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PubMed1995

[Dextromethorphan maintains the function of the detached retina].

In order to evaluate the effect of dextromethorphan (DEX), an antagonist of N-methyl-D-aspartate receptors, on ischemic damage in the detached retina, transretinal electrical responses (trans-retinal electroretinogram: TR-ERG) to photic stimulation were recorded from the detached retina of rabbit eyes in vitro. In experiment 1, 0.1 ml of 0.1% DEX was injected into the subretinal space to produce retinal detachment (RD) of 8 mm diameter (DEX group). For the control, the same volume of Hanks' solution was injected instead of DEX (control group). In experiment 2, 0.1 ml of 0.1% DEX was dropped onto retina, and RD was produced by injecting 0.1 ml of Hanks' solution into the subretinal space (DEX group). For the control, the same volume of saline was dropped onto the retina instead of DEX (control group). In experiment 1, the averaged b-wave amplitude of the TR-ERG decreased significantly (p < 0.01) at 3 hrs after RD in the control group, but it was almost stable and did not show significant decrease in the DEX group. In experiment 2, the averaged b-wave amplitude of the ERG decreased significantly (p < 0.05) at 2 hrs after the RD in the control, but showed no significant decrease even at 3 hrs after RD in the DEX group. These results indicate that DEX injected into the subretinal space and dropped onto the retina before producing RD may reduce ischemic damage in the detached retina.

Animals↗
PubMed1996

Radial distribution of tocopherols in rhesus monkey retina and retinal pigment epithelium-choroid.

PURPOSE: To map vitamin E as a function of distance from the foveal center in the primate retina and retinal pigment epithelium (RPE)-choroid. METHODS: Eyecups from rhesus monkeys were dissected with circular trephines so that the innermost disc, centered on the fovea, was in the center of a series of concentric rings. Two different types of dissection were performed. For one type, the authors used circular trephines with diameters of 1, 4, 8, and 10 mm (1,4-D), whereas for the other type the diameters were 2, 5, 8, and sometimes 10 mm (2,5-D). When possible, the neural retina was separated from the RPE-choroid. Tissues were analyzed for vitamin E, retinyl palmitate, and protein. RESULTS: Surface area, volume, and protein were used as indexes of the amount of tissue analyzed. Distributions of vitamin E in neural retina were dependent on the tissue metric used and type of dissection performed. However, regardless of the tissue metric used, the central 1-mm disc of the 1,4-D was, on average, higher in vitamin E content than was the central 2-mm disc of the 2,5-D. This was particularly true when volume was the tissue metric. From the average values of vitamin E in a series of concentric discs, a composite plot of the vitamin E concentration in the neural retina was generated that took into consideration both types of dissection. That plot displayed a local maximum in the fovea and then precipitously declined to a minimum in the region between 0.5 and 1.0 mm eccentricity (near the foveal crest); at greater eccentricities, the vitamin E concentration rose to a value similar to that in the fovea, i.e., the composite plot indicated that vitamin E has a V-shaped distribution in the central neural retina. Vitamin E distribution in the RPE-choroid, with surface area as the tissue metric, also was measured. For this tissue, the foveal region displayed a local maximum. CONCLUSIONS: By combining the results of two different types of dissection, the authors found that in the neural retina, vitamin E displayed a minimum near the foveal crest. This minimum correlated anatomically with the site at which areolar (geographic) atrophy frequently occurs in retinal pigment epithelial cells in the human disease, age-related macular degeneration.

Animals↗
PubMed1996

Temporal expression of rod and cone opsins in embryonic goldfish retina predicts the spatial organization of the cone mosaic.

