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PubMed2005

Distinct patterns of expression of the RB gene family in mouse and human retina.

Although RB1 function is disrupted in the majority of human cancers, an undefined cell of developing human retina is uniquely sensitive to cancer induction when the RB1 tumor suppressor gene is lost. Murine retinoblastoma is initiated only when two of the RB family of genes, RB1 and p107 or p130, are inactivated. Although whole embryonic retina shows RB family gene expression by several techniques, when E14 developing retina was depleted of the earliest differentiating cells, ganglion cells, the remaining proliferating murine embryonic retinal progenitor cells clearly did not express RB1 or p130, while the longer splice form of p107 was expressed. Each retinal cell type expressed some member of the RB family at some stage of differentiation. Rod photoreceptors stained for the RB1 protein product, pRB, and p107 in only a brief window of postnatal murine development, with no detectable staining for any of the RB family proteins in adult human and mouse rod photoreceptors. Adult mouse and human Muller glia, ganglion and rare horizontal cells, and adult human, but not adult mouse, cone photoreceptors stained for pRB. The RB gene family is dynamically and variably expressed through retinal development in specific retinal cells.

Animals↗

PubMed2005

Cone function studied with flicker electroretinogram during progressive retinal degeneration in RCS rats.

The Royal College of Surgeons (RCS) rat has a primary defect in retinal pigment epithelial cells that leads to the progressive loss of photoreceptors and central visual responsiveness. While most rods are lost by 90 days of age (P90), cones degenerate more slowly, and can be detected anatomically up to 2 years of age, despite massive neuronal death and retinal remodelling. To examine how this progressive degenerative process impacts on cone function, we recorded the electroretingram to white light flashes (1.37 log cd s m(-2)) presented at frequencies ranging from 3 to 50 Hz, under light adapted conditions (29.8 cd m(-2)). Pigmented dystrophic and congenic non-dystrophic RCS rats aged from 18 to 300 days were studied. In all responsive animals at all ages, maximal amplitudes were obtained at 3 Hz. In both non-dystrophic and dystrophic rats, there was an increase from P18 to P21 in response amplitude and critical fusion frequency. After P21, these two parameters declined progressively with age in dystrophic rats. Other changes included prolongation in latency, which was first detected prior to the initiation of amplitude reduction. While phase shifts were also detected in dystrophic RCS rats, they appeared at later degenerative stages. The latest age at which responses could be elicited in dystrophic rats was at P200, with positive waves being replaced by negative deflections. The effect of increments in the intensity of background illumination was tested at P50 in both groups. This caused a diminution in flicker response amplitude and critical fusion frequencies in non-dystrophics, while in dystrophic animals, response amplitudes were reduced only at low frequencies and critical fusion frequencies were unaltered. In conclusion, although dystrophic RCS rats undergo a progressive decline in cone function with age, the flicker responsiveness at P21 is comparable to that of non-dystrophic congenic rats, suggesting normal developmental maturation of the cone system in this animal model of retinal degeneration. Flicker responses can be recorded up to P200, at which point the retina has undergone severe regressive and reactive changes in its connectivity patterns. The fact that responses at this age consist of solely negative deflections might be a reflection of the highly pathological state of the retina.

Aging↗

PubMed2001

Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7/rd7 mice.

The rd7 mouse is a model for hereditary retinal degeneration characterized clinically by retinal spotting throughout the fundus and late onset retinal degeneration, and histologically by retinal dysplasia manifesting as folds and whorls in the photoreceptor layer. This study demonstrates that the rd7 phenotype results from a splicing error created by a genomic deletion of an intron and part of an exon. Hematoxylin/eosin staining of rd7 tissue shows that the whorls in the outer nuclear layer of the retina do not appear during embryonic development but manifest by postnatal day 12.5 (P12.5). Furthermore, in situ hybridization data indicates that the Nr2e3 message is first present at barely discernable levels at embryonic day 18.5, becomes abundant by P2.5, and reaches maximal adult levels by P10.5. Results from these experiments indicate that Nr2e3 message is expressed prior to the development of S-cones. This data coincides with studies in humans showing that mutations in Nr2e3 result in a unique type of retinal degeneration known as enhanced S-cone syndrome, where patients have a 30-fold increase in S-cone sensitivity compared to normal. Immunohistochemical staining of cone cells demonstrates that rd7 retinas have an increased number of cone cells compared to wild-type retinas. Thus, Nr2e3 may function by regulating genes involved in cone cell proliferation, and mutations in this gene lead to retinal dysplasia and degeneration by disrupting normal photoreceptor cell topography as well as cell-cell interactions.

