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Retinal Ganglion Cells (retinal + ganglion_cell)
Kinds of Retinal Ganglion Cells Selected AbstractsSupport for the idea that light is a risk factor in optic neuropathies, like glaucomaACTA OPHTHALMOLOGICA, Issue 2007NN OSBORNE Purpose: Retinal ganglion cell (RGC) axons in the globe contain many mitochondria and it has been hypothesised that light can interact with these organelles to affect RGC survival in glaucoma. Studies on different cell-types were conducted to support such a proposition. Methods: Near confluent cultures of RGC-5 cells, primary rat retinal cultures, fibroblasts with normal (BJhTERT) or mitochondria depleted of mtDNA (rho0) were transferred to incubators containing light (400-760nm; 800-2000 lux; generally 2 days). Some of the cultures were covered with white paper to exclude the light. The cultures were then analysed for cell viability, generation of free radicals (ROS) and for death by apoptosis. Results: Oxidative status and mitochondrial dehydrogenase activity in retinal cultures (-40±5%), RGC-5 cells (-20±4%) and BJhTERT cells (-13±3%) was reduced significantly by light. Light reduced the number of GABA-positive neurones (-42±6%) in retinal cultures. Light caused a 3-5 fold increase in TUNEL-positive cells in primary retinal, RGC-5 and BJhTERT cultures, than in the dark. ROS staining was also clearly elevated by light. The light-induced toxic effect on the different cell types was significantly blunted by antioxidants like vitamin E and lipoic acid. Moreover, light-induced apoptosis was caspase independent but PARP dependent. In contrast, rho0 cells that lacked functional mitochondria were unaffected by light. Conclusions: The present study shows that light can directly affect mitochondrial function to induce apoptosis. This supports the view that light can interact with the many RGC axon mitochondria to affect the viability of GCs and that this may be of significance in the progression of glaucoma. [source] Expression of multiple class three semaphorins in the retina and along the path of zebrafish retinal axonsDEVELOPMENTAL DYNAMICS, Issue 10 2007Davon C. Callander Abstract Retinal ganglion cells (RGCs) extend axons that exit the eye, cross the midline at the optic chiasm, and synapse on target cells in the optic tectum. Class three semaphorins (Sema3s) are a family of molecules known to direct axon growth. We undertook an expression screen to identify sema3s expressed in the retina and/or brain close to in-growing RGC axons, which might therefore influence retinal-tectal pathfinding. We find that sema3Aa, 3Fa, 3Ga, and 3Gb are expressed in the retina, although only sema3Fa is present during the time window when the axons extend. Also, we show that sema3Aa and sema3E are present near or at the optic chiasm. Furthermore, sema3C, 3Fa, 3Ga, and 3Gb are expressed in regions of the diencephalon near the path taken by RGC axons. Finally, the optic tectum expresses sema3Aa, 3Fa, 3Fb, and 3Gb. Thus, sema3s are spatiotemporally placed to influence RGC axon growth. Developmental Dynamics 236:2918,2924, 2007. © 2007 Wiley-Liss, Inc. [source] Intravitreal treatment with Erythropoietin (EPO) preserves visual function following ocular ischemia in ratsACTA OPHTHALMOLOGICA, Issue 2007R DERSCH Purpose: Erythropoetin (EPO) is a promising neuroprotective drug. It is known that EPO reduces apoptosis of retinal ganglion cells following axotomy or glaucoma in rats. Until now, functional aspects of this neuroprotective effect have not been addressed. We investigated effects of EPO on retinal and optic nerve function and on the survival of retinal ganglion cells following ocular ischemia. Methods: Ocular ischemia was induced by increase of the IOP to 120mmHg for 55 min in Brown-Norway rats. Animals were treated intravitreally with 4U/eye (n=12) during the time of ischemia, controls (n=16) recieved BSS instead. Visual pathway was investigated by VEP 4 days after ischemia. Potentials were evoked by frequency and luminance modulated flicker stimuli and recorded in awake freely-moving rats. Retinal function was evaluated by ERG 7 days after ischemia. Retinal ganglion cells were labelled retrogradelly 4 days after ischemia and were quantified 6 days later in retinal flatmounts. Results: Both frequency and luminance modulated evoked potentials increased due to the application of EPO from 6±2% (mean in percent of the non-ischemic eye ± standard error) in control to 46±8% in treated animals and from 26±5% to 69±6% respectively. EPO increased responses of ischemic eyes from 31±6,V to 96±8,V (a-wave) and from 34±6,V to 110±15,V (b-wave). Morphologically, the intravitreal administration of EPO increased the number of surviving ganglion cells from 32±4% to 92±11%. Conclusions: We found a sizable functional benefit of intravitreal injection of EPO following interruption of ocular blood supply. This suggests that administration of EPO is a viable therapeutic option in ischemic retinal diseases. [source] Tenascin-R and axon growth-promoting molecules are up-regulated in the regenerating visual pathway of the lizard (Gallotia galloti)DEVELOPMENTAL NEUROBIOLOGY, Issue 7 2008Dirk M. Lang Abstract It is currently unclear whether retinal ganglion cell (RGC) axon regeneration depends on down-regulation of axon growth-inhibitory proteins, and to what extent outgrowth-promoting substrates contribute to RGC axon regeneration in reptiles. We performed an immunohistochemical study of the regulation of the axon growth-inhibiting extracellular matrix molecules tenascin-R and chondroitin sulphate proteoglycan (CSPG), the axon outgrowth-promoting extracellular matrix proteins fibronectin and laminin, and the axonal tenascin-R receptor protein F3/contactin during RGC axon regeneration in the lizard, Gallotia galloti. Tenascin-R and CSPG were expressed in an extracellular matrix-, oligodendrocyte/myelin- and neuron-associated pattern and up-regulated in the regenerating optic pathway. The expression pattern of tenascin-R was not indicative of a role in channeling or restriction of re-growing RGC axons. Up-regulation of fibronectin, laminin, and F3/contactin occurred in spatiotemporal patterns corresponding to tenascin-R expression. Moreover, we analyzed the influence of substrates containing tenascin-R, fibronectin, and laminin on outgrowth of regenerating lizard RGC axons. In vitro regeneration of RGC axons was not inhibited by tenascin-R, and further improved on mixed substrates containing tenascin-R together with fibronectin or laminin. These results indicate that RGC axon regeneration in Gallotia galloti does not require down-regulation of tenascin-R or CSPG. Presence of tenascin-R is insufficient to prevent RGC axon growth, and concomitant up-regulation of axon growth-promoting molecules like fibronectin and laminin may override the effects of neurite growth inhibitors on RGC axon regeneration. Up-regulation of contactin in RGCs suggests that tenascin-R may have an instructive function during axon regeneration in the lizard optic pathway. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] Ganglion cell regeneration following whole-retina destruction in zebrafishDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2008Tshering Sherpa Abstract The retinas of adult teleost fish can regenerate neurons following injury. The current study provides the first documentation of functional whole retina regeneration in the zebrafish, Danio rerio, following intraocular injection of the cytotoxin, ouabain. Loss and replacement of laminated retinal tissue was monitored by analysis of cell death and cell proliferation, and by analysis of retina-specific gene expression patterns. The spatiotemporal process of retinal ganglion cell (RGC) regeneration was followed through the use of selective markers, and was found to largely recapitulate the spatiotemporal process of embryonic ganglion cell neurogenesis, over a more protracted time frame. However, the re-expression of some ganglion cell markers was not observed. The growth and pathfinding of ganglion cell axons was evaluated by measurement of the optic nerve head (ONH), and the restoration of normal ONH size was found to correspond to the time of recovery of two visually-mediated behaviors. However, some abnormalities were noted, including overproduction of RGCs, and progressive and excessive growth of the ONH at longer recovery times. This model system for whole-retina regeneration has provided an informative view of the regenerative process. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] GABA and development of the Xenopus optic projectionDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2002Shane C. D. Ferguson Abstract In the developing visual system of Xenopus laevis retinal ganglion cell (RGC) axons extend through the brain towards their major target in the midbrain, the optic tectum. Enroute, the axons are guided along their pathway by cues in the environment. In vitro, neurotransmitters have been shown to act chemotropically to influence the trajectory of extending axons and regulate the outgrowth of developing neurites, suggesting that they may act to guide or modulate the growth of axons in vivo. Previous work by Roberts and colleagues (1987) showed that populations of cells within the developing Xenopus diencephalon and midbrain express the neurotransmitter gamma amino butyric acid (GABA). Here we show that Xenopus RGC axons in the midoptic tract grow alongside the GABAergic cells and cross their GABA immunopositive nerve processes. Moreover, RGC axons and growth cones express GABA-A and GABA-B receptors, and GABA and the GABA-B receptor agonist baclofen both stimulate RGC neurite outgrowth in culture. Finally, the GABA-B receptor antagonist CGP54626 applied to the developing optic projection in vivo causes a dose-dependent shortening of the optic projection. These data indicate that GABA may act in vivo to stimulate the outgrowth of Xenopus RGC axons along the optic tract. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 272,284, 2002 [source] Cooperative effects of bcl-2 and AAV-mediated expression of CNTF on retinal ganglion cell survival and axonal regeneration in adult transgenic miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Simone G. Leaver Abstract We used a gene therapy approach in transgenic mice to assess the cooperative effects of combining anti-apoptotic and growth-promoting stimuli on adult retinal ganglion cell (RGC) survival and axonal regeneration following intraorbital optic nerve injury. Bi- cistronic adeno-associated viral vectors encoding a secretable form of ciliary neurotrophic factor and green fluorescent protein (AAV-CNTF-GFP) were injected into eyes of mice that had been engineered to over-express the anti-apoptotic protein bcl-2. For comparison this vector was also injected into wildtype (wt) mice, and both mouse strains were injected with control AAV encoding GFP. Five weeks after optic nerve injury we confirmed that bcl-2 over-expression by itself promoted the survival of axotomized RGCs, but in contrast to previous reports we also saw regeneration of some mature RGC axons beyond the optic nerve crush. AAV-mediated expression of CNTF in adult retinas significantly increased the survival and axonal regeneration of RGCs following axotomy in wt and bcl-2 transgenic mice; however, the effects were greatest in the transgenic strain. Compared with AAV-GFP-injected bcl-2 mice, RGC viability was increased by about 50% (mean, 36 738 RGCs per retina), and over 1000 axons per optic nerve regenerated 1,1.5 mm beyond the crush. These findings exemplify the importance of using a multifactorial therapeutic approach that enhances both neuroprotection and regeneration after central nervous system injury. [source] Early neural activity and dendritic growth in turtle retinal ganglion cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006Vandana Mehta Abstract Early neural activity, both prenatal spontaneous bursts and early visual experience, is believed to be important for dendritic proliferation and for the maturation of neural circuitry in the developing retina. In this study, we have investigated the possible role of early neural activity in shaping developing turtle retinal ganglion cell (RGC) dendritic arbors. RGCs were back-labelled from the optic nerve with horseradish peroxidase (HRP). Changes in dendritic growth patterns were examined across development and following chronic blockade or modification of spontaneous activity and/or visual experience. Dendrites reach peak proliferation at embryonic stage 25 (S25, one week before hatching), followed by pruning in large field RGCs around the time of hatching. When spontaneous activity is chronically blocked in vivo from early embryonic stages (S22) with curare, a cholinergic nicotinic antagonist, RGC dendritic growth is inhibited. On the other hand, enhancement of spontaneous activity by dark-rearing (Sernagor & Grzywacz (1996)Curr. Biol., 6, 1503,1508) promotes dendritic proliferation in large-field RGCs, an effect that is counteracted by exposure to