ralf

2018-02-01

Selective retina therapy (SRT) is an ophthalmological laser technique, targeting the retinal pigment epithelium (RPE) with repetitive microsecond laser pulses, while causing no thermal damage to the neural retina, the photoreceptors as well as the choroid. The RPE cells get damaged mechanically by microbubbles originating, at the intracellular melanosomes. Beneficial effects of SRT on Central Serous Retinopathy (CSR) and Diabetic Macula Edema (DME) have already been shown. Variations in the transmission of the anterior eye media and pigmentation variation of RPE yield in intra- and inter- individual thresholds of the pulse energy required for selective RPE damage. Those selective RPE lesions are not visible. Thus, dosimetry-systems, designed to detect microbubbles as an indicator for RPE cell damage, are demanded elements to facilitate SRT application. Therefore, a technique based on the evaluation of backscattered treatment light has been developed. Data of 127 spots, acquired during 10 clinical treatments of CSR patients, were assigned to a RPE cell damage class, validated by fluorescence angiography (FLA). An algorithm has been designed to match the FLA based information. A sensitivity of 0.9 with a specificity close to 1 is achieved. The data can be processed within microseconds. Thus, the process can be implemented in existing SRT lasers with an automatic pulse wise increasing energy and an automatic irradiation ceasing ability to enable automated treatment close above threshold to prevent adverse effects caused by too high pulse energy. Alternatively, a guidance procedure, informing the treating clinician about the adequacy of the actual settings, is possible.

Pushing the limits of photoreception in twilight conditions: The rod-like cone retina of the deep-sea pearlsides

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Busserolles, Fanny de; Cortesi, Fabio; Helvik, Jon Vidar; Davies, Wayne I. L.; Templin, Rachel M.; Sullivan, Robert K. P.; Michell, Craig T.; Mountford, Jessica K.; Collin, Shaun P.; Irigoien, Xabier; Kaartvedt, Stein; Marshall, Justin

2017-01-01

retina does not have rod photoreceptors only; instead, it is composed almost exclusively of transmuted cone photoreceptors. These transmuted cells combine the morphological characteristics of a rod photoreceptor with a cone opsin and a cone

Acidosis counteracts itch tachyphylaxis to consecutive pruritogen exposure dependent on acid-sensing ion channel 3.

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Jiang, Yi-Ming; Huang, Chen; Peng, Zhong; Han, Shao-Ling; Li, Wei-Guang; Zhu, Michael Xi; Xu, Tian-Le

2017-01-01

Tachyphylaxis of itch refers to a markedly reduced scratching response to consecutive exposures of a pruritogen, a process thought to protect against tissue damage by incessant scratching and to become disrupted in chronic itch. Here, we report that a strong stimulation of the Mas-related G-protein-coupled receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH 2 (SL-NH 2 ) or bovine adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces tachyphylaxis to the subsequent application of SL-NH 2 to the same site. Notably, co-application of acid and SL-NH 2 following the initial injection of the pruritogen alone counteracted itch tachyphylaxis by augmenting the scratching behaviors in wild-type but not in acid-sensing ion channel 3-null, animals. Using an activity-dependent silencing strategy, we identified that acid-sensing ion channel 3-mediated itch enhancement mainly occurred via the Mas-related G-protein-coupled receptor C11-responsive sensory neurons. Together, our results indicate that acid-sensing ion channel 3, activated by concomitant acid and certain pruritogens, constitute a novel signaling pathway that counteracts itch tachyphylaxis to successive pruritogenic stimulation, which likely contributes to chronic itch associated with tissue acidosis.

Rod and cone interactions in the retina [version 1; referees: 4 approved

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Gordon Fain

2018-05-01

Full Text Available We have long known that rod and cone signals interact within the retina and can even contribute to color vision, but the extent of these influences has remained unclear. New results with more powerful methods of RNA expression profiling, specific cell labeling, and single-cell recording have provided greater clarity and are showing that rod and cone signals can mix at virtually every level of signal processing. These interactions influence the integration of retinal signals and make an important contribution to visual perception.

An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA.

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Guo-Xiang Ruan

2008-10-01

Full Text Available The influence of the mammalian retinal circadian clock on retinal physiology and function is widely recognized, yet the cellular elements and neural regulation of retinal circadian pacemaking remain unclear due to the challenge of long-term culture of adult mammalian retina and the lack of an ideal experimental measure of the retinal circadian clock. In the current study, we developed a protocol for long-term culture of intact mouse retinas, which allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC clock gene reporter. With this in vitro assay, we studied the characteristics and location within the retina of circadian PER2::LUC rhythms, the influence of major retinal neurotransmitters, and the resetting of the retinal circadian clock by light. Retinal PER2::LUC rhythms were routinely measured from whole-mount retinal explants for 10 d and for up to 30 d. Imaging of vertical retinal slices demonstrated that the rhythmic luminescence signals were concentrated in the inner nuclear layer. Interruption of cell communication via the major neurotransmitter systems of photoreceptors and ganglion cells (melatonin and glutamate and the inner nuclear layer (dopamine, acetylcholine, GABA, glycine, and glutamate did not disrupt generation of retinal circadian PER2::LUC rhythms, nor did interruption of intercellular communication through sodium-dependent action potentials or connexin 36 (cx36-containing gap junctions, indicating that PER2::LUC rhythms generation in the inner nuclear layer is likely cell autonomous. However, dopamine, acting through D1 receptors, and GABA, acting through membrane hyperpolarization and casein kinase, set the phase and amplitude of retinal PER2::LUC rhythms, respectively. Light pulses reset the phase of the in vitro retinal oscillator and dopamine D1 receptor antagonists attenuated these phase shifts. Thus, dopamine and GABA act at the molecular level of PER

Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

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Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

2012-01-01

In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance between excitation and inhibition in the outer retina needs to be adaptable. How this is achieved is unknown. Using electrophysiological techniques in the isolated retina of the goldfish, it was found that opening Ca2+-dependent Cl− channels in recorded cones reduced the size of feedback responses measured in both cones and HCs. Furthermore, we show that cones express Cl− channels that are gated by GABA released from HCs. Similar to activation of ICl(Ca), opening of these GABA-gated Cl− channels reduced the size of light-induced feedback responses both in cones and HCs. Conversely, application of picrotoxin, a blocker of GABAA and GABAC receptors, had the opposite effect. In addition, reducing GABA release from HCs by blocking GABA transporters also led to an increase in the size of feedback. Because the independent manipulation of Ca2+-dependent Cl− currents in individual cones yielded results comparable to bath-applied GABA, it was concluded that activation of either Cl− current by itself is sufficient to reduce the size of HC feedback. However, additional effects of GABA on outer retinal processing cannot be excluded. These results can be accounted for by an ephaptic feedback model in which a cone Cl− current shunts the current flow in the synaptic cleft. The Ca2+-dependent Cl− current might be essential to set the initial balance between the feedforward and the feedback signals active in the cone HC synapse. It prevents that strong feedback from HCs to cones flood the cone with Ca2+. Modulation of the feedback strength by GABA might play a role during light/dark adaptation, adjusting the amount of negative feedback to the signal to noise ratio of the

Neural retina-specific Aldh1a1 controls dorsal choroidal vascular development via Sox9 expression in retinal pigment epithelial cells.

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Goto, So; Onishi, Akishi; Misaki, Kazuyo; Yonemura, Shigenobu; Sugita, Sunao; Ito, Hiromi; Ohigashi, Yoko; Ema, Masatsugu; Sakaguchi, Hirokazu; Nishida, Kohji; Takahashi, Masayo

2018-04-03

VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that Aldh1a1 -/- mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in Aldh1a1 -/- mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells. An RA-deficient diet resulted in dorsal choroidal hypoplasia, and simple RA treatment of Aldh1a1 -/- pregnant females suppressed choroid hypoplasia in their offspring. We also found downregulation of Sox9 in the dorsal neural retina and RPE of Aldh1a1 -/- mice and RPE-specific disruption of Sox9 phenocopied Aldh1a1 -/- choroidal development. These results suggest that RAs produced by Aldh1a1 in the neural retina directs dorsal choroidal vascular development via Sox9 upregulation in the dorsal RPE cells to enhance RPE-derived VEGF secretion. © 2018, Goto et al.

Wavefront optimized nonlinear microscopy of ex vivo human retinas

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Gualda, Emilio J.; Bueno, Juan M.; Artal, Pablo

2010-03-01

A multiphoton microscope incorporating a Hartmann-Shack (HS) wavefront sensor to control the ultrafast laser beam's wavefront aberrations has been developed. This instrument allowed us to investigate the impact of the laser beam aberrations on two-photon autofluorescence imaging of human retinal tissues. We demonstrated that nonlinear microscopy images are improved when laser beam aberrations are minimized by realigning the laser system cavity while wavefront controlling. Nonlinear signals from several human retinal anatomical features have been detected for the first time, without the need of fixation or staining procedures. Beyond the improved image quality, this approach reduces the required excitation power levels, minimizing the side effects of phototoxicity within the imaged sample. In particular, this may be important to study the physiology and function of the healthy and diseased retina.

Color opponency in cone-driven horizontal cells in carp retina. Aspecific pathways between cones and horizontal cells

NARCIS (Netherlands)

Kamermans, M.; van Dijk, B. W.; Spekreijse, H.

1991-01-01

The spectral and dynamic properties of cone-driven horizontal cells in carp retina were evaluated with silent substitution stimuli and/or saturating background illumination. The aim of this study was to describe the wiring underlying the spectral sensitivity of these cells. We will present

La tomografía de coherencia óptica en el diagnóstico de enfermedades de la retina y el nervio óptico Optic coherence tomography in the diagnosis of the retina and optic nerve diseases

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Carlos E Mendoza Santiesteban

2005-12-01

Full Text Available El autor principal hace una exposición sobre los principales métodos imagenológicos en la oftalmología y sus fundamentos, en especial de la tomografía óptica coherente con el equipo Stratus 3000. Con su colectivo de autores presenta una galería de imágenes de la tomografía óptica coherente acompañadas de imágenes de fondo de ojo y los campos visuales, de más de 500 pacientes con diversas enfermedades de retina y nervio óptico, lo que constituye el primer atlas cubano sobre esta entidadThe main author exposes the main imaging methods used in ophthalmology and their foundations, specially the optic coherence tomography with the Stratus 3000 equipment. Together with the other authors, he presents a gallery of images of the optic coherence tomography accompanied with images of the fundus oculi and the visual fields of more than 500 patients with different diseases of the retina and optic nerve, which constitute the first Cuban athlas on this entity

Coronavirus gene 7 counteracts host defenses and modulates virus virulence.