PURPOSE: Cone photoreceptors in teleost fish retina are organized into a precise, crystalline mosaic in which the four spectral subtypes have a consistent position relative to each other. The objective of the current study was to describe the spatial and temporal progression of photoreceptor differentiation in the embryonic goldfish retina to understand how the retinal cone mosaic might be produced. METHODS: To identify developing photoreceptors when they first begin to express a specific opsin, the authors used in situ hybridization with cRNA probes generated from cDNA for rod opsin and red, green, blue, and ultraviolet cone opsins from goldfish (Carassius auratus). RESULTS: In the retina, rod opsin was expressed first, and it was restricted to a small patch of regularly spaced, precocious rods located near the ventronasal edge of the retina, close to the choroid fissure. The patch enlarged by recruitment of additional rods in a circular path, moving from ventral to nasal to dorsal to temporal retina. Expression of cone opsins began approximately 10 hours after rod opsin was first expressed, and differentiation of cone photoreceptors followed the spatial pattern laid down by the early rods. The temporal order of onset of cone opsin expression was red, then green, then blue, then ultraviolet. When rod and red cone opsin probes were combined, the number of labeled cells was additive, suggesting that these two opsins are expressed in separate populations of photoreceptors. CONCLUSIONS: The onset of opsin expression in goldfish retina follows a highly ordered spatio-temporal pattern. Early differentiation and regular spacing of the precocious rods was unexpected and suggested that they may play a role in cone mosaic patterning. The order of subsequent cone opsin expression was related to the relative positions of cone subtype in the mosaic, suggesting the possibility that inductive interactions among developing photoreceptors may be responsible for patterning the cone mosaic array.

Animals↗
PubMed1996

Expression and downregulation of the GABAergic phenotype in explants of cultured rabbit retina.

PURPOSE: To study the morphologic and neurochemical development of the rabbit retina in explant culture. METHODS: Explants of retina from newborn rabbits were cultured in defined medium in the absence of serum or soluble growth factors. The morphology of the explant and the neurochemical development of the GABAergic system were examined by light microscopy, autoradiography, and immunohistochemistry for 7 days and compared to those of the postnatal rabbit retina in vivo. RESULTS: Cultured explants from newborn rabbit retina develop and maintain well-defined plexiform and cellular layers up to 7 days. Exogenous 3H-gamma-aminobutyric acid (GABA) and antibodies against GABA labeled a population of horizontal, amacrine and displaced amacrine cells in the ganglion cell layer during the first 3 days in culture. After 4 days in culture, the extent of uptake and immunolabeling was diminished among all three cell types, but labeled horizontal cells were markedly rare. At 7 days in culture, uptake and GABA-like immunoreactivity could not be detected in horizontal cells, but antibodies to calbindin-D reacted with horizontal and amacrine cells in the appropriate retinal layers. Peanut agglutinin lectin binding studies revealed a mosaic of cone photoreceptor inner segments indistinguishable from that of neonatal retina in vivo. CONCLUSIONS: The experiments show that the maturation of cellular layers and the developmental expression of the GABAergic phenotype can be observed in retinal explants cultured under chemically defined conditions. Histochemical evidence is presented that indicates cultured explants of newborn rabbit retinas express markers of the GABAergic phenotype in a manner consistent with that observed in vivo. The authors show that horizontal cells continue to survive in culture after the diminution in GABA immunoreactivity.

Animals↗
PubMed1996

Cone-associated c-fos gene expression in the light-damaged rat retina.

PURPOSE: To examine whether light-controlled c-fos gene expression is mediated by a cone specific pathway in the rat retina. METHODS: To produce a cone-rich retina, rats were placed under continuous lighting for 21 days. The illuminance in the cages ranged from 1200 to 2000 lux. The presence of cones was determined by peanut agglutinin and rods by the monoclonal antibody 1-E7. The presence of c-fos transcripts in the retinas was analyzed by in situ hybridization using single-stranded RNA probes. RESULTS: After long-term exposure to continuous light, the 1-E7 immunoreactivity was not detected in the outer nuclear layer. The cone photoreceptors and cells in the ganglion cell (GCL) and inner nuclear layers (INL) survived. In normal retinas, there was strong hybridization for c-fos expression in the GCL and the INL 30 minutes after the onset of the light cycle. Light-damaged retinas also showed hybridization in the GCL but not in the INL under the same light regime. CONCLUSIONS: These results suggest that c-fos gene expression can be controlled through a cone specific pathway in the retina.

Animals↗
PubMed1996

Glial fibrillary acidic protein expression in the developing human retina.

We have studied the expression of glial fibrillary acidic protein(GFAP), an astrocyte specific protein in the normal developing human retina using anti-GFAP antibody. GFAP positive cells were first detected at 24 gestational weeks(GW) in the nerve fiber and ganglion cell layers in the vicinity of the optic disc. Over subsequent weeks, GFAP positive cells covered larger regions of the retina. Some of the processes of these cells terminated in sucker like end-feet upon blood vessels of the nerve fiber layer. A second population of GFAP positive cells existed as perivascular glia in the nerve fiber layer in the early stage of fetal development. In the adult retina perivascular glia were found on vessels throughout the nerve fiber and in the inner portion of the inner plexiform layers. Staining of Müller cells end-feet was obtained only in the adult retina. These results support the views that in the human retina, GFAP positive cells first appear at 24 GW in the region near the optic disc, covering the whole retina at subsequent ages.