curare from hatching. We also recorded spontaneous activity from individual RGCs labelled with lucifer yellow (LY). We found a tendency of RGCs with large dendritic fields to be spontaneously more active than small-field cells. From all these observations, we conclude that immature spontaneous activity promotes dendritic growth in developing RGCs. [source] Expression of glial fibrillary acidic protein and glutamine synthetase by Müller cells after optic nerve damage and intravitreal application of brain-derived neurotrophic factorGLIA, Issue 2 2002Hao Chen Abstract Müller glia play an important role in maintaining retinal homeostasis, and brain-derived neurotrophic factor (BDNF) has proven to be an effective retinal ganglion cell (RGC) neuroprotectant following optic nerve injury. The goal of these studies was to investigate the relation between optic nerve injury and Müller cell activation, and to determine the extent to which BDNF affects the injury response of Müller cells. Using immunocytochemistry and Western blot analysis, temporal changes in the expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) were examined in rats after optic nerve crush alone, or in conjunction with an intravitreal injection of BDNF (5 ,g). GFAP protein levels were normal at 1 day post-crush, but increased ,9-fold by day 3 and remained elevated over the 2-week period studied. Müller cell GS expression remained stable after optic nerve crush, but the protein showed a transient shift in its cellular distribution; during the initial 24-h period post-crush the GS protein appeared to translocate from the cell body to the inner and outer glial processes, and particularly to the basal endfeet located in the ganglion cell layer. BDNF alone, or in combination with optic nerve crush, did not have a significant effect on the expression of either GFAP or GS compared with the normal retina, or after optic nerve crush alone, respectively. The data indicate that although BDNF is a potent neuroprotectant in the vertebrate retina, it does not appear to have a significant influence on Müller cell expression of either GS or GFAP in response to optic nerve injury. GLIA 38:115,125, 2002. © 2002 Wiley-Liss, Inc. [source] Expression of neuronal markers, synaptic proteins, and glutamine synthetase in the control and regenerating lizard visual systemTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 19 2010M.M. Romero-Alemįn Abstract Spontaneous regrowth of retinal ganglion cell (RGC) axons occurs after optic nerve (ON) transection in the lizard Gallotia galloti. To gain more insight into this event we performed an immunohistochemical study on selected neuron and glial markers, which proved useful for analyzing the axonal regrowth process in different regeneration models. In the control lizards, RGCs were beta-III tubulin- (Tuj1) and HuCD-positive. The vesicular glutamate transporter-1 (VGLUT1) preferentially stained RGCs and glial somata rather than synaptic layers. In contrast, SV2 and vesicular GABA/glycine transporter (VGAT) labeling was restricted to both plexiform layers. Strikingly, the strong expression of glutamine synthetase (GS) in both Müller glia processes and macroglial somata revealed a high glutamate metabolism along the visual system. Upregulation of Tuj1 and HuCD in the surviving RGCs was observed at all the timepoints studied (1, 3, 6, 9, and 12 months postlesion). The significant rise of Tuj1 in the optic nerve head and optic tract (OTr) by 1 and 6 months postlesion, respectively, suggests an increase of the beta-III tubulin transport and incorporation into newly formed axons. Persistent Tuj1+ and SV2+ puncta and swellings were abnormally observed in putative degenerating/dystrophic fibers. Unexpectedly, neuron-like cells of obscure significance were identified in the control and regenerating ON-OTr. We conclude that: 1) the persistent upregulation of Tuj1 and HuCD favors the long-lasting axonal regrowth process; 2) the latter succeeded despite the ectopia and dystrophy of some regrowing fibers; and 3) maintenance of the glutamate-glutamine cycle contributes to the homeostasis and plasticity of the system. J. Comp. Neurol. 518:4067,4087, 2010. © 2010 Wiley-Liss, Inc. [source] Selective projection patterns from subtypes of retinal ganglion cells to tectum and pretectum: Distribution and relation to behaviorTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2009Marcus Robert Jones Abstract An important issue to understand is how visual information can influence the motor system and affect behavior. Using the lamprey (Petromyzon marinus) as an experimental model we examined the morphological subtypes of retinal ganglion cells and their projection pattern to the tectum, which controls eye, head, and body movements, and to the pretectum, which mediates both visual escape responses and the dorsal light response. We identified six distinct morphological types of retinal ganglion cell. Four of these distribute their dendrites in the inner plexiform layer (image forming layer) and project in a retinotopic manner to all areas of the tectum. The posterior part of the retina has the highest density of ganglion cells and projects to the rostral part of the tectum, in which the visual field in front of the lamprey will be represented. From this area both orienting and evasive behaviors can be elicited. In contrast, pretectum receives input from two ganglion cells types that send their dendrites only to the outer plexiform layer or the outer limiting membrane and therefore may directly contact photoreceptors, and transmit information without additional delay to pretectum, which may be particularly important for visual escape responses. One of these two types, the bipolar ganglion cell, is only found in a small patch of retina just ventral of the optic nerve. Due to its distribution, morphology, and projections we suggest that this cell may control the dorsal light response. J. Comp. Neurol. 