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Jazmina L G Cruz

2011-06-01

Full Text Available Transmissible gastroenteritis virus (TGEV genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7. Both the mutant and the parental (rTGEV-wt viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c, a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the

Hereditary retinal eye diseases in childhood and youth affecting the central retina

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Martin M Nentwich

2013-01-01

Classic examinations for patients suffering from hereditary retinal dystrophies of the central retina are funduscopy - also using red-free light - visual-field tests, electrophysiologic tests as electro-retinogram [ERG] and multifocal ERG and tests evaluating color vision. Recently, new imaging modalities have been introduced into the clinical practice. The significance of these new methods such as high-resolution spectral-domain optic coherence tomography [SD-OCT] and fundus autofluorescence will be discussed as well as "next generation sequencing" as a new method for the analysis of genetic mutations in a larger number of patients.

Pathological changes in the retina of eyes rats with experimental 2 type diabetes mellitus and their correction by oral gels with biologically active substances

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V. V. Vit

2014-07-01

Full Text Available Purpose: To study of therapeutic and prophylactic action on the retina of rats with experimental diabetes mellitus type 2 (DM2 oral mucosal gels containing biologically active substances (BAS.Methods: DM2 was induced by protamine method Ulyanov and Tarasova [2000]. As BAS used lysozyme, flour of grape leaves, the water extract of blueberries and quercetin. Mucosal gels containing active substances, applied to the mucous lining of the mouth for 2 weeks. The serum glucose concentration was performed and histological studies of the retina.Results: Application mucosal gels reduces BAS 8‑22 % glucose (most with blueberry extract and significantly improves retinal histology (vacuolar degeneration less pronounced ganglion cells, there are no structural changes in photoreceptor layer. Gels revealed more effective with containing extract of bilberry, grape flour and quercetin.Conclusion: Oral mucosal application of gels containing active substances, have protection of retina in diabetes mellitus type 2.

Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

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Maria Giovanna Scioli

Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

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Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

2013-12-01

Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. �

Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

International Nuclear Information System (INIS)

Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

2013-01-01

Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. �

Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway.

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Hong Pan

Full Text Available Retinal ischemia-reperfusion (I/R injury induces oxidative stress, leukocyte infiltration, and neuronal cell death. Sulforaphane (SF, which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. These effects can be initiated through nuclear factor E2-related factor 2 (Nrf2-mediated induction of heme oxygenase-1 (HO-1. This investigation was designed to elucidate the neural protective mechanisms of SF in the retinal I/R rat model. Animals were intraperitoneally (i.p. injected with SF (12.5 mg/kg or vehicle (corn oil once a day for 7 consecutive days. Then, retinal I/R was made by elevating the intraocular pressure (IOP to 130 mmHg for 1 h. To determine if HO-1 was involved in the Nrf2 antioxidant pathway, rats were subjected to protoporphyrin IX zinc (II (ZnPP, 30 mg/kg, i.p. treatments at 24 h before retinal ischemia. The neuroprotective effects of SF were assessed by determining the morphology of the retina, counting the infiltrating inflammatory cells and the surviving retinal ganglion cells (RGCs and amacrine cells, and measuring apoptosis in the retinal layers. The expression of Nrf2 and HO-1 was studied by immunofluorescence analysis and western blotting. I/R induced a marked increase of ROS generation, caused pronounced inflammation, increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer (IRL, and these effects were diminished or abolished by SF pretreatment. Meanwhile, SF pretreatment significantly elevated the nuclear accumulation of Nrf2 and the level of HO-1 expression in the I/R retinas; however, ZnPP reversed the protective effects of SF on I/R retinas. Together, we offer direct evidence that SF had protective effects on I/R retinas, which could be attributed, at least in part, to the activation of the Nrf2/HO-1 antioxidant pathway.

Counteracting effect of threat on reward enhancements during working memory.

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Choi, Jong Moon; Padmala, Srikanth; Pessoa, Luiz

2015-01-01

Cognitive performance has been shown to be enhanced when performance-based rewards are at stake. On the other hand, task-irrelevant threat processing has been shown to have detrimental effects during several cognitive tasks. Crucially, the impact of reward and threat on cognition has been studied largely independently of one another. Hence, our understanding of how reward and threat simultaneously contribute to performance is incomplete. To fill in this gap, the present study investigated how reward and threat interact with one another during a cognitive task. We found that threat of shock counteracted the beneficial effect of reward during a working memory task. Furthermore, individual differences in self-reported reward-sensitivity and anxiety were linked to the extent to which reward and threat interacted during behaviour. Together, the current findings contribute to a limited but growing literature unravelling how positive and negative information processing jointly influence cognition.

Analysis of the 3’ untranslated regions of α-tubulin and S-crystallin mRNA and the identification of CPEB in dark- and light-adapted octopus retinas

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Kelly, Shannan; Yamamoto, Hideki

2008-01-01

Purpose We previously reported the differential expression and translation of mRNA and protein in dark- and light-adapted octopus retinas, which may result from cytoplasmic polyadenylation element (CPE)–dependent mRNA masking and unmasking. Here we investigate the presence of CPEs in α-tubulin and S-crystallin mRNA and report the identification of cytoplasmic polyadenylation element binding protein (CPEB) in light- and dark-adapted octopus retinas. Methods 3’-RACE and sequencing were used to isolate and analyze the 3’-UTRs of α-tubulin and S-crystallin mRNA. Total retinal protein isolated from light- and dark-adapted octopus retinas was subjected to western blot analysis followed by CPEB antibody detection, PEP-171 inhibition of CPEB, and dephosphorylation of CPEB. Results The following CPE-like sequence was detected in the 3’-UTR of isolated long S-crystallin mRNA variants: UUUAACA. No CPE or CPE-like sequences were detected in the 3’-UTRs of α-tubulin mRNA or of the short S-crystallin mRNA variants. Western blot analysis detected CPEB as two putative bands migrating between 60-80 kDa, while a third band migrated below 30 kDa in dark- and light-adapted retinas. Conclusions The detection of CPEB and the identification of the putative CPE-like sequences in the S-crystallin 3’-UTR suggest that CPEB may be involved in the activation of masked S-crystallin mRNA, but not in the regulation of α-tubulin mRNA, resulting in increased S-crystallin protein synthesis in dark-adapted octopus retinas. PMID:18682811

Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration.

