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At least 19 recordsLinked to original sources
PubMed2001

Oxygen distribution and consumption within the retina in vascularised and avascular retinas and in animal models of retinal disease.

Maintenance of an adequate oxygen supply to the retina is critical for retinal function. In species with vascularised retinas, such as man, oxygen is delivered to the retina via a combination of the choroidal vascular bed, which lies immediately behind the retina, and the retinal vasculature, which lies within the inner retina. The high-oxygen demands of the retina, and the relatively sparse nature of the retinal vasculature, are thought to contribute to the particular vulnerability of the retina to vascular disease. A large proportion of retinal blindness is associated with diseases having a vascular component, and disrupted oxygen supply to the retina is likely to be a critical factor. Much attention has therefore been directed at determining the intraretinal oxygen environment in healthy and diseased eyes. Measurements of oxygen levels within the retina have largely been restricted to animal studies in which oxygen sensitive microelectrodes can be used to obtain high-resolution measurements of oxygen tension as a function of retinal depth. Such measurements can immediately identify which retinal layers are supplied with oxygen from the different vascular elements. Additionally, in the outer retinal layers, which do not have any intrinsic oxygen sources, the oxygen distribution can be analysed mathematically to quantify the oxygen consumption rate of specific retinal layers. This has revealed a remarkable heterogeneity of oxygen requirements of different components of the outer retina, with the inner segments of the photoreceptors being the dominant oxygen consumers. Since the presence of the retinal vasculature precludes such a simple quantitative analysis of local oxygen consumption within the inner retina, our understanding of the oxygen needs of the inner retinal components is much less complete. Although several lines of evidence suggest that in the more commonly studied species such as cat, pig, and rat, the oxygen demands of the inner retina as a whole is broadly comparable to that of the outer retina, exactly which cell layers within the inner retina have the most stringent oxygen demands is not known. This may be a critical issue if the cell types most at risk from disrupted oxygen supply are to be identified. This paper reviews our current understanding of the oxygen requirements of the inner and outer retina and presents new data and mathematical models which identify three dominant oxygen-consuming layers in the rat retina. These are the inner segments of the photoreceptors, the outer plexiform layer, and the deeper region of the inner plexiform layer. We also address the intriguing question of how the oxygen requirements of the inner retina are met in those species which naturally have a poorly vascularised, or even totally avascular retina. We present measurements of the intraretinal oxygen distribution in two species of laboratory animal possessing such retinas, the rabbit and the guinea pig. The rabbit has a predominantly avascular retina, with only a narrow band of retinal vasculature, and the guinea pig retina is completely avascular. Both these animals demonstrate species adaptations in which the oxygen requirement of their inner retinas are extremely low when compared to that of their outer retinas. This finding both uncovers a remarkable ability of the inner retina in avascular species to function in a low-oxygen environment, and also highlights the dangers of extrapolating findings from avascular retinas to infer metabolic requirements of vascularised retinas. Different species also demonstrate a marked diversity in the manner in which intraretinal oxygen distribution is influenced by increases in systemic oxygen level. In the vascularised rat retina, the inner retinal oxygen increase is muted by a combination of increased oxygen consumption and a reduction of net oxygen delivery from the retinal circulation. The avascular retina of the guinea pig demonstrated a novel and powerful regulatory mechanism that prevents any dramatic rise in choroidal oxygen levels and keeps retinal oxygen levels within the normal physiological range. In contrast, in the avascular regions of the rabbit retina the choroidal oxygen level passively follows the increase in systemic oxygenation, and there is a dramatic rise in oxygen level in all retinal layers. The presence or absence of oxygen-regulating mechanisms may well reflect important survival strategies for the retina which are not yet understood. Intraretinal oxygen measurements in rat models of retinal disease are also presented. We describe how oxygen distribution across the rat retina is influenced by manipulation of systemic blood pressure. We examine the effect of acute and chronic occlusion of the retinal vasculature, and explore the feasibility of meeting the oxygen needs of the ischemic retina from the choroid. (ABSTRACT TRUNCATED)

Animals↗
PubMed1982

Adenylate cyclases in vertebrate retina: enzymatic characteristics in normal and dystrophic mouse retina.