Animals↗

PubMed2002

Cone neurite sprouting: an early onset abnormality of the cone photoreceptors in the retinal degeneration mouse.

PURPOSE: Mutations in many rod genes can cause inherited blinding neurodegeneration in the retina characterized by sequential death of rod and cone photoreceptors. This study was to examine the morphological changes of the cone photoreceptors in retinal degeneration (rd1) mice caused by rod-specific cGMP phosphodiesterase beta-subunit gene mutation and to gain insights into the early cellular events underlying the secondary cone death. METHODS: Transgenic mice that have their living cones labeled by the green fluorescent protein (GFP) transgene and carry the homozygous rd1 mutation were generated, and identified by PCR analysis of the mouse tail DNA and PCR coupled Dde I digestion. The morphology of cone cells in live and fixed retinas from developing and adult mice was examined with fluorescence and scanning laser confocal microscopy. Some fixed mouse retinas were also examined by immunocytochemical staining. Volume images from the confocal three-dimensional (3D) data sets were processed with IMARIS software for 3D view of the detailed cone cell morphology. RESULTS: The cone photoreceptors in the rd1 retinas exhibited a novel process of neurite sprouting, in addition to the general pathological changes of cone degeneration such as shortening and loss of cone outer and inner segments, and loss and death of the cones. The cones gave rise to prominent neurite outgrowth from their axons and synaptic pedicles as well. Most neurites had beaded varicosities along their length and some terminated as bulbous structures. Some cone pedicles showed abnormally elongating and branching processes. The degenerating cones were disorganized, and migrated into the inner nuclear layer. Some cone neurites extended horizontally and appeared to contact the rod bipolar cells, while others projected into the inner plexiform layer. The aberrant cone sprouting started from P8 when rod degeneration generally began, and became evident by P10. In contrast, this abnormal cone neurite sprouting was not observed in the examined control mice that did not carry the rd1 mutation. Double-labeling with cone cell-specific peanut agglutinin confirmed that the fluorescent cells expressing the GFP in the rd1 retinas were indeed the cone photoreceptors. CONCLUSIONS: Cone photoreceptors in the rd1 mice underwent a remarkable process of neurite sprouting that appeared to start before the onset of cone cell death and persisted throughout the course of cone degeneration. This novel process of cone neurite sprouting may be a part of the early cellular events leading to the cone photoreceptor death in retinal degeneration of the rd1 mice.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2001

Photoreceptor plasticity in reaggregates of embryonic chick retina: rods depend on proximal cones and on tissue organization.

Plasticity of photoreceptors and their integration into epithelial structures homologous to an outer nuclear layer (ONL), was investigated in embryonic chick retinal cell reaggregates by immunohistochemistry using an antibody specific for red plus green cones (RG-cones) and an antibody for rods. If reaggregates are raised in the presence of pigmented epithelium (RPE), completely reconstructed, stratified retinal spheres are produced, where all rods and cones are integrated into an outer laminar ONL, similar to a normal retina. In the absence of RPE, 'rosetted' spheres form which contain internal rosettes homologous to an ONL. Only a minor fraction of cones and rods of 'rosetted' spheres are located within rosettes, while a larger fraction is diffusely displaced in nonorganized areas, thus, not contributing to an ONL-like epithelium. In both types of spheres, the total percentage of RG-cones was similar to the in vivo retina, indicating that expression of cones is autonomous. Following cones, after about one day, rods developed only within already existing RG-cone clusters. Thereby, the ratio of rods to RG-cones increases as the tissue organization decreases: for stratified spheres this ratio is, 0.50 (1 rod/2 cones; similar to mature retina); for rosettes, 0.74 (3 rods/4 cones) and for nonorganized areas, 1.09 (1 rod/1 cone) -- a higher ratio under our conditions has never been detected. Thus, rod expression depends strictly on the presence of nearby cones; their relative numbers are distinctively adjusted according to the cytoarchitecture of the tissue environment. The biomedical implications of these findings are briefly discussed.