517:257,275, 2009. © 2009 Wiley-Liss, Inc. [source] Selective projection patterns from subtypes of retinal ganglion cells to tectum and pretectum: Distribution and relation to behaviorTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2009Marcus Robert Jones Abstract An important issue to understand is how visual information can influence the motor system and affect behavior. Using the lamprey (Petromyzon marinus) as an experimental model we examined the morphological subtypes of retinal ganglion cells and their projection pattern to the tectum, which controls eye, head, and body movements, and to the pretectum, which mediates both visual escape responses and the dorsal light response. We identified six distinct morphological types of retinal ganglion cell. Four of these distribute their dendrites in the inner plexiform layer (image forming layer) and project in a retinotopic manner to all areas of the tectum. The posterior part of the retina has the highest density of ganglion cells and projects to the rostral part of the tectum, in which the visual field in front of the lamprey will be represented. From this area both orienting and evasive behaviors can be elicited. In contrast, pretectum receives input from two ganglion cells types that send their dendrites only to the outer plexiform layer or the outer limiting membrane and therefore may directly contact photoreceptors, and transmit information without additional delay to pretectum, which may be particularly important for visual escape responses. One of these two types, the bipolar ganglion cell, is only found in a small patch of retina just ventral of the optic nerve. Due to its distribution, morphology, and projections we suggest that this cell may control the dorsal light response. J. Comp. Neurol. 517:257,275, 2009. © 2009 Wiley-Liss, Inc. [source] Selective projection patterns from subtypes of retinal ganglion cells to tectum and pretectum: Distribution and relation to behaviorTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2009Marcus Robert Jones Abstract An important issue to understand is how visual information can influence the motor system and affect behavior. Using the lamprey (Petromyzon marinus) as an experimental model we examined the morphological subtypes of retinal ganglion cells and their projection pattern to the tectum, which controls eye, head, and body movements, and to the pretectum, which mediates both visual escape responses and the dorsal light response. We identified six distinct morphological types of retinal ganglion cell. Four of these distribute their dendrites in the inner plexiform layer (image forming layer) and project in a retinotopic manner to all areas of the tectum. The posterior part of the retina has the highest density of ganglion cells and projects to the rostral part of the tectum, in which the visual field in front of the lamprey will be represented. From this area both orienting and evasive behaviors can be elicited. In contrast, pretectum receives input from two ganglion cells types that send their dendrites only to the outer plexiform layer or the outer limiting membrane and therefore may directly contact photoreceptors, and transmit information without additional delay to pretectum, which may be particularly important for visual escape responses. One of these two types, the bipolar ganglion cell, is only found in a small patch of retina just ventral of the optic nerve. Due to its distribution, morphology, and projections we suggest that this cell may control the dorsal light response. J. Comp. Neurol. 517:257,275, 2009. © 2009 Wiley-Liss, Inc. [source] Synaptic organization of complex ganglion cells in rabbit retina: Type and arrangement of inputs to directionally selective and local-edge-detector cellsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2005Edward V. Famiglietti Abstract The type and topographic distribution of synaptic inputs to a directionally selective (DS) rabbit retinal ganglion cell (GC) were examined and were compared with those received by two other complex GC types. The percentage of cone bipolar cell (BC) input, presumably an index of sustained responses and simple receptive field properties, is much higher than expected for complex GCs in reference to previous reports in other species: approximately 20% for the type 1 bistratified ON,OFF DS GC and for a multistratified GC, and approximately 40% for the small-tufted local-edge-detector GC. Consistent with a previous study (Famiglietti [1991] J. Comp. Neurol. 309:40,70), no ultrastructural evidence is found for inhibitory synapses from starburst amacrine cells to the ON,OFF DS GC. The density of inputs to the ON,OFF DS GC is high and rather evenly distributed over the dendritic tree. Clustering of inputs brings excitatory and inhibitory inputs into proximity, but the strict on-path condition of more proximal inhibitory inputs, favoring shunting inhibition, is not satisfied. Prominent BC input and its regional variation suggest that BCs play key roles in DS neural circuitry, both pre- and postsynaptic to the ON,OFF DS GC, according to a bilayer model (Famiglietti [1993] Invest. Ophthalmol. Vis. Sci. 34:S985). Asymmetry of inhibitory amacrine cell input may signify a region on the preferred side of the receptive field, the inhibition-free zone (Barlow and Levick [1965] J. Physiol. (Lond.) 178:477,504), supporting a role for postsynaptic integration in the DS mechanism. Prominent BC input to the local-edge-detector, often without accompanying amacrine cell input, indicates presynaptic integration in forming its trigger feature. J. Comp. Neurol. 484:357,391, 2005. © 2005 Wiley-Liss, Inc. [source] Dose-Dependent Immunohistochemical Changes in Rat Cornea and Retina after Oral Methylphenidate AdministrationANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2009E. Tunc Summary Methylphenidate hydrochloride (MPH), more commonly known as Ritalin, is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder, one of the most common behavioural disorders of children and young adults. The aim of this study was to investigate dose-dependent immunohistochemical Dopamine 2 receptor (D2) expression and apoptosis in the rat cornea and cornea. In this study, 27 female pre-pubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) and their control groups, were used. They were treated orally with methylphenidate dissolved in saline solution for 5 days per week during 3 months. At the end of the third month, after perfusion fixation, eye tissue was removed. Paraffin sections were collected for immunohistochemical and terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labelling assay studies. In our study, we observed that the cornea D2 receptor reactivity showed a dose-related increase after MPH treatment, especially in basal cells of the epithelium and a dose-dependent decrease in the retinal ganglion cell which was statistically meaningful. Analysis of the cornea thickness results showed no meaningful difference between groups. Apoptotic cell number showed a meaningful increase in the high dose treated group compared to the other groups of the study. The data suggest that Ritalin has degenerative