Adolescent↗
PubMed1996

Modification of vitronectin by advanced glycation alters functional properties in vitro and in the diabetic retina.

Early diabetic retinopathy is characterized by areas of acellular capillaries and the accumulation of advanced glycation end products (AGE). Endothelial cell maintenance, growth, and migration is regulated by a complex system involving the partitioning of growth factors between extracellular matrix-bound proteoglycans and cells, as well as by the activation and control of pericellular proteolysis. Using specific antibodies, we compared the immunolocalization of the vascular heparan sulfate proteoglycan (HSPG)-binding protein vitronectin (VN), HSPG, basic fibroblast growth factor, and collagen type 1 in retinae prepared from 11-month-old diabetic and nondiabetic Wistar rats. In normal rats, VN immunostaining was prominent in vascularized parts of the inner retina and colocalized with HSPG, which itself showed costaining with basic fibroblast growth factor in the extracellular matrix, vascular walls, and the inner limiting membrane. In contrast, the recognition of VN, HSPG, and basic fibroblast growth factor in diabetic retinae was greatly reduced in the inner limiting membrane and the extracellular matrix, where increased immunoreactive AGE colocalizing with VN were detectable. Capillary labeling of retinal vessel walls for plasminogen activator inhibitor-1 was moderate in both normal and diabetic retinae. AGE-VN was demonstrated in tissue extracts from retina by immunoprecipitation and Western blotting and presented a similar increase of AGE-related immunoreactivity compared with AGE-VN generated in vitro. AGE-VN in vitro had lost its native conformation, yielded high Mr SDS-resistant products, and was resistant to proteolysis because of modification of about 30% of lysines. Because binding of glycosaminoglycans, as well as interaction of type I collagen and the morphoregulatory proteins osteonectin and tenascin with AGE-VN, were reduced to at least 50% of control, alteration of basic residues in the heparin-binding domain of VN is plausible. In comparison to nonmodified VN, AGE-VN exhibited reduced cell attachment-promoting activity. Together, these in vitro results suggest that AGE-VN found in vivo is related to morphologic and functional changes in the diabetic retina and may contribute to the genesis of acellular capillaries in early diabetic retinopathy.

Animals↗
PubMed1995

Antioxidant effect of a Ginkgo biloba extract (EGb 761) on the retina.

Several investigations have recently shown that the retina is very sensitive to oxygenated free radicals (O2-, OH.) at the origin of the membrane phospholipids peroxidation. Peroxy radical (ROO.) release is responsible for the induction of electrophysiological disturbances leading to retinopathy development. As Ginkgo biloba extract (EGb 761, IPSEN, France) was reported to scavenge primary (O2-, OH.) and secondary (ROO.) free radicals, we evaluated its antioxidant effect on retinas of albino rats submitted to different types of aggressors. On isolated rat retina, EGb 761 given orally significantly protected against lipoperoxidation induced by a mixture of ferrous sulfate and sodium ascorbate added to the perfusion solution. With EGb 761, the decrease of the b-wave ERG amplitude was less pronounced and the retina survival was increased. EGb 761 was also effective against ischaemia-reperfusion disorders due to occlusion of the central retinal artery or by intraocular hypertony. Like other antioxidants such as superoxide dismutase tested on these models, EGb 761 significantly attenuated, according to a dose-response effect, the free-radical injury. EGb 761 reduces the decrease of the b-wave amplitude, the oedema, necrosis and ion homeostasis disturbances. Xenobiotics are also responsible for the retinotoxicity partly due to free radicals and PAF release. We noted an EGb 761 dose-dependent protective effect against acute and chronic chloroquine toxicity to the retina. The deleterious effect of chloroquine was characterized by a delayed b-wave and an asymmetry of the signal with slow declining b-wave. After EGb 761 treatment, the ERG aspect was partially normal. In conclusion, EGb 761, by its general free-radical scavenger properties, is an antioxidant that inhibits or reduces the functional and morphological retina impairments observed after lipoperoxide release.