Animals↗

PubMed2004

Recruitment of the rod pathway by cones in the absence of rods.

In mammalian retinas, rods and cones connect to distinct sets of bipolar cells. In the retina of Nrl (neural retina leucine zipper) knock-out mice, in which rods fail to form and all photoreceptors are cones, rod bipolar cells have normal morphology, pattern of staining, and lamination, but they form synaptic connections with cones. Hence, retinal interneurons are not entirely committed to the choice of their synaptic partners; also, their morphology and pattern of distribution of their processes in the synaptic layers of the retina are not instructed by the establishment of synaptic connections with cognate photoreceptor(s). These findings are of considerable relevance for our understanding of mechanisms responsible for cell recognition during development and in the context of using transplanted tissue to restore vision in retinal degeneration.

Animals↗

PubMed1998

Fine structure of the retinal photoreceptors of the emu (Dromaius novaehollandiae).

The retinal photoreceptors of the emu (Dromaius novaehollandiae) consist of rods, single cones and double (unequal) cones present in a ratio of about 10:1:4 respectively. The rods are long slender cells which are felt to undergo retinomotor movements. The rod outer segment is a stack of bimembranous discs which display shallow peripheral incisures and are all of the same diameter. The rod inner segment displays an ellipsoid of mitochondria, much rough endoplasmic reticulum (ER), numerous polysomes and a prominent hyperboloid of glycogen. Single cones show a tapered outer segment, no oil droplet but a large ellipsoid with several small lipid droplets and a paraboloid of glycogen. Double cones consist of a chief member which displays a single large heterogeneous oil droplet and no paraboloid, and an accessory cone which has no oil droplet but again several small lipid droplets and a large paraboloid. All cones show a large ellipsoid, plentiful polysomes, rough ER, Golgi zones and autophagic vacuoles. Along the length of the contiguous membranes of the two members of the double cones are scattered membrane densifications. The cones are not believed to undergo retinomotor movements in the emu. Rod photoreceptors are relatively small in diameter and hence are closely packed, while the larger cones are not as abundant. Rods and cones (both types) display both invaginated (ribbon) synapses as well as numerous superficial (conventional) synaptic sites.

Animals↗

PubMed1999

Biochemical analysis of a dimerization domain mutation in RetGC-1 associated with dominant cone-rod dystrophy.

Mutations in the photoreceptor membrane guanylyl cyclase RetGC-1 have been linked to autosomal dominant cone-rod dystrophy. Three mutations were identified that alter strictly conserved residues within the RetGC-1 dimerization domain, a region predicted to form an amphipathic alpha-helical coil. Here we report on a biochemical characterization of one of the mutations, a substitution of cysteine for arginine at residue 838. We generated this mutation in vitro and measured its catalytic activity and sensitivity to guanylyl cyclase activating protein 1 (GCAP-1) and GCAP-2. The R838C substitution has several effects. It reduces the overall catalytic ability of RetGC-1 and dramatically reduces stimulation by GCAP-2, although GCAP-2 still appears to interact with the protein. The R838C substitution also increases the apparent affinity of RetGC-1 for GCAP-1 and alters the Ca(2+) sensitivity of the GCAP-1 response, allowing the mutant to be stimulated by GCAP-1 at higher Ca(2+) concentrations than wild type. The diminished response to GCAP-2, which we propose is not likely the cause of cone-rod degeneration in these patients, is interesting mechanistically because it separates the ability to bind a specific GCAP from the ability to be stimulated by it, and it also discriminates between the mechanisms of activation of GCAP-1 vs. GCAP-2. We suggest that the gain-of-function effects of R838C on RetGC-1 stimulated by GCAP-1, which are dominant in vitro and may cause an abnormal increase in cGMP synthesis in dark-adapted photoreceptors, may be the cause of the cone-rod degeneration.

Amino Acid Sequence↗

PubMed2004

Longitudinal diffusion in retinal rod and cone outer segment cytoplasm: the consequence of cell structure.