effect on the important functional part of the eye, such as cornea and retina and its activating dopaminergic mechanism via similar neuronal paths, functionally and structurally, to induce morphological changes. As a result, we believe that this morphological changes negatively effecting functional organization of the affected cornea and retina. [source] 2121: Sustained neuroprotection after a single intravitreal injection of PGJ2 in a rodent model of NAIONACTA OPHTHALMOLOGICA, Issue 2010V TOUITOU Purpose Prostaglandin-J2 (PGJ2) has been proposed as a potential neuroprotective agent. We wanted to evaluate the toxicity/efficacy of a single intravitreal (IVT) injection of PGJ2 in a rodent model of nonarteritic anterior ischemic optic neuropathy (NAION). Methods We used the laser-activated rose Bengal induction method to produce AION in Long-Evans rats. We evaluated IVT-PGJ2 retinal and ON toxicity. Following induction, PGJ2 was IVT-injected in the treatment-group. IVT phosphate-buffered-saline (PBS) was used as control. Functional studies (VEP) were performed at baseline and at 7days post-treatment. Structural studies included immunohistochemical (IHC), electron microscopic (EM) analysis of the optic nerve (ON), and stereologic analysis of retinal ganglion cell (RGC) numbers at30 day 30. Results Toxicity: IVT PGJ2 (5 eyes) did not induce any significant functional/structural changes in the retina or ON of treated animals compared with animals injected with PBS (5 eyes) 30 days post-injection. Efficacy: After a single IVT-injection, day7 VEPs in the PGJ2-treatment group (n=7) had amplitudes 103.6% of baseline, whereas the PBS-treated group (n=6) had VEPs that were 42.4% of the baseline. 30days post-stroke, EM of ON from the treatment-group demonstrated significant preservation of axons and decreased demyelination. Stereological RGCcounts confirmed significant (p<0.04) RGC preservation in PGJ2-treated animals (1462.6 cells/µm2) compared w the stroke+PBS group (1156.5 cells/µm2). Conclusion A single IVT of PGJ2 preserves RGCs and their axons, and provides sustained neuroprotection for at least 1 month following initial ischemic event. [source] Choroidal blood flow and retinal ganglion cell function in early glaucomaACTA OPHTHALMOLOGICA, Issue 2009D MARANGONI Purpose To assess subfoveal choroidal blood flow in patients with early manifest glaucoma (EMG) and to compare blood flow with functional measures of retinal ganglion cell (RGC) integrity. Methods Subfoveal choroidal blood flow was determined by confocal, real-time laser Doppler flowmetry in 25 EMG patients (<-6 dB Humphrey mean deviation, age range: 42-64 years, visual acuity: 0.8-1.0) and in 20 age-matched controls. All patients had a therapeutically (topical beta-blockers with or without a prostaglandin) controlled intraocular pressure (IOP <20 mmHg). Subfoveal choroidal blood volume (ChBVol), velocity (ChBVel) and flow (ChBF) were determined as the average of three 60 sec recordings with changes in the DC < 10% between the recordings (DC measures the intensity of the light scattered by the tissue and red blood cells in the illuminated volume). In all patients and controls pattern electroretinograms (PERGs) were recorded according to a standardized protocol. Results In EMG patients, average ChBVel and ChBF were reduced by 31 and 35%, respectively (p <0.01) compared to control values. No significant difference in ChBVol was found between the two groups. PERG amplitudes were reduced by 40% (p <0.01) in EMG patients compared to controls. No correlation was found between anyone of the choroidal flow parameters and PERG data or IOP values. Conclusion The results suggest a significant alteration of subfoveal choroidal hemodynamics in EMG patients, involving both ChBVel and ChBF. These changes do not appear to be associated with the severity of functional retinal ganglion cell loss. Our findings may have implications for the pathophysiology of early glaucomatous damage and its treatment. [source] Functional analysis of mutants of the optineurin gene, associated with some forms of glaucomaACTA OPHTHALMOLOGICA, Issue 2008D BALASUBRAMANIAN Purpose Mutations in the gene OPTN are associated with normal tension and open angle glaucomas. We have studied the effects of some of these mutations on the cellular biology of retinal ganglion cells, and tried to infer the role of the protein optineurin. Methods We transfected plasmids expressing normal or wild-type (WT) and E50K, R545Q, H26D, and H486R mutant optineurin into a variety of cells such as HeLa, COS-1, retinal pigment epithelial (RPE), and the rat retinal ganglion cell (RGC) line RGC-5, and followed their effects on cell survival by morphologic observation of cells. Expression of optineurin and its mutants was monitored by immunofluorescence staining of cells and by Western blotting. Results The E50K mutant of optineurin, which is associated with the severest phenotype, was seen to selectively induce the death of retinal ganglion cells but not of the other cell lines tested. Neither the wild type cDNA nor the other mutants have any such effect. This cell death induced by E50K OPTN was inhibited by the antioxidants N-acetylcysteine and Trolox. E50K was seen to generate reactive oxygen species (ROS), which were reduced by antioxidants. Coexpression of manganese superoxide dismutase with the E50K mutant abolished ROS production and inhibited cell death. Conclusion E50K optineurin is a gain of function mutant, which has acquired the ability to induce cell death selectively in retinal ganglion cells. This cell death was mediated by oxidative stress. The present findings suggest the possibility of antioxidant use for delaying or controlling some forms of glaucoma. [source] A non-canonical photopigment, melanopsin, is expressed in the differentiating ganglion, horizontal, and bipolar cells of the chicken retinaDEVELOPMENTAL DYNAMICS, Issue 3 2005Sayuri Tomonari Abstract Vertebrate melanopsin is a photopigment in the eye, required for photoentrainment. Melanopsin is more closely related to opsin proteins found in invertebrates, than to the other photo-pigments. Although the invertebrate melanopsin-like protein is localized in rhabdomeric photoreceptors in the invertebrate eye, it has been shown to be expressed in a subset of retinal ganglion cells in the mouse and in horizontal cells in the frog, indicating its diversified expression pattern in vertebrates. Here we show that two types of melanopsin transcripts are expressed in the developing chicken retina. Melanopsin is