Animals↗
PubMed1996

Synaptic development in macaque monkey retina and its implications for other developmental sequences.

New and existing data are presented regarding synaptic development in primate retina with the aims to identify the sequence in which individual cell types form synapses in the inner plexiform (IPL) and outer plexiform (OPL) layers; to compare synaptic development sequences in cone-dominated fovea and rod-dominated peripheral retina; to compare synaptic formation with other aspects of cell differentiation; and to explore the possible roles for synapses in development. The first synapses are formed in the foveal IPL by bipolar axons at fetal day 55, followed at fetal day 60 by cone ribbon synapses. Amacrine synapses in the foveal IPL only appear in significant numbers at fetal day 88. In peripheral retina amacrine synapses are formed at fetal day 78, bipolar at 99, and photoreceptors at 105. Thus, the fovea forms the first synapses and the IPL matures before the OPL across the retina, but the fovea has a different bipolar/amacrine sequence than peripheral retina. Foveal synapses are present before many photoreceptor-specific proteins such as opsins can be detected, suggesting that some phenotypic information from the inner retina could influence the direction of photoreceptor development. The early synaptic development in the fovea may serve an important mechanical role during subsequent cell migrations that form the mature foveal pit and tightly packed cone foveola.

Animals↗
PubMed1997

Ultrastructural analysis of interleukin-1 beta-induced leukocyte recruitment to the rat retina.

PURPOSE: To examine, by ultrastructural analysis, the effect of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) on the integrity of the rat retina and blood-retinal barrier (BRB) and to investigate the site of barrier leakage and the path of leukocyte infiltration into the retina. METHODS: After a single injection of IL-1 beta into the vitreous of the Lewis rat, leukocyte recruitment and retinal disease was assessed immediately and at frequent periods up to 14 days after injection by light and electron microscopy and by immunohistochemistry. The integrity of the BRB and the site of barrier disruption were evaluated using the large molecular weight tracer horseradish peroxidase. The phenotype of recruited leukocytes to the retina was assessed by ultrastructural morphology and immunohistochemistry. RESULTS: At 4 hours after the intravitreal administration of IL-1 beta, leukocytes were observed infiltrating the retina. Leukocyte infiltration increased gradually and peaked between 24 and 48 hours after injection. Associated with this infiltrate were edema and fibrin leakage, indicative of a breakdown in the BRB. This was confirmed by the demonstration of horseradish peroxidase extravasation across the retinal vascular bed, with leakage of the tracer through disrupted endothelial tight junctions. Using immunohistochemical and morphologic criteria, the majority of infiltrating cells were identified as monocytes-macrophages and neutrophils; occasionally, T cells were found. Ultrastructural analysis showed that the majority of cells entered the retina by migrating through retinal endothelial cells and that there was a smaller contribution from the ciliary body. CONCLUSIONS: The administration of IL-1 beta to the vitreous of the Lewis rat causes an acute, reversible retinal inflammatory response that is accompanied by breakdown of the vascular BRB. Interleukin-1 beta induces the recruitment of mononuclear and polymorphonuclear leukocytes that enter the retina predominantly through the retinal vasculature and that appear to migrate through retinal endothelial cells. These results suggest that IL-1 beta may be an important factor in the pathogenesis of human retinal inflammation.

Animals↗
PubMed1997

Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy.

PURPOSE: To determine whether vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which have been implicated in the development of retinal and choroidal neovascularization, are present in the retinas and optic nerves of patients with diabetes before proliferative retinopathy appears. METHODS: Light microscopic immunocytochemistry using antibodies to VEGF, bFGF, vimentin, glial fibrillary acidic protein (GFAP), and factor VIII on frozen sections from eyes of patients with diabetes without proliferative retinopathy, eyes of patients without diabetes and without known ocular disease, and eyes with disciform age-related macular degeneration (ARMD). Retinal vascular digest preparations to evaluate microvascular abnormalities. RESULTS: Based on morphology and on GFAP and vimentin immunopositivity, retinas from all subjects with diabetes immunostained strongly to VEGF in elongated processes that appeared to be Müller cells. Glial cells within septa surrounding axons in the anterior optic nerve also immunostained for VEGF, as did endothelial cells of some posterior retinal blood vessels and some retinal pigment epithelial cells. Retinas from eyes with disciform ARMD immunostained for VEGF, though less extensively than did those of subjects with diabetes. Retinas and optic nerves from subjects without ocular disease were VEGF negative. Basic fibroblast growth factor was expressed minimally in the inner retinal layers of subjects with and without diabetes, but it was substantial in the photoreceptor layer of all eyes. Vascular endothelial growth factor immunopositivity was present in eyes with no, or little, retinal vascular anatomic abnormality in digest preparations. CONCLUSIONS: Vascular endothelial growth factor expression precedes retinal neovascularization in the retinas and the optic nerves of humans with diabetes. Its localization to glial cells of the inner retina and the anterior optic nerve suggests a relationship to neovascularization in these sites. That VEGF immunopositivity may occur when there is no anatomic evidence of retinal nonperfusion and little likelihood of retinal neovascularization suggests the possibility that ischemia may not be the sole stimulus for VEGF expression.