Excitation signals spread along photoreceptor outer segments away from the site of photon capture because of longitudinal diffusion of cGMP, a cytoplasmic second messenger. The quantitative features of longitudinal diffusion reflect the anatomical structure of the outer segment, known to be profoundly different in rod and cone photoreceptors. To explore how structural differences affect cytoplasmic diffusion and to assess whether longitudinal diffusion may contribute to the difference in signal transduction between photoreceptor types, we investigated, both theoretically and experimentally, the longitudinal diffusion of small, hydrophilic molecules in outer segments. We developed a new theoretical analysis to explicitly compute the longitudinal diffusion constant, Dl, in terms of outer segment structure. Using time-resolved fluorescence imaging we measured Dl of Alexa488 and lucifer yellow in intact, single cones and validated the theoretical analysis. We used numerical simulations of the theoretical model to investigate cGMP diffusion in outer segments of various species. At a given time interval, cGMP spreads further in rod than in cone outer segments of the same dimensions. Across all species, the spatial spread of cGMP at the peak of the dim light photocurrent is 3-5 microm in rod outer segments, regardless of their absolute size. Similarly the cGMP spatial spread is 0.7-1 microm in cone outer segments, independently of their dimensions.

Animals↗

PubMed1998

The major cell populations of the mouse retina.

We report a quantitative analysis of the major populations of cells present in the retina of the C57 mouse. Rod and cone photoreceptors were counted using differential interference contrast microscopy in retinal whole mounts. Horizontal, bipolar, amacrine, and Müller cells were identified in serial section electron micrographs assembled into serial montages. Ganglion cells and displaced amacrine cells were counted by subtracting the number of axons in the optic nerve, learned from electron microscopy, from the total neurons of the ganglion cell layer. The results provide a base of reference for future work on genetically altered animals and put into perspective certain recent studies. Comparable data are now available for the retinas of the rabbit and the monkey. With the exception of the monkey fovea, the inner nuclear layers of the three species contain populations of cells that are, overall, quite similar. This contradicts the previous belief that the retinas of lower mammals are "amacrine-dominated", and therefore more complex, than those of higher mammals.

Animals↗

PubMed1997

Spatiotemporal coordination of rod and cone photoreceptor differentiation in goldfish retina.

In this study, we have compared spatial and temporal aspects of development of new rods and cones in the adult goldfish by using a combination of bromodeoxyuridine immunocytochemistry and opsin in situ hybridization to determine the intervals between terminal mitosis (cell "birth") and expression of opsin mRNA for each photoreceptor cell type. The goldfish opsins include rod opsin and four different cone opsins: red, green, blue, and ultraviolet. In a cohort of photoreceptors born at the same time, rods expressed opsin mRNA within 3 days of cell birth, while expression of cone opsin mRNA required at least 7 days. This temporal discrepancy in differentiation, coupled with a discordance in the site of cell genesis of rods and cones, allowed opsin expression to commence in both cell types in approximately the same retinal location. Commitment to the generic cone phenotype occurred within approximately 6 days throughout the cone cohort, as indicated by expression of interphotoreceptor retinoid-binding protein (IRBP) mRNA, but expression of a specific spectral phenotype was delayed until rods differentiated nearby. Onset of expression of cone opsin mRNA followed a phenotype-specific sequence: red, then green, then blue, and finally ultraviolet; in situ hybridization with two opsin probes confirmed that individual photoreceptors expressed only one type of opsin as they differentiated. This stepwise process of cone differentiation is consistent with the hypothesis that cell-cell interactions among developing photoreceptors may coordinate selection of specific photoreceptor phenotypes.

Animals↗

PubMed2006

Antioxidants reduce cone cell death in a model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a label for a group of diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cones. The mechanism of cone cell death is uncertain. Rods are a major source of oxygen utilization in the retina and, after rods die, the level of oxygen in the outer retina is increased. In this study, we used the rd1 mouse model of RP to test the hypothesis that cones die from oxidative damage. A mixture of antioxidants was selected to try to maximize protection against oxidative damage achievable by exogenous supplements; alpha-tocopherol (200 mg/kg), ascorbic acid (250 mg/kg), Mn(III)tetrakis (4-benzoic acid) porphyrin (10 mg/kg), and alpha-lipoic acid (100 mg/kg). Mice were treated with daily injections of the mixture or each component alone between postnatal day (P)18 and P35. Between P18 and P35, there was an increase in two biomarkers of oxidative damage, carbonyl adducts measured by ELISA and immunohistochemical staining for acrolein, in the retinas of rd1 mice. The staining for acrolein in remaining cones at P35 was eliminated in antioxidant-treated rd1 mice, confirming that the treatment markedly reduced oxidative damage in cones; this was accompanied by a 2-fold increase in cone cell density and a 50% increase in medium-wavelength cone opsin mRNA. Antioxidants also caused some preservation of cone function based upon photopic electroretinograms. These data support the hypothesis that gradual cone cell death after rod cell death in RP is due to oxidative damage, and that antioxidant therapy may provide benefit.