Adenylate cyclase activity and the effects of various activators and inhibitors of this enzyme were measured in retinas from normal mice (C57BL/6J) and congenic animals with photoreceptor dystrophy. In normal retina, approximately 250 microM-ATP was required for half-maximal stimulation of the enzyme. Activity was supported by Mg2+ and Mn2+, but Ca2+ was ineffective. The enzyme was inhibited by EGTA and stimulated by 5'-guanylylimidodiphosphate (GPP(NH)P), dopamine, and NaF. The stimulatory effects of GPP(NH)P and dopamine were greater in the presence of EGTA. Examination of microdissected normal retinas revealed that the inner (neural) retina had adenylate cyclase activity four times that of the photoreceptor cell layers, and that EGTA inhibited activity in the inner retina, but had no effect in the outer retina. In dystrophic retinas basal enzyme activity was 60% higher than that in normal retina. The enzyme in this tissue was stimulated by EGTA, GPP(NH)P, and dopamine, and their effects were additive. These results indicate that adenylate cyclase activity in vertebrate retina is under complex regulation by substrate, divalent cations, guanine nucleotides, dopamine, and perhaps calmodulin. In addition, the data demonstrate that adenylate cyclase is not evenly distributed in the retina and that it is regulated differently in the inner and outer retina. Finally, the present results indicate that regulation of this enzyme in dystrophic retina may be qualitatively and quantitatively different from that in normal retina.

Adenylyl Cyclases↗
PubMed2003

Identification of novel genes preferentially expressed in the retina using a custom human retina cDNA microarray.

PURPOSE: To construct a custom cDNA microarray for comprehensive human retinal gene expression profiling and apply it to the identification of genes that are preferentially expressed in the retina. METHODS: A cDNA microarray was constructed based on the predicted human retina gene expression profile according to expressed sequence tag (EST) databases. Gene expression profiles were obtained from five human retinas, two livers, and the cerebral cortical regions of two brains. Each sample was studied in duplicate, using a reference sample experimental design. Retina-enriched genes were identified by using the significance analysis for microarray (SAM) algorithm. Quantitative real time PCR was used to confirm microarray results. Bioinformatic analysis was performed to compare the array results with expression data available from public databases. RESULTS: The cDNA microarray contains 10,034 sequences: 67% represent known genes and 33% represent ESTs. Differential hybridization with the array identified, in addition to known retinal genes, 186 retina-enriched genes that do not have known retinal function. Of these, 96 represent novel genes. Quantitative real-time PCR of 11 of the identified genes and ESTs confirmed their retina-enriched expression pattern. Bioinformatic analysis of EST databases suggests that of the 186 genes, approximately 40% are predominantly expressed in the retina, whereas the remainder show significant expression in other tissues. Comparison of this study's microarray-based retina-enriched gene set with three published similar sets identified using complementary high-throughput approaches demonstrated only limited overlap of the identified genes. CONCLUSIONS: Because previous studies have demonstrated that many retina-enriched genes are crucial for maintaining normal retinal function, the genes identified here are likely to include ones that have important roles in the retina and ones that when mutated can cause or modulate retinal disease. In addition, the retina custom array should provide a useful resource for comparing expression profiles between normal and diseased human retinas.

Adult↗
PubMed2002

Expressed sequence tag analysis of human retina for the NEIBank Project: retbindin, an abundant, novel retinal cDNA and alternative splicing of other retina-preferred gene transcripts.