Science.gov (United States)

Ma, Hongwei; Yang, Fan; Butler, Michael R; Belcher, Joshua; Redmond, T Michael; Placzek, Andrew T; Scanlan, Thomas S; Ding, Xi-Qin

2017-08-01

Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, THRA and THRB , encode TRs; THRB 2 has been associated with cone viability. Using TR antagonists and Thrb2 deletion, we examined the effects of TR inhibition. Systemic and ocular treatment with the TR antagonists NH-3 and 1-850 increased cone density by 30-40% in the Rpe65 -/- mouse model of Leber congenital amaurosis and reduced the number of TUNEL + cells. Cone survival was significantly improved in Rpe65 -/- and Cpfl1 (a model of achromatopsia with Pde6c defect) mice with Thrb2 deletion. Ventral cone density in Cpfl1/Thrb2 -/- and Rpe65 -/- / Thrb2 -/- mice was increased by 1- to 4-fold, compared with age-matched controls. Moreover, the expression levels of TR were significantly higher in the cone-degeneration retinas, suggesting locally elevated TR signaling. This work shows that the effects of antithyroid treatment or targeting DIOs were likely mediated by TRs and that suppressing TR protects cones. Our findings support the view that inhibition of TR locally in the retina is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

A Comparative Analysis of the Endocannabinoid System in the Retina of Mice, Tree Shrews, and Monkeys

DEFF Research Database (Denmark)

Bouskila, Joseph; Javadi, Pasha; Elkrief, Laurent

2016-01-01

is known about the distribution of the enzymes involved in the synthesis and degradation of these eCBs. We therefore examined the expression and localization of the main components of the eCB system in the retina of mice, tree shrews, and monkeys. We found that CB1R and FAAH distributions are well...

Activation of the Nrf2/HO-1 Antioxidant Pathway Contributes to the Protective Effects of Lycium Barbarum Polysaccharides in the Rodent Retina after Ischemia-Reperfusion-Induced Damage

Science.gov (United States)

Chang, Raymond Chuen-Chung; So, Kwok-Fai; Brecha, Nicholas C.; Pu, Mingliang

2014-01-01

Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are protective to retina after ischemia-reperfusion (I/R). The antioxidant response element (ARE)–mediated antioxidant pathway plays an important role in maintaining the redox status of the retina. Heme oxygenase-1 (HO-1), combined with potent AREs in its promoter, is a highly effective therapeutic target for the protection against neurodegenerative diseases, including I/R-induced retinal damage. The aim of our present study was to investigate whether the protective effect of LBP after I/R damage was mediated via activation of the Nrf2/HO-1-antioxidant pathway in the retina. Retinal I/R was induced by an increase in intraocular pressure to 130 mm Hg for 60 minutes. Prior to the induction of ischemia, rats were orally treated with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. For specific experiments, zinc protoporphyrin (ZnPP, 20 mg/kg), an HO-1 inhibitor, was intraperitoneally administered at 24 h prior to ischemia. The protective effects of LBP were evaluated by quantifying ganglion cell and amacrine cell survival, and by measuring cell apoptosis in the retinal layers. In addition, HO-1 expression was examined using Western blotting and immunofluorescence analyses. Cytosolic and nuclear Nrf2 was measured using immunofluorescent staining. LBP treatment significantly increased Nrf2 nuclear accumulation and HO-1 expression in the retina after I/R injury. Increased apoptosis and a decrease in the number of viable cells were observed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in the I/R retina, which were reversed by LBP treatment. The HO-1 inhibitor, ZnPP, diminished the LBP treatment-induced protective effects in the retina after I/R. Taken together, these results suggested that LBP partially exerted its beneficial neuroprotective effects via the activation of Nrf2 and an increase in HO-1 protein expression. PMID:24400114

Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina.

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Choi, Hannah; Zhang, Lei; Cembrowski, Mark S; Sabottke, Carl F; Markowitz, Alexander L; Butts, Daniel A; Kath, William L; Singer, Joshua H; Riecke, Hermann

2014-09-15

In many forms of retinal degeneration, photoreceptors die but inner retinal circuits remain intact. In the rd1 mouse, an established model for blinding retinal diseases, spontaneous activity in the coupled network of AII amacrine and ON cone bipolar cells leads to rhythmic bursting of ganglion cells. Since such activity could impair retinal and/or cortical responses to restored photoreceptor function, understanding its nature is important for developing treatments of retinal pathologies. Here we analyzed a compartmental model of the wild-type mouse AII amacrine cell to predict that the cell's intrinsic membrane properties, specifically, interacting fast Na and slow, M-type K conductances, would allow its membrane potential to oscillate when light-evoked excitatory synaptic inputs were withdrawn following photoreceptor degeneration. We tested and confirmed this hypothesis experimentally by recording from AIIs in a slice preparation of rd1 retina. Additionally, recordings from ganglion cells in a whole mount preparation of rd1 retina demonstrated that activity in AIIs was propagated unchanged to elicit bursts of action potentials in ganglion cells. We conclude that oscillations are not an emergent property of a degenerated retinal network. Rather, they arise largely from the intrinsic properties of a single retinal interneuron, the AII amacrine cell. Copyright © 2014 the American Physiological Society.