Animals↗

PubMed2001

The ability of hyperoxia to limit the effects of experimental detachment in cone-dominated retina.

PURPOSE: To determine the ability of oxygen supplementation to ameliorate the effects of retinal detachment in a cone-dominated retina. METHODS: Retinal detachments were created in the right eyes of ground squirrels and the animals immediately placed in normoxic (room air) or hyperoxic (70% oxygen) conditions for 3 days. The retinas were sampled from different regions and investigated morphologically or immunocytochemically by light or confocal microscopy. Agarose embedded sections were immunostained with antibody probes to cytochrome oxidase, synaptophysin, medium-to-long wavelength-sensitive (M/L) cone opsin, rod opsin, excitatory amino acid transporter 1 (EAAT1), glutamate synthetase (GS), cellular retinaldehyde-binding protein (CRALBP), and peanut agglutinin (PNA) lectin. Retinal wholemounts were labeled with PNA and antibodies to short (S)-wavelength-sensitive cone opsin and rod opsin. Cell death was examined using a TUNEL assay on agarose sections or using toluidine blue staining on semithin sections. RESULTS: The percentage of dying cells relative to the total nuclei in the photoreceptor layer was significantly reduced, and the total number of nuclei was greater in hyperoxic animals. Triple labeling using TUNEL, anti-M/L cone opsin and anti-rod opsin showed that hyperoxia had a remarkable effect both on the reduction of cone cell death and the maintenance of the overall structure of cone photoreceptors. Analysis of the retinal wholemounts demonstrated the preservation of PNA, S-cone, and rod opsin antibody labeling in the detachments maintained in hyperoxic conditions. Although the disruption of cytochrome oxidase and synaptophysin was seen in normoxic animals, there was minimal disruption in hyperoxic animals. Labeling with anti-EAAT1, anti-GS, and anti-CRALBP was increased in the Müller cells of normoxic animals with detachments, but was decreased in the hyperoxic animals. CONCLUSIONS: Hyperoxia prevents the degeneration of both rods and cones in retinas heavily dominated by cones and mitigates the effect of detachment on Müller cell reactivity. The current results suggest that the rescue of cones is not secondary to that of rods.

Animals↗

PubMed2000

Cone differentiation with no photopigment coexpression.

PURPOSE: To decide whether the transitory coexpression of cone visual pigments described in the developing rat and gerbil retina is a universal feature of dichromatic mammalian species. METHODS: The rabbit, a species widely used in eye research, was selected for the study and a search made for the presence of cones that bound more than one cone antibody during the first postnatal week. To plot the densities of individual cone types and to colocalize the two visual pigments, immunocytochemistry on retinal wholemounts and consecutive tangential sections, respectively, were used. RESULTS: The sequence in which the visual pigments began to be expressed was the same as that observed in other mammals: first, rhodopsin; second, blue pigment; and last, green pigment. The striking increase in blue cone density numbers observed in the rat, however, did not occur in the rabbit. Instead, some days after the first blue cones appeared, the green cones also started to express their visual pigment, and this cone type soon outnumbered the blue cones. Within the limits of the immunocytochemical method, it was established that unlike the developing rat, the presence of double-labeled cones was not a character of the rabbit retina. CONCLUSIONS: Visual pigment coexpression is an interesting phenomenon of retinal development, however, it is not the exclusive scenario of photoreceptor differentiation. Each species must be carefully studied before deciding whether its retinal cones synthesize both pigments during retinal development.

Animals↗

PubMed1999

[A study on transplantation of rat photoreceptor cell layer].