PURPOSE: Expressed sequence tag (EST) analysis was performed on un-normalized, unamplified cDNA libraries constructed from adult human retina to examine the expression profile of the tissue and to contribute resources for functional genomics studies. METHODS: Two size fractionated cDNA libraries (designated hd and he) were constructed from human retina RNA. Clones were randomly selected for sequencing and analyzed using the bioinformatics program GRIST (GRouping and Identification of Sequence Tags). PCR, Northern blotting and other techniques have been used to examine selected novel transcripts. RESULTS: After informatics analysis, 2200 retina cDNAs yield 1254 unique clusters, potentially representing individual genes. Opsin is the most abundant transcript and other retina transcripts are prominently represented. One abundant cluster of cDNAs encodes retbindin, a novel, retina preferred transcript which has sequence similarity to riboflavin binding proteins and whose gene is on chromosome 19. Variant transcripts of known retina genes are also observed, including an alternative exon in the coding sequence of the transcription factor NRL and a skipped coding sequence exon in the phosphodiesterase gammasubunit (PDE6G). CONCLUSIONS: The new retina cDNA libraries compare favorably in quality with those already represented in public databases. They are rich in retina specific sequences and include abundant cDNAs for a novel protein, retbindin. The function of retbindin remains to be determined, but it is a candidate for flavinoid or carotenoid binding. Analysis of multiple clones for highly expressed retina genes reveals several alternative splice variants in both coding and noncoding sequences which may have functional significance. The validated set of retina cDNAs will contribute to a nonredundant set for microarray construction.

Aged↗
PubMed1986

Axolotl retina and lens development: mutual tissue stimulation and autonomous failure in the eyeless mutant retina.

During eye development in the axolotl (Ambystoma mexicanum Shaw), morphogenetic movements bring together tissues from head epidermis, neuroectoderm and neural crest. The stages 0 to 14 of axolotl eye development were expanded from Rabl's (1898) stages 1 to 10 and correlated with Harrison's (1969) stages. At the onset of neurulation (stage 13 of Harrison), the head epidermis is already determined to form skin, and the neuroectoderm is committed to form brain, because these tissues develop autonomously in 60% Leibovitz L-15 culture medium. However, a sequence of mutual tissue interactions is necessary to stimulate eye development. When head epidermis and neuroectoderm were cocultured, eyes developed, containing retinas with photoreceptors (stage 8) and lenses with secondary lens fibres (stage 8). The first event needed in this case appears to be the secretion of a growth factor from the head epidermis which stimulates retina development from the neuroectoderm. When neuroectoderm cultures were exposed to nondialysable extracts (30 micrograms ml-1) of an adult epidermis derivative, the bovine cornea, pigmented retinas (stage 6) and at higher concentrations (3000 micrograms ml-1) neural retinas developed (stage 6). In turn, lens formation is stimulated in the head epidermis by a retina-derived growth factor. A mutation that causes adult eyelessness (e eyeless, nonlethal, recessive) affects the earliest event in eye development (stage 1a), while a mutation that causes arrest of eye development (mi microphthalmic, lethal, recessive) acts in a later event (stage 8). Two possibilities have been considered in the case of mutation e: either the head epidermis does not secrete sufficient amounts of active growth factor, or the presumptive retina itself is defective. The latter statement turned out to be correct, because mutant e neural plates rarely developed early retina stages (stage 5) in organ culture when combined with wild-type head epidermis. On the other hand, wild-type neural plates formed advanced retinas (stage 8) in all cases when combined with mutant e head epidermis. As expected, no retina or lens developed when both neural plate and head epidermis were from mutant e donors. The heterozygous presence of genes e and r (renal insufficiency, lethal, recessive) produces duplications of the presumptive retina at the optic stalk. This observation is consistent with the notion that the mutation e, assisted by the r locus, causes a primary failure in the presumptive retinal region.

Ambystoma↗
PubMed2000

Diabetes reduces glutamate oxidation and glutamine synthesis in the retina. The Penn State Retina Research Group.