firstly expressed by a small subset of ganglion cells, and then prominently expressed by horizontal cells and later by bipolar cells in the developing chicken retina. This suggests that a subset of ganglion, horizontal, and bipolar cells in the chicken retina may have rhabdomeric properties in their origins. Developmental Dynamics 234:783,790, 2005. © 2005 Wiley-Liss, Inc. [source] Arachidonic acid as a retrograde signal controlling growth and dynamics of retinotectal arborsDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2008B.H. Leu Abstract In the developing visual system, correlated presynaptic activity between neighboring retinal ganglion cells (RGC) stabilizes retinotopic synapses via a postsynaptic NMDAR (N -methyl- D -aspartate receptor)-dependent mechanism. Blocking NMDARs makes individual axonal arbors larger, which underlies an unsharpened map, and also increases branch turnover, as if a stabilizing factor from the postsynaptic partner is no longer released. Arachidonic acid (AA), a candidate retrograde stabilizing factor, is released by cytoplasmic phospholipase A2 (cPLA2) after Ca2+ entry through activated NMDARs, and can activate presynaptic protein kinase C to phosphorylate various substrates such as GAP43 to regulate cytoskeletal dynamics. To test the role of cPLA2 in the retinotectal system of developing zebrafish, we first used PED6, a fluorescent reporter of cPLA2 activity, to show that 1,3 min of strobe flashes activated tectal cPLA2 by an NMDAR-dependent mechanism. Second, we imaged the dynamic growth of retinal arbors during both local inhibition of tectal cPLA2 by a pharmacological inhibitor, arachidonic tri-fluoromethylketone, and its suppression by antisense oligonucleotides (both injected intraventricularly). Both methods produced larger arbors and faster branch dynamics as occurs with blocking NMDARs. In contrast, intraocular suppression of retinal cPLA2 with large doses of antisense oligos produced none of the effects of tectal cPLA2 inhibition. Finally, if AA is the retrograde messenger, the application of exogenous AA to the tectum should reverse the increased branch turnover caused by blocking either NMDARs or cPLA2. In both cases, intraventricular injection of AA stabilized the overall branch dynamics, bringing rates down below the normal values. The results suggest that AA generated postsynaptically by cPLA2 downstream of Ca2+ entry through NMDARs acts as a retrograde signal to regulate the dynamic growth of retinal arbors. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Neurotrophic rationale in glaucoma: A TrkA agonist, but not NGF or a p75 antagonist, protects retinal ganglion cells in vivoDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2007ZhiHua Shi Abstract Glaucoma is a major cause of vision impairment, which arises from the sustained and progressive apoptosis of retinal ganglion cells (RGC), with ocular hypertension being a major risk or co-morbidity factor. Because RGC death often continues after normalization of ocular hypertension, growth factor-mediated protection of compromised neurons may be useful. However, the therapeutic use of nerve growth factor (NGF) has not proven effective at delaying RGC death in glaucoma. We postulated that one cause for the failure of NGF may be related to its binding to two receptors, TrkA and p75. These receptors have distinct cellular distribution in the retina and in neurons they induce complex and sometimes opposing activities. Here, we show in an in vivo therapeutic model of glaucoma that a selective agonist of the pro-survival TrkA receptor was effective at preventing RGC death. RGC loss was fully prevented by combining the selective agonist of TrkA with intraocular pressure-lowering drugs. In contrast, neither NGF nor an antagonist of the pro-apoptotic p75 receptor protected RGCs. These results further a neurotrophic rationale for glaucoma. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Loss of photic entrainment at low illuminances in rats with acute photoreceptor degenerationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Domitille L. Boudard Abstract In several species, an acute injection of N -methyl- N -nitrosourea (MNU) induces a retinal degeneration characterized principally by a rapid loss of the outer nuclear layer, the other layers remaining structurally intact. It has, however, also been reported that down-regulation of melanopsin gene expression is associated with the degeneration and is detectable soon after injection. Melanopsin is expressed by a small subset of intrinsically photosensitive retinal ganglion cells and plays an important role in circadian behaviour photoentrainment. We injected MNU into Long Evans rats and investigated the ability of animals to entrain to three light/dark cycles of different light intensities (300, 15 and 1 lux). Control animals entrained their locomotor activity rhythms to the three cycles. In contrast, MNU-treated animals could only entrain properly to the 300 lux cycle. For the 15 lux cycle, their phase angle was much altered compared with control animals, and for the 1 lux cycle, MNU-injected animals were unable to photoentrain and exhibited an apparent free-run activity pattern with a period of 24.3 h. Subsequent to behavioural studies the animals were killed and rod, cone, melanopsin expression and melanopsin-expressing cells were quantified. Rod and cone loss was almost complete, melanopsin protein was reduced by 83% and melanopsin-expressing cells were reduced by 37%. Our study provides a comprehensive model of photoreceptor degeneration at the adult stage and a simple and versatile method to investigate the relation between retinal photoreceptors and the circadian system. [source] Characterization and synaptic connectivity of melanopsin-containing ganglion cells in the primate retinaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2007Patricia R. Jusuf Abstract Melanopsin is a photopigment expressed in retinal ganglion cells, which are intrinsically photosensitive and are also involved in retinal circuits arising from rod and cone photoreceptors. This circuitry, however, is poorly understood. Here, we studied the morphology, distribution and synaptic input to melanopsin-containing ganglion cells in a New World monkey, the common marmoset (Callithrix jacchus). The dendrites of melanopsin-containing cells in marmoset stratify either close to the inner nuclear layer (outer stratifying), or close to the ganglion cell layer (inner stratifying). The dendritic fields of outer-stratifying cells tile the