OBJECTIVE: To study the relationship between photoreceptors and other layers of the retina in the aspects of anatomical structure, physiology, pathology, etc. METHODS: RCS rats were used as host animals, and the pure cone and rod layer of the donor retina was prepared from Wistar rat and was transplanted under the host retina where the cones and rods were degenerated. RESULTS: After 2 weeks of transplantation, the retinas of the host rats were reattached, and the transplanted cells were survival. The transplanted cells were in the subretinal space between the retinal pigment epithelium (RPE) and the inner unclear layer, and they had the staining characteristics similar to that of the normal control photoreceptors. CONCLUSION: In the animal model of photoreceptor cell layer transplantation, the transplanted cells possess normal anatomical location and are connected with RPE and inner nuclear layer. The results provide a new route to investigate the re-establishment of anatomical association with the optic nerve and the physiological activity of the nerve.

Animals↗

PubMed1999

Immunocytochemical localization of taurine in the developing retina of the lefteye flounder Paralichthys olivaceus.

Light microscopic immunolocalization of taurine, a sulfur-containing free amino acid, was investigated in the developing retina of a lefteye flounder, Paralichthys olivaceus, which exhibits metamorphic changes with rod cell addition for 3-5 weeks after hatching. This immunocytochemical study of the developing retina revealed: 1) From 3 to 13 days after hatching, intense immunostaining was shifted from the surroundings of neural cells to the neural somata and processes in the inner retina. 2) Intense immunoreactivity appeared also in the outer and inner segments and basal processes (pedicles) of cone cells within 6 days or 13 days after hatching. 3) Lack of immunoreactivity was found in the outer segment of rod cells from their appearance during metamorphosis. These findings are discussed with the possible functional roles of taurine in the fish retina: 1) involvement in cell differentiation and/or development; 2) protection of the outer segments against light stimuli; and 3) regulation of neural transmission.

Age Factors↗

PubMed1997

Photoreceptor transplants increase host cone survival in the retinal degeneration (rd) mouse.

Retinal transplants offer a potentially interesting approach to treating human retinal degenerations, but so far little quantitative data are available on possible beneficial effects. We isolated photoreceptor layers from normal-sighted mice and grafted them into the subretinal space of retinal degeneration (rd) mice lacking rod photoreceptors. At 2 weeks after surgery, the numbers of residual host cone photoreceptors outside the graft zone were quantified following specific labelling. Examination of operated retinas revealed highly significantly greater numbers of surviving cones (mean of 38% more at 2 weeks) within the central field compared to sham-operated paired control retinas (p < 0.01). These are the first quantified data indicating a trophic effect of transplanted photoreceptors upon host cone cells. As cone cells are responsible for high acuity and colour vision, such data could have important implications not only for eventual therapeutic approaches to human retinal degenerations but also to understanding underlying interactions between retinal photoreceptors.

Animals↗

PubMed1997

Age-related distribution of cones and ON-bipolar cells in the rd mouse retina.

PURPOSE: Retinal dystrophic (rd) mice lose most of their rod photoreceptors within the first three weeks after birth. We determined the age-related distribution of peanut agglutinin lectin (PNA)-labeled cones during the first 12 months of age. We also investigated whether the density of ON-bipolar cells expressing L7 protein was affected by their loss of photoreceptor inputs. METHODS: rd mice were selected from a transgenic strain which expresses an L7-beta-galactosidase fusion gene localized to ON-bipolar cells. Cones were stained with PNA and ON-bipolar cells with bluo-gal (halogenated indolyl-beta-D-galactoside). Retinas were flat-mounted and observed at 1, 2, 3, 6 and 12 months of age. RESULTS: PNA-labeled cones are distributed unevenly across the retina at 1 month postnatal. Their concentration decreases first in the central and far peripheral retina, leaving a ring of labeled cells in the midperipheral region. At 3 months, a larger patch of cones remains in the supero-temporal midperipheral region and a smaller patch in the infero-nasal retina. By 6 months, few cones remain in the infero-nasal retina; by 1 year approximately 100 cones remain in the entire retina, localized to the superior midperipheral region. ON-bipolar cells appear evenly distributed at 1 month. By 2-3 months, relatively more bluo-gal staining is seen in the midperipheral regions underlying dense cone populations. At 6-12 months, bluo-gal label is distributed in a spotty pattern with little or no staining seen in areas of apparent neovascularization. CONCLUSIONS: (1) PNA-labeling of cones in the rd retina deteriorates in a distinct spatial pattern with the longest cone survival in the midperipheral superior retina. (2) ON-bipolar cells are more densely labeled in regions of high cone density during the early months of cone degeneration and, in later stages, show relative decreases in regions of apparent neovascularization.

Age Factors↗