Retinas of diabetic individuals develop early functional changes measurable by electrophysiological and psychometric testing. Using a rat model of diabetes, we previously identified diabetes-induced alterations in metabolism of the neurotransmitter glutamate which may ultimately lead to accumulation of glutamate in the retina (Diabetes, 47: 815, 1998). We therefore investigated the function of enzymes that mediate the synthesis and breakdown of glutamate in retinas from rats made diabetic by injection of streptozotocin. De novo synthesis of nitrogen-containing amino acids including glutamate, glutamine and aspartate was assessed by measuring the rate of carbon fixation in freshly dissected retinas, and was unchanged by diabetes. In contrast, the oxidation of glutamate was significantly reduced in retinas from diabetic rats (62%, P < 0.05). Furthermore, diabetic retinas were less susceptible to inhibition of glutamate oxidation by the transaminase inhibitor aminoxyacetate (80%, N.S.), compared to the significant decrease seen in control rats (61%, P < 0.001). The activity and content of glutamine synthetase were also significantly reduced in retinas from rats diabetic for 2-6 months [range of 48% (P < 0.005) to 83% (P < 0.05) compared to control]. The activity of glutamine synthetase was normalized by acute injections of insulin, but not by reducing blood sugar levels with injections of phlorizin. These results indicate two enzymatic abnormalities in the glutamate metabolism pathway in the retina during diabetes: transamination to alpha-ketoglutarate and amination to glutamine. The reduced flux through these pathways may be associated with the accumulation of glutamate. These results are also consistent with the possibility that some of the glial changes in the retina during diabetes may be caused by hypoinsulinemia rather than hyperglycemia.

Animals↗
PubMed1980

Ontogeny of the retina and optic nerve in Xenopus laevis. II. Ontogeny of the optic fiber pattern in the retina.

The ontogeny of optic fiber patterns within the Xenopus laevis retina has been studied in silver-stained serial sections and whole mounts. Ganglion cell axons ("pioneers") appear much earlier than previously recognized, at Nieuwkoop-Faber ('56) Stage 28. Fibers fasciculate into bundles as they arise in the retina and reach the chiasma by NF Stage 32. Because the retina grows in rings at its margins, ganglion cell axons differentiate at the periphery and join the nearest fiber bundles (fascicles) to reach the optical disc. A radial fascicle pattern develops by Stage X (Grant et al., '80) within the optic fiber layer of the retina and acts as a template of pathways that lead all later appearing fibers out of the retina. Since the retina grows asymmetrically along its dorso-ventral axis, the fascicle pattern develops asymmetrically, with dorsal quadrant fascicles forming an arcuate pattern in contrast to shorter, thicker ventral quadrant fascicles. The growth pattern of the retina and the "principle" of fiber following suggest that "positional information" is acquired by ganglion cells according to a system of polar coordinates (MacDonald, '77). A radial distance "r" from the center is determined temporarily by ganglion cell birthday and an angular value "theta" is given by the angular position of the fascicle followed by its axons to the optical disc. Wedges of ganglion cells send their axons into a common fascicle which retains its integrity as it leaves the retina at the optic disc. This pattern of optic fiber development suggests a model for retino-topic ordering of the optic fiber projection in Xenopus, with the fascicle acting as the "pattern-forming unit of connectivity."

Animals↗
PubMed1986

GABA neurones in retinas of different species and their postnatal development in situ and in culture in the rabbit retina.