Aged↗
PubMed1997

Expression of major histocompatibility complex molecules in rodent retina. Immunohistochemical study.

PURPOSE: In Lewis rats, S-antigen-induced intraocular inflammation, which occurs initially in the retina, is mediated by T cells requiring major histocompatibility complex (MHC)-restricted antigen presentation. In such organ-specific inflammation, antigen presentation may take place at the site of the initial inflammatory response. In the present study an attempt was made to determine the presence of the putative antigen-presenting cells in the retina of rats. METHODS: Six bone marrow chimeras were constructed by transferring 50 x 10(6) donor [Lewis x Brown Norway, (LBN) F1] bone marrow cells into lethally irradiated Brown Norway rats. Three chimeras, 3 Lewis, and 2 Brown Norway rats each received intravenous injections of gamma interferon (IFN-gamma) at a dose of 2 x 10(5) U/rat, 48 and 24 hours before enucleation of the globes. Enucleated globes from the 3 remaining untreated chimeras, 21 additional Lewis rats, and 6 Brown Norway rats served as controls. Retinas from all globes were prepared for either wholemount or cryosectioning and were stained using various primary antibodies, including anti-Lewis MHC class II (OX3), anti-rat MHC class II (OX6), anti-Lewis MHC class I (II-69), anti-rat MHC class I (OX18), anti-macrophage complement receptor 3 (OX42), anti-monocytes/macrophages (ED1, ED2, and ED3), and anti-glial fibrillary acidic protein (GFAP). Fluorescein-conjugated goat anti-mouse and rhodamine-conjugated anti-rabbit immunoglobulins were used to detect the monoclonal or polyclonal antibodies, respectively. All the specimens were examined under Zeiss confocal laser scanning microscopy. The positively stained cells were counted for quantitative analysis. RESULTS: Major histocompatibility complex class II (OX6)-positive cells were demonstrated in the wholemount retinas of IFN-gamma-untreated chimeras, Lewis, and Brown Norway rats. These cells showed a dendritic morphology and increased significantly in number in IFN-gamma-treated Lewis and Brown Norway rats. Expression of Lewis-specific class I (II-69) and class II (OX3) molecules was detected in a few perivascular cells in the retina of chimeric rats treated with IFN-gamma. Most dendritic cells in the retina expressed the macrophage markers, ED1 and OX42, without IFN-gamma treatment. However, vascular endothelia, retinal pigment epithelia, Müller cells, and astrocytes stained neither by Class II molecules nor by macrophage markers. The vascular endothelium and retinal pigment epithelium was found to express constitutively class I molecules (OX18). CONCLUSIONS: A subpopulation of retinal microglia can express MHC class II molecules. Only a few of these are derived from bone marrow. Retinal microglial cells, particularly those derived from bone marrow, may participate in antigen presentation and the subsequent development of retinitis, as seen in S-antigen-induced experimental autoimmune uveoretinitis.

Animals↗
PubMed1997

Retinoic acid synthesis in the developing chick retina.