retina, with little overlap. However, the dendritic fields of outer-stratifying cells largely overlap with the dendritic fields of inner-stratifying cells. Thus, inner-stratifying and outer-stratifying cells may form functionally independent populations. The synaptic input to melanopsin-containing cells was determined using synaptic markers (antibodies to C-terminal binding protein 2, CtBP2, for presumed bipolar synapses, and antibodies to gephyrin for presumed amacrine synapses). Both outer-stratifying and inner-stratifying cells show colocalized immunoreactive puncta across their entire dendritic tree for both markers. The density of CtBP2 puncta on inner dendrites was about 50% higher than that on outer dendrites. The density of gephyrin puncta was comparable for outer and inner dendrites but higher than the density of CtBP2 puncta. The inner-stratifying cells may receive their input from a type of diffuse bipolar cell (DB6). Our results are consistent with the idea that both outer and inner melanopsin cells receive bipolar and amacrine input across their dendritic tree. [source] Early neural activity and dendritic growth in turtle retinal ganglion cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006Vandana Mehta Abstract Early neural activity, both prenatal spontaneous bursts and early visual experience, is believed to be important for dendritic proliferation and for the maturation of neural circuitry in the developing retina. In this study, we have investigated the possible role of early neural activity in shaping developing turtle retinal ganglion cell (RGC) dendritic arbors. RGCs were back-labelled from the optic nerve with horseradish peroxidase (HRP). Changes in dendritic growth patterns were examined across development and following chronic blockade or modification of spontaneous activity and/or visual experience. Dendrites reach peak proliferation at embryonic stage 25 (S25, one week before hatching), followed by pruning in large field RGCs around the time of hatching. When spontaneous activity is chronically blocked in vivo from early embryonic stages (S22) with curare, a cholinergic nicotinic antagonist, RGC dendritic growth is inhibited. On the other hand, enhancement of spontaneous activity by dark-rearing (Sernagor & Grzywacz (1996)Curr. Biol., 6, 1503,1508) promotes dendritic proliferation in large-field RGCs, an effect that is counteracted by exposure to curare from hatching. We also recorded spontaneous activity from individual RGCs labelled with lucifer yellow (LY). We found a tendency of RGCs with large dendritic fields to be spontaneously more active than small-field cells. From all these observations, we conclude that immature spontaneous activity promotes dendritic growth in developing RGCs. [source] Eph/ephrin expression in the adult rat visual system following localized retinal lesions: localized and transneuronal up-regulation in the retina and superior colliculusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2005J. Rodger Abstract Following unilateral optic nerve section in adult PVG hooded rat, the axon guidance cue ephrin-A2 is up-regulated in caudal but not rostral superior colliculus (SC) and the EphA5 receptor is down-regulated in axotomised retinal ganglion cells (RGCs). Changes occur bilaterally despite the retino-collicular projection being mostly crossed. Here we investigate the dynamics of Eph/ephrin expression using in situ hybridization and semi-quantitative immunohistochemistry after localized retinal lesions. Unilateral krypton laser lesions to dorso-nasal retina ablated contralaterally projecting RGCs (DN group); ventro-temporal lesions ablated contralaterally and ipsilaterally projecting RGCs (VT group). Lesions of the entire retina served as controls (Total group). Results are compared to normal animals in which tectal ephrin-A2 and retinal EphA5 are expressed, respectively, as shallow ascending rostro-caudal and naso-temporal gradients. In both SCs of DN and Total groups, tectal ephrin-A2 was up-regulated caudally; in the VT group, expression remained normal bilaterally. Unilateral collicular ablation indicated that bilateral changes in ephrin-A2 expression are mediated via intercollicular pathways. EphA5 expression in the VT group was elevated in the intact nasal region of experimental retinae. For each experimental group, EphA5 expression was also elevated in nasal retina of the opposite eye, resulting in uniform expression across the naso-temporal axis. Up-regulation of ephrin-A2 in caudal, but not rostral, SC suggests the enhancement of developmental positional information as a result of injury. Bilateral increases in retinal EphA5 expression demonstrate that signals for up-regulation operate interocularly. The study demonstrates that signals regulating guidance cue expression are both localized and relayed transneuronally. [source] Synaptic contacts between an identified type of ON cone bipolar cell and ganglion cells in the mouse retinaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2005Bin Lin Abstract We surveyed the potential contacts between an identified type of bipolar cell and retinal ganglion cells in the mouse. By crossing two existing mouse strains (line 357 and line GFP-M), we created a double transgenic strain in which GFP is expressed by all members of a single type of ON cone bipolar cell and a sparse, mixed population of retinal ganglion cells. The GFP-expressing bipolar cells appear to be those termed CB4a of Pignatelli & Strettoi [(2004) J. Comp. Neurol., 476, 254,266] and type 7 of Ghosh et al. [(2004) J. Comp. Neurol., 469, 70,82 and J. Comp. Neurol., 476, 202,203]. The labelled ganglion cells include examples of most or all types of ganglion cells present in the mouse. By studying the juxtaposition of their processes in three dimensions, we could learn which ganglion cell types are potential synaptic targets of the line 357 bipolar cell. Of 12 ganglion cell types observed, 10 types could be definitively ruled out as major synaptic targets of the line 357 bipolar cells. One type of monostratified ganglion cell and one bistratified cell tightly cofasciculate with axon terminals of the line 357 bipolar cells. Double labelling for kinesin II demonstrates colocalization of bipolar cell ribbons at the sites of contact between these two types of ganglion cell and the line 357 bipolar cells. [source] Postnatal innervation of the rat superior colliculus by axons of late-born retinal ganglion cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2002Elizabeth J. Dallimore Abstract Rat retinal