The localisation of GABA immunoreactive neurones in retinas of a variety of animals was examined. Immunoreactivity was associated with specific populations of amacrine neurones in all species examined, viz. rat, rabbit, goldfish, frog, pigeon and guinea-pig. All species, with the exception of the frog, possessed immunoreactive perikarya in their retinal ganglion cell layers. These perikarya are probably displaced amacrine cells because GABA immunoreactivity was absent from the optic nerves and destruction of the rat optic nerve did not result in degeneration of these cells. GABA immunoreactivity was also associated with the outer plexiform layers of all the retinas studied; these processes are derived from GABA-positive horizontal cells in rat, rabbit, frog, pigeon and goldfish retinas, from bipolar-like cells in the frog, and probably from interplexiform cells in the guinea-pig retina. The development of GABA-positive neurones in the rabbit retina was also analysed. Immunoreactivity was clearly associated with subpopulations of amacrine and horizontal cells on the second postnatal day. The immunoreactivity at this stage is strong, and fairly well developed processes are apparent. The intensity of the immunoreactivity increases with development in the case of the amacrine cells. The immunoreactive neurones appear fully developed at about the 8th postnatal day, although the immunoreactivity in the inner plexiform layer becomes more dispersed as development proceeds. The immunoreactive horizontal cells become less apparent as development proceeds, but they can still be seen in the adult retina. The GABA immunoreactive cells in rabbit retinas can be maintained in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The retinae of Prototherian mammals possess neuronal types that are characteristic of non-mammalian retinae.

This study has shown that the retinae of Prototherian (egg-laying) mammals possess two neuronal types that are present in non-mammalian retinae, but absent or morphologically different in the retinae of Eutherian (placental) mammals. First, endogenous serotonin-like immunoreactivity has been localized in a population of presumptive amacrine cells in the platypus retina, the first such report in a mammalian retina. Second, the protein kinase C-immunoreactive (PKC-IR) bipolar cells in the echidna retina appear similar to the PKC-IR bipolars in the chicken retina, in that their dendrites give rise to a Landolt's club and their axons are multistratified. By contrast, the PKC-IR rod bipolar cells in the rabbit and in the brushtail possum, a Metatherian (marsupial) mammal, have no Landolt's clubs and their axons form terminal lobes in the innermost stratum of the inner plexiform layer.

Animals↗
PubMed1976

Isolation of retina-specific cell-aggregating factor from membranes of embryonic neural retina tissue.

There is increasing evidence that developmental associations among embryonic cells are mediated by specific components of the cell surface. Earlier work has indicated that such components are extruded into the medium of primary monolayer cultures of embryonic cells, and that they represent the active constituents of the tissue-spedific cell-aggregating factors isolated fro- the supernatant medium of such cultures. We presently report that tissue-specific cell-aggregating factors can be obtained directly from embryonic tissues, and describe the isolation and partial purification of retina-spedific factor from a cell-membrane preparation derived from retina tissue of the chick embryo. Extraction of the purified membrane preparation with 1-butanol yielded an activity in the aqueous phase which resides in a protein probably a glycoprotein, with an estimated molecular weight of 50,000 in solution. This material could be obtained from retinas of embryos not older than 13 days, and only pre-13-day cells responded to its cell-aggregating activity. By these characteristics, this membrane-derived retina factor closely resembles the retina cell-aggregating glycoprotein previously purified from the supernatant medium of retina cell cultures. It is of special interest that the cell-aggregating protein is obtainable from cellular membranes during those stages of development when retina cells are most actively engaged in histological organization. Work in progress indicates that, by the procedures described herein, tissue-specific cell-aggregating factors can also be obtained from membrane preparations of other embryonic tissues.

Age Factors↗
PubMed1989

[Studies on the ultrastructure of the inner limiting membrane of the retina. I. Surface replication study on the inner limiting membrane of the retina].