The transcriptional activator retinoic acid (RA) has been shown to influence the early patterning of the vertebrate eye. Models for the establishment of the retinofugal projection postulate gradients of cell-surface markers across the retinal surface that are expressed by ganglion cells and mediate the correct connection of fibers within central target fields. Spatial asymmetries of RA and RA-producing enzymes, as have been found in the eyes of mice and zebrafish, could induce the required asymmetry in gene expression. Here we exploited the large size of the retina of the embryonic chick to analyze the spatial and temporal characteristics of the RA system by HPLC in combination with a reporter cell assay. As in other embryonic vertebrates, the chick retina was found to contain different RA-generating enzymes segregated along the dorsoventral axis. The major RA isomer in both dorsal and ventral retina was all-trans RA, and no 9-cis RA could be detected. This excludes a difference in production of these two isomers as an explanation for the expression of different RA-generating enzymes. At developmental stages embryonic days (E) 4 and 5, the ventral retina contained higher all-trans RA levels than the dorsal retina. After E8, however, the difference disappeared, and in embryos at E9 and older the RA concentration was slightly higher in dorsal than ventral retina.

Aldehyde Dehydrogenase↗
PubMed1997

Modulation of major histocompatibility complex class II expression in retinas with age-related macular degeneration.

PURPOSE: To investigate antigenic and morphologic features of microglial and vascular elements in the neural retina associated with age-related macular degeneration (ARMD) compared with those features in age-matched normal and young adult retinas. METHODS: Adult eyes (n = 97) were classified histopathologically into normal and ARMD-associated groups. Peroxidase imunohistochemical examination of retinal flatmounts was used to visualize major histocompatibility complex class II (MHC-II) immunoreactivity; the intensity and distribution of labeling were quantified by image analysis. In histochemical investigation, reduced nicotinamide-adenine dinucleotide phosphate diaphorase and glial fibrillary acidic protein or MHC-II double labeling were used to detect vascular changes in some preparations. RESULTS: An increase in the proportion of the retina (percentage of total area) expressing MHC-II immunoreactivity was observed in age-matched retinas compared with that seen in normal retinas. A significant increase (P < 0.05) in the percentage of area immunoreactive for MHC-II was observed, primarily on vascular elements, in retinas with incipient ARMD compared with the area affected in the age-matched group. Increased MHC-II immunoreactivity on vessels in the normal-aged group observed with confocal microscopy was associated with irregularities in the organization of astrocytes. Hypertrophy of retinal microglia was also apparent, although the intensity of microglial MHC-II immunoreactivity was not significantly different between groups. CONCLUSIONS: The results indicate that an increase in MHC-II immunoreactivity on retinal vascular elements is associated with normal aging. A further increase in MHC-II immunoreactivity on vascular elements and morphologic changes in microglia was associated with incipient ARMD. Immunologic responses in neural retinal microglia and vascular elements appear to be related to early pathogenetic changes in retinal pigment epithelium pigmentation and drusen formation.

Adult↗
PubMed1997

Subcellular concentration of beta-dystroglycan in photoreceptors and glial cells of the chick retina.

Mutations in the dystrophin-glycoprotein complex cause muscle degeneration and dysfunctions in the central nervous system, including an impaired synaptic transmission in the outer plexiform layer (OPL) of the retina. To investigate the basis for this ocular phenotype, we analyzed the distribution of beta-dystroglycan, a central member of the dystrophin-glycoprotein complex, in the chick retina by using the 43DAG/8D5 monoclonal antibody. This antibody reacted specifically with chick beta-dystroglycan, as indicated by its staining of the neuromuscular junction, and its reactivity with a single 43-kilodalton band in Western blots. In the retina, beta-dystroglycan was highly concentrated in the OPL and at the vitreal border of the retina, around the inner limiting membrane. Mechanically isolated and flat-mounted inner limiting membranes were stained by the anti-beta-dystroglycan antibody, and this immunoreactivity could be extracted by detergent, indicating that beta-dystroglycan is associated with membranous structures bound to the basal lamina. Consistently, electron microscopy showed a concentration of beta-dystroglycan in the endfeet of Müller glial cells exclusively in the region of direct contact to the inner limiting membrane. In the OPL, beta-dystroglycan immunoreactivity was concentrated in the distal extensions of rod and cone terminals protruding into the outer plexiform layer. There, beta-dystroglycan codistributed with the alpha1beta subunit of the N-type voltage-gated calcium channel. By contrast to previous reports, we did not detect beta-dystroglycan directly associated with the synaptic regions of conventional or ribbon synapses of the retina. These results show that in the retina beta-dystroglycan is exclusively expressed by photoreceptors and glial cells and that beta-dystroglycan is highly concentrated in subcellular regions of glial cell endfeet and photoreceptor terminals. Moreover, the colocalization of beta-dystroglycan with N-type calcium channels in the outer plexiform layer indicates that both proteins might be part of a macromolecular complex.