Cell Cycle Regulation and Apoptotic Responses of the Embryonic Chick Retina by Ionizing Radiation.

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Margot Mayer

Full Text Available Ionizing radiation (IR exerts deleterious effects on the developing brain, since proliferative neuronal progenitor cells are highly sensitive to IR-induced DNA damage. Assuming a radiation response that is comparable to mammals, the chick embryo would represent a lower vertebrate model system that allows analysis of the mechanisms underlying this sensitivity, thereby contributing to the reduction, refinement and replacement of animal experiments. Thus, this study aimed to elucidate the radiation response of the embryonic chick retina in three selected embryonic stages. Our studies reveal a lack in the radiation-induced activation of a G1/S checkpoint, but rapid abrogation of G2/M progression after IR in retinal progenitors throughout development. Unlike cell cycle control, radiation-induced apoptosis (RIA showed strong variations between its extent, dose dependency and temporal occurrence. Whereas the general sensitivity towards RIA declined with ongoing differentiation, its dose dependency constantly increased with age. For all embryonic stages RIA occurred during comparable periods after irradiation, but in older animals its maximum shifted towards earlier post-irradiation time points. In summary, our results are in good agreement with data from the developing rodent retina, strengthening the suitability of the chick embryo for the analysis of the radiation response in the developing central nervous system.

Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2 diabetes mellitus model

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Rui-Jin Ran

2016-11-01

Full Text Available AIM: To examine the expression of high mobility group box-1 (HMGB-1 and intercellular adhesion molecule-1 (ICAM-1 in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier (BRB and blood-brain barrier (BBB in a rat model of type 2 diabetes. METHODS: The type-2 diabetes mellitus (DM model was established with a high-fat and high-glucose diet combined with streptozotocin (STZ. Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay (ELISA. RESULTS: A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection (P＜0.01. The serum levels of fasting insulin, Insulin resistance homeostatic model assessment (IRHOMA, total cholesterol (TC, total triglycerides (TG and low density lipoprotein cholesterol (LDL-C in the DM rats significantly higher than those in the controls (all P＜0.01. HMGB-1 (0.96±0.03, P＜0.01 and ICAM-1 (0.76±0.12, P＜0.05 levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1 (0.83±0.13, P＜0.01 and ICAM-1 (1.15±0.08, P＜0.01 levels in the hippocampal tissues in the DM rats were also significantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls (P＜0.01. However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats. CONCLUSION: BRB permeability increases significantly

Differences in Pre and Post Vascular Patterning Within Retinas from ISS Crew Members and Head-Down Tilt (HDT) Subjects by VESGEN Analysis

Science.gov (United States)

Murray, M. C.; Vizzeri, G.; Taibbi, G.; Mason, S. S.; Young, M.; Zanello, S. B.; Parsons-Wingerter, P.

2018-01-01

Accelerated research by NASA has investigated the significant risks incurred during long-duration missions in microgravity for Space Flight-Associated Neuro-ocular Syndrome (SANS, formerly known as Visual Impairments associated with Increased Intracranial Pressure, VIIP) [1]. For our study, NASA's VESsel GENeration Analysis (VESGEN) was used to investigate the role of retinal blood vessels in the etiology of SANS/VIIP. The response of retinal vessels to microgravity was evaluated in astronaut crew members pre and post flight to the International Space Station (ISS), and compared to the response of retinal vessels in healthy volunteers to 6deg head-down tilt during 70 days of bed rest (HDTBR). For the study, we are testing the hypothesis that long-term cephalad fluid shifts resulting in ocular and visual impairments are necessarily mediated in part by retinal blood vessels, and therefore are accompanied by structural adaptations of the vessels. METHODS: Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30deg infrared (IR) Heidelberg Spectralis images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). VESGEN is a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues. The multi-parametric VESGEN analysis generates maps of branching arterial and venous trees quantified by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations according to vascular physiological branching rules. The retrospective study approved by NASA's Institutional Review Board included the analysis of bilateral retinas in eight ISS crew members monitored by routine occupational surveillance and six HDTBR subjects (NASA FARU Campaign 11, for example). The VESGEN analysis was conducted in a

Patterns of cell proliferation and cell death in the developing retina and optic tectum of the brown trout.

NARCIS (Netherlands)

Candal, E.; Anadon, R.; Grip, W.J. de; Rodriguez-Moldes, I.

2005-01-01

We have analyzed the patterns of cell proliferation and cell death in the retina and optic tectum of the brown trout (Salmo trutta fario) throughout embryonic and postembryonic stages. Cell proliferation was detected by immunohistochemistry with an antibody against the proliferating cell nuclear

Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients

DEFF Research Database (Denmark)

Klassen, Henry; Kiilgaard, Jens Folke; Zahir, Tasneem

2007-01-01

Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor...

Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD.

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Wenxin Ma

2009-11-01

Full Text Available Age-related macular degeneration (AMD is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD.In this study, we examined the effects of retinal microglia on RPE cells using 1 an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2 an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1 changes in RPE structure and distribution, 2 increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3 increased extent of in vivo choroidal neovascularization in the subretinal space.These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.

Simulated annealing in adaptive optics for imaging the eye retina

International Nuclear Information System (INIS)

Zommer, S.; Adler, J.; Lipson, S. G.; Ribak, E.