In order to clarify the ultrastructural details, electron microscopic observations of the inner limiting membrane (ILM), critical point drying and surface replication methods with collagenase digestion were performed on rabbit's ILM. The results were as follows,: 1) This method was simple, the electron microscopic image is highly reproducible and a bird's-eye view of the ILM is possible. 2) The ILM was composed of a fine three-dimensional meshwork structure with numerous pores (sieves). 3) The diameter of the pores varied from 10 to 25nm. Mean diameter of the pores is 13.43nm in the visual streak, 13.59nm in the medullary ray, 13.40nm in the peripheral retina, and there were no statistical differences among these three regions. 4) In the peripheral retina, it was difficult to observe the ILM because vitreous fibrils lay densely on it. The pore's shape in the peripheral retina was different from that in the posterior pole retina. These results may provide the morphological basis for the theory that the pores of the ILM act as the main filtration barrier between the retina and the vitreous cavity. It is supposed that the bulk of substances are transported from the retina mainly through the ILM of the posterior pole, because dense vitreous fibrils of the peripheral retina disturb that transport.

Animals↗
PubMed1989

Distribution and spatial geometry of dopamine interplexiform cells in the rat retina: I. Developing retina.

The morphology and distribution of dopaminergic interplexiform cells were analyzed in 9-day-old rat retinas processed as wholemounts for tyrosine hydroxylase immunohistochemistry. The mean number of dopaminergic interplexiform cells was estimated as about half of the total number of dopaminergic neurons in the immature retina, with a higher density in the temporal retina. Four interplexiform cells were individually analyzed and reconstructed with a computer system. Their arborizations could be divided into three different regions based on both their morphological features and their position within the retinal layers: (1) an internal arborization, spreading at the margin between the inner nuclear layer and the inner plexiform layer, composed of long, thick, somatofugal dendrites branching at acute angles, (2) an external arborization in the middle of the inner nuclear layer, formed by short, thin, varicose, recurved, axon-like processes branching at right angles, (3) and one or more scleral process(es), originating either from the cell body or from the internal arborization, running toward the outermost cell row of the INL, some of which reached the outer plexiform layer. Finally, analysis of the arborization network by computer simulations based on the 4 digitalized cells was compared with a nearest-neighbour analysis of cell body distribution. It showed that cell bodies are almost randomly distributed--at least in the inferior retina--but that an adjustment of dendritic growth and orientation probably occurs to ensure a homogeneous coverage of the retina with a constant degree of overlap in the adult. This report represents the first three-dimensional computer reconstruction of chemically identified neurons in the retina.

Animals↗
PubMed1998

Changes in epidermal growth factor receptor expression and competence to generate glia regulate timing and choice of differentiation in the retina.

Previous studies demonstrated that the level of epidermal growth factor receptors (EGF-Rs) expressed by progenitor cells in the newborn (P0) rat retina was limiting for the generation of Muller glial cells but not for proliferation. To determine whether EGF-R signaling biases cells to generate a specific cell type or regulates more general processes during progenitor cell development, we have introduced extra copies of the EGF-R into progenitor cells at earlier stages (E15 and E18), when different cell types are produced. We show that progenitor cells in early embryonic retina (E15) normally express lower levels of EGF-Rs than progenitor cells in later retina (E18 and P0). Whereas lower levels of stimulation of endogenous and virally transduced EGF-Rs enhanced proliferation, higher levels reduced proliferation, resulting in premature differentiation. At E15, very few EGF-R-Infected progenitor cells differentiated prematurely into Muller glial cells, unlike E18 and P0 cells, even when they were exposed to an older retinal environment. Higher levels of EGF-R-mediated signaling alone therefore do not specify a glial fate, indicating that competence to generate glia is temporally regulated by additional mechanisms. The differences in EGF-R expression observed among retinal progenitor cells at distinct developmental stages may instead help to define signaling thresholds which delay or accelerate their differentiation.

3T3 Cells↗
PubMed1983

Localization of retina cognin in embryonic neural retina tissue by immuno-scanning electron microscopy.

The retina cognin (a retina-specific cell-surface glycosylated protein that mediates self-recognition and morphogenetic contact associations of embryonic retina cells) was visualized by immunolabeling and scanning electron microscopy on the surface of cells within retina tissue of 9- and 16-day chick embryos. The photoreceptor processes which are free of contact with cells in the neural retina, were found to be devoid of surface cognin from early on in their development. These results extend previous studies on cognin localization and regeneration on separated retina cells in vitro and conclusively correlate its presence and surface topology with its postulated role.