ganglion cells (RGCs) are generated between embryonic day (E) 13 and E19. Retinal axons first reach the superior colliculus at E16/16.5 but the time of arrival of axons from late-born RGCs is unknown. This study examined (i) whether there is a correlation between RGC genesis and the timing of retinotectal innervation and (ii) when axons of late-born RGCs reach the superior colliculus. Pregnant Wistar rats were injected intraperitoneally with bromodeoxyuridine (BrdU) on E16, E18 or E19. Pups from these litters received unilateral superior colliculus injections of fluorogold (FG) at ages between postnatal (P) day P0 and P6, and were perfused 1,2 days later. RGCs in 3 rats from each BrdU litter were labelled in adulthood by placing FG onto transected optic nerve. Retinas were cryosectioned and the number of FG, BrdU and double-labelled (FG+/BrdU+) RGCs quantified. In the E16 group, the proportion of FG-labelled RGCs that were BrdU+ did not vary with age, indicating that axons from these cells had reached the superior colliculus by P0/P1. In contrast, for the smaller cohorts of RGCs born on E18 or E19, the proportion of BrdU+ cells that were FG+ increased significantly after birth; axons from most RGCs born on E19 were not retrogradely FG-labelled until P4/P5. Thus there is a correlation between birthdate and innervation in rat retinotectal pathways. Furthermore, compared to the earliest born RGCs, axons from late-born RGCs take about three times longer to reach the superior colliculus. Later-arriving axons presumably encounter comparatively different growth terrains en route and eventually innervate more differentiated target structures. [source] Immune-related mechanisms participating in resistance and susceptibility to glutamate toxicityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002Hadas Schori Abstract Glutamate is an essential neurotransmitter in the CNS. However, at abnormally high concentrations it becomes cytotoxic. Recent studies in our laboratory showed that glutamate evokes T cell-mediated protective mechanisms. The aim of the present study was to examine the nature of the glutamate receptors and signalling pathways that participate in immune protection against glutamate toxicity. We show, using the mouse visual system, that glutamate-induced toxicity is strain dependent, not only with respect to the amount of neuronal loss it causes, but also in the pathways it activates. In strains that are genetically endowed with the ability to manifest a T cell-dependent neuroprotective response to glutamate insult, neuronal losses due to glutamate toxicity were relatively small, and treatment with NMDA-receptor antagonist worsened the outcome of exposure to glutamate. In contrast, in mice devoid of T cell-dependent endogenous protection, NMDA receptor antagonist reduced the glutamate-induced neuronal loss. In all strains, blockage of the AMPA/KA receptor was beneficial. Pharmacological (with ,2 -adrenoceptor agonist) or molecular intervention (using either mice overexpressing Bcl-2, or DAP-kinase knockout mice) protected retinal ganglion cells from glutamate toxicity but not from the toxicity of NMDA. The results suggest that glutamate-induced neuronal toxicity involves multiple glutamate receptors, the types and relative contributions of which, vary among strains. We suggest that a multifactorial protection, based on an immune mechanism independent of the specific pathway through which glutamate exerts its toxicity, is likely to be a safer, more comprehensive, and hence more effective strategy for neuroprotection. It might suggest that, because of individual differences, the pharmacological use of NMDA-antagonist for neuroprotective purposes might have an adverse effect, even if the affinity is low. [source] Distribution of glycine receptor subunits on primate retinal ganglion cells: a quantitative analysisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2000Bin Lin Abstract This study investigates the distribution of inhibitory neurotransmitter receptors on sensory neurons. Ganglion cells in the retina of a New World monkey, the common marmoset Callithrix jacchus, were injected with Lucifer yellow and Neurobiotin and subsequently processed with antibodies against one (,1), or against all subunits, of the glycine receptor, or against the anchoring protein gephyrin. Immunoreactive (IR) puncta representing glycine receptor or gephyrin clusters were found on the proximal and the distal dendrites of all ganglion cell types investigated. For both parasol and midget cells, the density of receptor clusters was greater on distal than proximal dendrites for all antibodies tested. In parasol cells the average density for the ,1 subunit of the glycine receptor was 0.087 IR puncta/µm of dendrite, and for all subunits it was 0.119 IR puncta/µm of dendrite. Thus, the majority of glycine receptors on parasol cells contain the ,1 subunit. For parasol cells, we estimated an average of 1.5 glycinergic synapses/100 µm2 dendritic membrane on proximal dendrites and about 9.4 glycinergic synapses/100 µm2 on distal dendrites. The segregation of receptors to the distal dendrites appears to be a common feature of inhibitory neurotransmitter input to parasol and midget cells, and might be associated with the receptive field surround mechanism. [source] Glaucomatous optic nerve injury involves early astrocyte reactivity and late oligodendrocyte lossGLIA, Issue 7 2010Janice L. Son Abstract Glaucoma, a neurodegenerative disease affecting retinal ganglion cells (RGC), is a leading cause of blindness. Since gliosis is common in neurodegenerative disorders, it is important to describe the changes occurring in various glial populations in glaucoma animal models in relation to axon loss, as only changes that occur early are likely to be useful therapeutic targets. Here, we describe changes occurring in glia within the myelinated portion of the optic nerve (ON) in both DBA/2J mice and in a rat ocular hypertension model. In both glaucoma animal models, we found only a modest loss of oligodendrocytes that occurred after axons had already degenerated. In DBA/2J mice there was proliferation of oligodendrocyte precursor cells (OPCs) and new oligodendrocyte generation. Activation of microglia was detected only in highly degenerated DBA/2J ONs. In contrast, a large increase in astrocyte reactivity occurred early in both animal models. These results are consistent with astrocytes playing a prominent role in regulating axon loss in glaucoma. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||