2004-01-01

Full Text:Adaptive optics is a method designed to correct deformed images in real time. Once the distorted wavefront is known, a deformable mirror is used to compensate the aberrations and return the wavefront to a plane wave. This study concentrates on methods that omit wave front sensing from the reconstruction process. Such methods use stochastic algorithms to find the extremum of a certain sharpness function, thereby correcting the image without any information on the wavefront. Theoretical work [l] has shown that the optical problem can be mapped onto a model for crystal roughening. The main algorithm applied is simulated annealing. We present a first hardware realization of this algorithm in an adaptive optics system designed to image the retina of the human eye

Smoking Counteracts the Favorable Effect of Exercise Training on Endothelial Function in Patients with Type 2 Diabetes

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Shinji Sato

2013-01-01

Full Text Available Background Exercise training can improve endothelial function in patients with diabetes. We hypothesized that the favorable effect of exercise training on endothelial function in patients with diabetes is counteracted by cigarette smoking. Purpose To assess whether there is a difference in the effect of exercise on endothelial function in smokers and non-smokers with type 2 diabetes. Methods We performed a 3-month controlled trial in 27 never-smoking and 17 smoking individuals with type 2 diabetes who participated in a home-based walking program. The percentage decrease in post-exercise ankle-brachial pressure index (ABI, which is an index of endothelial function, was assessed at baseline and after 3 months. Results Compared to the smoking group, the never-smoking group showed a more significant improvement in post exercise ABI during the 3 months of home-based training (interaction, P < 0.01. Conclusions These results indicate that smoking may counteract the favorable effects of exercise training on endothelial function. Endothelial function plays an important role in the prevention of cardiovascular disease among patients with diabetes. Therefore, a Certified Diabetes Educator should strongly advise diabetic patients not to smoke.

Trans-Corneal Subretinal Injection in Mice and Its Effect on the Function and Morphology of the Retina.

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Yan Qi

Full Text Available To introduce a practical method of subretinal injection in mice and evaluate injection-induced retinal detachment (RD and damage using a dynamic imaging system, electrophysiology, and histology.After full dilation of a 2-month-old C57BL/6J mouse pupil, the cornea near the limbus was punctured with a 30 ½-gague disposable beveled needle. A 33 ½-gauge blunt needle was inserted through the corneal perforation into the anterior chamber, avoiding the lens before going deeper into the vitreous cavity, and penetrating the inner retina to reach the subretinal space. The mice were divided into four groups: in group 1, about 80-100% of the retina was filled with subretinally injected solution; in group 2, approximately 50-70% of the retina was filled with injected solution; in group 3, the procedures were stopped before solution injection; and non-injected eyes were used as the negative control in group 4. An optical coherence tomography (OCT imaging system was used to monitor retinal reattachment during the first three days following the injections. Histological and functional changes were examined by light microscopy and electroretinography (ERG at five weeks post-injection.After a short-term training, a 70% success rate with 50% or more coverage (i.e., retinal blebs occupied 50% or more retinal area and filled with the injected solution with minimal injection-related damages can be achieved. Bleb formation was associated with retinal detachment (RD between the neuroretina and the retinal pigment epithelium (RPE layer. Partial RD could be observed at post-injection day 1, and by day 2 most of the retina had reattached. At 5 weeks post-injection, compared to uninjected control group 4, the b-wave amplitudes of ERG decreased 22% in group 1, 16% in group 2, and 7% in group 3; the b-wave amplitudes were statistically different between the uninjected group and the groups with either 50-70% or 80-100% coverage. The subretinal injection-induced RD reattached

Disruption of Fractalkine Signaling Leads to Microglial Activation and Neuronal Damage in the Diabetic Retina

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Sandra M. Cardona

2015-10-01

Full Text Available Fractalkine (CX3CL1 or FKN is a membrane-bound chemokine expressed on neuronal membranes and is proteolytically cleaved to shed a soluble chemoattractant domain. FKN signals via its unique receptor CX3CR1 expressed on microglia and other peripheral leukocytes. The aim of this study is to determine the role of CX3CR1 in inflammatory-mediated damage to retinal neurons using a model of diabetic retinopathy. For this, we compared neuronal, microglial, and astroglial densities and inflammatory response in nondiabetic and diabetic (Ins2Akita CX3CR1-wild-type and CX3CR1-deficient mice at 10 and 20 weeks of age. Our results show that Ins2Akita CX3CR1-knockout mice exhibited (a decreased neuronal cell counts in the retinal ganglion cell layer, (b increased microglial cell numbers, and (c decreased astrocyte responses comparable with Ins2Akita CX3CR1-Wild-type mice at 20 weeks of age. Analyses of the inflammatory response using PCR arrays showed several inflammatory genes differentially regulated in diabetic tissues. From those, the response in Ins2Akita CX3CR1-deficient mice at 10 weeks of age revealed a significant upregulation of IL-1β at the transcript level that was confirmed by enzyme-linked immunosorbent assay in soluble retinal extracts. Overall, IL-1β, VEGF, and nitrite levels as a read out of nitric oxide production were abundant in Ins2Akita CX3CR1-deficient retina. Notably, double immunofluorescence staining shows that astrocytes act as a source of IL-1β in the Ins2Akita retina, and CX3CR1-deficient microglia potentiate the inflammatory response via IL-1β release. Collectively, these data demonstrate that dysregulated microglial responses in absence of CX3CR1 contribute to inflammatory-mediated damage of neurons in the diabetic retina.