Agrin↗
PubMed1998

Axonal versus dendritic outgrowth is differentially affected by radial glia in discrete layers of the retina.

Formation of neural cell polarity defined by oriented extension of axons and dendrites is a crucial event during the development of the nervous system. Ganglion cells of the chicken retina extend axons exclusively into the inner retina, whereas their dendrites grow into the outer retina. To analyze guidance cues for specific neurite extension, novel in vitro systems were established. Ganglion cells were purified by enzymatically facilitated detachment of the ganglion cell layer. A newly developed retrograde labeling technique and the expression analysis of the cell type-specific 2A1 antigen were used to monitor ganglion cell purification. In highly purified ganglion cells explanted onto retinal cryosections (cryoculture), axon formation was induced when the cells were positioned on the inner retina. In contrast, on outer layers of the developing retina dendritic outgrowth was prevalent. Because radial glia have been demonstrated to be instructive in neuritogenesis, distinct glial cell compartments located in inner and outer retina, respectively, were isolated for functional assays. Glial end feet were purified by a physical detachment technique. Glial somata were purified by complement mediated cytolysis of all nonglial cells. When ganglion cells were cultured on different glial compartments, axon formation occurred on end feet but not on glial somata. In striking contrast, on glial somata dendrites were formed. The data support the notion that ganglion cell polarity is affected by the retinal microenvironment, which in turn is possibly influenced by radial glia, being themselves polarized.

Animals↗
PubMed1998

Ganglion cell loss in RCS rat retina: a result of compression of axons by contracting intraretinal vessels linked to the pigment epithelium.

In the dystrophic Royal College of Surgeons (RCS) rat retina, there is a progressive loss of photoreceptors. As a result, the retinal circulation becomes apposed to the retinal pigment epithelium (RPE) and neovascular formations develop. RPE and inner nuclear layer cells migrate along these vessels towards the retinal ganglion cell (RGC) layer. The retinal layers gradually become disrupted, and some of the RGC axon bundles involute into the retina. These bundles are always associated with blood vessels, and there is evidence of axon damage where they juxtapose. In wholemount preparations of dystrophic retinae (> or =6 months of age), abrupt changes are observed in the trajectory of RGC axon bundles, where they are crossed by circumferential vessels. Degenerative profiles can be seen at these locations. Visualisation of RGCs with Fluoro-gold shows wedge-shaped sectors in the dystrophic retina devoid of labelling, initially in the ventral retina but later spreading dorsally. It is hypothesised that the vessels supplying the neovascular formations contract and pull surface vessels into the retina, thus displacing any axon bundles that lie beneath them into the inner plexiform layer. The contractility may be an intrinsic property of the vessels or it may be conferred by the cells migrating along them. Axonal transport becomes blocked at the points of tension, thereby causing retrograde degeneration of the parent RGCs. Because RGC loss is also a feature of human retinitis pigmentosa, the RCS rat may provide a model to test interventions devised to prevent such loss following photoreceptor degeneration. This model also may be useful for testing methods designed to control blood vessel and matrix formation.

Animals↗
PubMed1998

Direct participation of starburst amacrine cells in spontaneous rhythmic activities in the developing mammalian retina.

Spontaneous, rhythmic waves of excitation in the developing mammalian retina play a critical role in the formation of precise neuronal connectivity in the visual system. However, it is not known what circuits in the retina are responsible for the production of these waves. Using patch-clamp recordings in the whole-mount neonatal rabbit retina, this study reports that the displaced starburst amacrine cell, a unique cholinergic interneuron in the ganglion cell layer of the retina, undergoes rhythmic bursts of membrane depolarization with a frequency and duration similar to those of spontaneous retinal waves. Simultaneous patch-clamp recordings from pairs of neighboring starburst and ganglion cells show that the rhythmic activity in starburst cells is closely correlated with that in ganglion cells, and that the excitation in both cell types is most likely driven by synaptic input. However, in contrast to ganglion cells, displaced starburst cells usually do not generate spontaneous somatic action potentials. Instead, they seem to use subthreshold potentials (at least at the soma) to mediate the rhythmic excitation. The results suggest that acetylcholine is likely released rhythmically in the developing retina. Thus, starburst amacrine cells form the first identified network of retinal interneurons that directly participate in spontaneous rhythmic activities in the developing retina.

Action Potentials↗