Animals↗
PubMed1991

Cryopreservation and transplantation of immature rat retina into adult rat retina.

A bank of freeze-stored donor retinas would free transplantation research from dependence on availability of fresh donor tissue. Donor retinas from E13, E16, E19 and E22 (P1) rat embryos were cryoprotected and stored in liquid nitrogen for up to 8 months. Cryopreserved and fresh donor retinas were grafted to adult rat retina. After 4 weeks survival, transplants were evaluated according to a scoring protocol for the criteria of size, viability, lamination and integration. All donor ages of fresh and cryopreserved retina resulted in successful transplants, with the exception of cryopreserved E13. Cryopreserved grafts were significantly less laminated than grafts of fresh tissue. The best lamination scores of cryopreserved transplants were achieved with donor age E16. Surviving transplants were found in the epiretinal and/or subretinal space. Subretinal transplants had higher viability scores than did epiretinal grafts; the difference was more pronounced with transplants of cryopreserved than with fresh tissue. Fresh subretinal transplants were also significantly better laminated than fresh epiretinal transplants. This study shows that (1) cryopreserved retinal donor tissue can successfully be transplanted to rat retina; and (2) the subretinal space appears to be more favorable than the epiretinal space for retinal transplants.

Animals↗
PubMed1994

Photoreceptor and glial markers in human embryonic retina and in human embryonic retinal transplants to rat retina.

The purpose of this study was to compare the development of photoreceptor and glial cells in human embryonic retinal transplants with the development of normal human embryonic retina (13-20 weeks postconception). Human embryonic retinal cells (donor age 6-11 weeks postconception) were transplanted to the retinas of adult immunosuppressed rat hosts. Host animals were killed when the transplants were of 13-37 weeks total age (donor age+survival time after surgery). Immunohistochemistry was performed with antibodies specific for neuron-specific enolase (NSE), synaptophysin (SYN), cone-specific opsins, rhodopsin, rod alpha-transducin, S-antigen, vimentin, cellular retinaldehyde-binding protein (CRALBP) and glial fibrillary acidic protein (GFAP). With regards to photoreceptors, NSE and SYN immunoreactive cones were seen in transplants from 14-16 weeks of age, but cone opsin immunoreactivity was not seen until 25 weeks. Developing graft rods became S-antigen immunoreactive at 17-18 weeks. At 20 weeks, inner segments and some cell somas of graft rods stained faintly for alpha-transducin and rhodopsin. At 31 and 37 weeks, inner and outer rod segments were intensely labelled for the rod-specific antigens. The grafts exhibited areas of varying maturation with different staining intensities. Concerning the glial cells, vimentin immunoreactivity was seen in the earliest transplants studied (total age 14-16 weeks), but only in stages older than 19 weeks was the immunoreactivity of graft Müller cells comparable in intensity to those of the host retina. Host Müller cells were immunoreactive for GFAP near the lesion site at all times. At 20 weeks, some GFAP immunoreactive processes were seen inside the graft, apparently coming from the host retina. At 25 weeks, faintly stained Müller cells intrinsic to the graft were observed, indicating a gliosis within the graft. Graft Müller cells were first seen to express CRALBP immunoreactivity at 19-20 weeks and, at 25 weeks, intense immunoreactivity was seen in the transplant, mostly in regions near the host. In the transplants only the Müller cells were stained, whereas both Müller and retinal pigment epithelium cells were CRALBP immunoreactive in the host retina. The development of human embryonic retinal transplants appears to parallel approximately normal in utero development. Transplant cones, rods and Müller cells all express their cell-specific proteins. The photoreceptors develop both inner and outer segments and contain several essential proteins for processing light. The transplants can reach a degree of maturity comparable to newborn retina.

Animals↗