Comparison of retina specialist preferences regarding spectral-domain and swept-source optical coherence tomography angiography

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Su GL

2017-05-01

Full Text Available Grace L Su,1 Douglas M Baughman,2 Qinqin Zhang,3 Kasra Rezaei,2 Aaron Y Lee,2 Cecilia S Lee2 1Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 2Department of Ophthalmology, 3Department of Bioengineering, University of Washington, Seattle, WA, USA Purpose: The aim of this study was to compare physician preferences regarding the commercially available spectral-domain (SD optical coherence tomography angiography (OCTA and swept-source (SS OCTA prototype device.Design: Comparative analysis of diagnostic instruments was performed.Patients and methods: Subjects at the University of Washington Eye Institute and Harborview Medical Center were prospectively recruited and imaged with the Zeiss SD OCTA (HD-5000, Angioplex and Zeiss SS OCTA (Plex Elite, Everest devices on the same day. The study included 10 eyes from 10 subjects diagnosed with a retinal/choroidal disease. Deidentified images were compiled into a survey and sent to retina specialists in various countries. The survey presented masked SD and SS images of each eye for each retinal sublayer side by side. Respondents were asked about their image preference and impact on clinical management. A priori and post hoc preferences for SD vs SS were collected.Results: Fifty-four retina specialists responded to the survey. Median years in practice was 3.00 (interquartile range [IQR] 1.50–17.00. At baseline, 23 (48% physicians owned an OCTA machine. The majority of physician responses showed a preference for the SS over SD OCTA, independent of the retinal pathology shown (n=454 overall responses, 74%. Nevertheless, the majority indicated that both SD and SS would be equally valuable in informing clinical decisions (n=374 overall responses, 61%.Conclusion: These findings indicate that the majority of retina specialists surveyed prefer SS over SD OCTA based on image quality, regardless of the retinal pathology shown. Regarding the clinical utility of each modality, the majority of

Some Problems of the Implementation of Administrative Responsibility for Violations of the Legislation on Contract System in the Procurement Sphere

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Andrei E. Yuritsin

2017-12-01

Full Text Available The article considers the issues of application of Article 6.9 of the Code of Administrative Offences of the Russian Federation and the significance of the practice of implementation of this legal norm to counteraction to illegal drug use. The author estimates the possibility of dealing all cases of illegal use of narcotic drugs and psychotropic substances and their analogues by law enforcement practice as well as the sufficiency of administrative penalties provided for by the Article. Critical evaluation is given to the suitability of criminalization of systematic illegal drug use. The significance of Article 6.9 of the Code of Administrative Offences of RF is connected with the demonstration of the state policy vector regarding illegal drug use, the substantiation of possibility of applying certain measures of state coercion, as well as with the legal statement of the fact of unlawful act and the change of environment in which the offender realizes his/her rights and obligations.

Feasibility study of Raman spectroscopy for investigating the mouse retina in vivo

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Manna, Suman K.; de Oliveira, Marcos A. S.; Zhang, Pengfei; Maleppat, Ratheesh K.; Chang, Che-Wei; Pugh, Edward N.; Chan, James W.; Zawadzki, Robert J.

2018-02-01

The use of Raman spectroscopy in biochemistry has been very successful, particularly because of its ability to identify elementary chemical species. However, application of this spectroscopic technique for in vivo assessment is often limited by autofluorescence, which make detection of Raman signatures difficult. The mouse eye has been used as an optical testbed for investigation of a variety of disease models and therapeutic pathways. Implementation of in vivo Raman spectroscopy in mice retina would be valuable but needs to be examined in context of the intrinsic auto-fluorescence artifact and potential light damage if high probing beam powers were used. To evaluate feasibility, a Raman system was built on a custom SLO/OCT platform allowing mouse positioning and morphological data acquisition along with the Raman signal from a desired retinal eccentricity. The performance of the Raman system was first assessed with a model eye consisting of polystyrene in the image plane (retina), using excitation wavelengths of 488 nm, 561 nm, and 785 nm to determine whether auto-fluorescence would be reduced at longer wavelengths. To improve the SNR, the combined system is featured with the optical compatibility for these three excitations such that their corresponding spectra from a typical region of interest can be acquired consecutively during single imaging run. Our results include emission spectra acquired over 10 s with excitation energy less than 160 J.s-1.m-2 for all wavelengths and corresponding retinal morphology for different mouse strains including WT, BALB/c and ABCA4-/-.

Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNγ Secretion.

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Rode, Anna K O; Kongsbak, Martin; Hansen, Marie M; Lopez, Daniel Villalba; Levring, Trine B; Woetmann, Anders; Ødum, Niels; Bonefeld, Charlotte M; Geisler, Carsten

2017-01-01

Tuberculosis (TB) presents a serious health problem with approximately one-third of the world's population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas. Paradoxically, vitamin D has repeatedly been ascribed an immune-suppressive function inhibiting Th1 differentiation and production of IFNγ in T cells. The aim of this study was to investigate this apparent paradox. We studied naïve human CD4 + T cells activated either with CD3 and CD28 antibodies or with allogeneic dendritic cells (DC) stimulated with heat-killed M. tuberculosis (HKMT) or purified toll-like receptor (TLR) ligands. We show that vitamin D does not block differentiation of human CD4 + T cells to Th1 cells and that interleukin (IL)-12 partially counteracts vitamin D-mediated inhibition of IFNγ production promoting production of equal amounts of IFNγ in Th1 cells in the presence of vitamin D as in T cells activated in the absence of vitamin D and IL-12. Furthermore, we show that HKMT and TLR2 ligands strongly downregulate cathelicidin expression in DC and that vitamin D counteracts this by upregulating cathelicidin expression. In conclusion, we demonstrate that vitamin D counteracts M. tuberculosis -induced cathelicidin downregulation and allows Th1 differentiation and IFNγ secretion.

Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNγ Secretion

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Anna K. O. Rode

2017-05-01

Full Text Available Tuberculosis (TB presents a serious health problem with approximately one-third of the world’s population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas. Paradoxically, vitamin D has repeatedly been ascribed an immune-suppressive function inhibiting Th1 differentiation and production of IFNγ in T cells. The aim of this study was to investigate this apparent paradox. We studied naïve human CD4+ T cells activated either with CD3 and CD28 antibodies or with allogeneic dendritic cells (DC stimulated with heat-killed M. tuberculosis (HKMT or purified toll-like receptor (TLR ligands. We show that vitamin D does not block differentiation of human CD4+ T cells to Th1 cells and that interleukin (IL-12 partially counteracts vitamin D-mediated inhibition of IFNγ production promoting production of equal amounts of IFNγ in Th1 cells in the presence of vitamin D as in T cells activated in the absence of vitamin D and IL-12. Furthermore, we show that HKMT and TLR2 ligands strongly downregulate cathelicidin expression in DC and that vitamin D counteracts this by upregulating cathelicidin expression. In conclusion, we demonstrate that vitamin D counteracts M. tuberculosis-induced cathelicidin downregulation and allows Th1 differentiation and IFNγ secretion.

Gene expression changes in the retina following subretinal injection of human neural progenitor cells into a rodent model for retinal degeneration.

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Jones, Melissa K; Lu, Bin; Saghizadeh, Mehrnoosh; Wang, Shaomei

2016-01-01

Retinal degenerative diseases (RDDs) affect millions of people and are the leading cause of vision loss. Although treatment options for RDDs are limited, stem and progenitor cell-based therapies have great potential to halt or slow the progression of vision loss. Our previous studies have shown that a single subretinal injection of human forebrain derived neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) retinal degenerate rat offers long-term preservation of photoreceptors and visual function. Furthermore, neural progenitor cells are currently in clinical trials for treating age-related macular degeneration; however, the molecular mechanisms of stem cell-based therapies are largely unknown. This is the first study to analyze gene expression changes in the retina of RCS rats following subretinal injection of hNPCs using high-throughput sequencing. RNA-seq data of retinas from RCS rats injected with hNPCs (RCS(hNPCs)) were compared to sham surgery in RCS (RCS(sham)) and wild-type Long Evans (LE(sham)) rats. Differential gene expression patterns were determined with in silico analysis and confirmed with qRT-PCR. Function, biologic, cellular component, and pathway analyses were performed on differentially expressed genes and investigated with immunofluorescent staining experiments. Analysis of the gene expression data sets identified 1,215 genes that were differentially expressed between RCS(sham) and LE(sham) samples. Additionally, 283 genes were differentially expressed between the RCS(hNPCs) and RCS(sham) samples. Comparison of these two gene sets identified 68 genes with inverse expression (termed rescue genes), including Pdc, Rp1, and Cdc42ep5. Functional, biologic, and cellular component analyses indicate that the immune response is enhanced in RCS(sham). Pathway analysis of the differential expression gene sets identified three affected pathways in RCS(hNPCs), which all play roles in phagocytosis signaling. Immunofluorescent staining

Nervus terminalis projection to the retina in the 'four-eyed' fish, Anableps anableps.

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Meyer, D L; Malz, C R; Jadhao, A G

1996-08-02

The eye of the surface dwelling 'four-eyed' fish, Anableps possesses an aquatic and an aerial optical system. The aerial system is strongly hyperopic when the animal dives, i.e. during mating, and the dorsal pupil is submerged. We studied the retino-petal nervus terminals projection to the aerial and to the aquatic retina by Phe-Met-Arg-Phe-NH2 (FMRF) immunocytochemistry and found both to be equally innervated. This finding sheds doubt on the proposed functional significance of this projection for reproductive behaviour.

The cone-dominant retina and the inner ear of zebrafish express the ortholog of CLRN1, the causative gene of human Usher syndrome type 3A.

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Phillips, Jennifer B; Västinsalo, Hanna; Wegner, Jeremy; Clément, Aurélie; Sankila, Eeva-Marja; Westerfield, Monte

2013-12-01

Clarin-1 (CLRN1) is the causative gene in Usher syndrome type 3A, an autosomal recessive disorder characterized by progressive vision and hearing loss. CLRN1 encodes Clarin-1, a glycoprotein with homology to the tetraspanin family of proteins. Previous cell culture studies suggest that Clarin-1 localizes to the plasma membrane and interacts with the cytoskeleton. Mouse models demonstrate a role for the protein in mechanosensory hair bundle integrity, but the function of Clarin-1 in hearing remains unclear. Even less is known of its role in vision, because the Clrn1 knockout mouse does not exhibit a retinal phenotype and expression studies in murine retinas have provided conflicting results. Here, we describe cloning and expression analysis of the zebrafish clrn1 gene, and report protein localization of Clarin-1 in auditory and visual cells from embryonic through adult stages. We detect clrn1 transcripts as early as 24h post-fertilization, and expression is maintained through adulthood. In situ hybridization experiments show clrn1 transcripts enriched in mechanosensory hair cells and supporting cells of the inner ear and lateral line organ, photoreceptors, and cells of the inner retina. In mechanosensory hair cells, Clarin-1 is polarized to the apical cell body and the synapses. In the retina, Clarin-1 localizes to lateral cell contacts between photoreceptors and is associated with the outer limiting membrane and subapical processes emanating from Müller glial cells. We also find Clarin-1 protein in the outer plexiform, inner nuclear and ganglion cell layers of the retina. Given the importance of Clarin-1 function in the human retina, it is imperative to find an animal model with a comparable requirement. Our data provide a foundation for exploring the role of Clarin-1 in retinal cell function and survival in a diurnal, cone-dominant species. Copyright © 2013 Elsevier B.V. All rights reserved.