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Localization of a fatty acid binding protein and its transcript in the developing chick retina.

The undifferentiated chick retina has elevated levels of fatty acid binding protein (R-FABP) mRNA. Tissue maturation is accompanied by a 50-100-fold decrease in transcript levels. To determine the location of the R-FABP transcript and its encoded protein in the developing retina, in situ hybridization and immunohistochemical analyses were carried out using chick embryos at different stages of development. The R-FABP mRNA and protein were found throughout the retina from day 3 to day 7 of incubation. Accumulation of R-FABP in the neurites of ganglion cells could readily be detected at early developmental stages. By day 11, R-FABP transcript levels were considerably reduced in the retina, while the protein was primarily found in the inner nuclear layer, inner plexiform layer and optic nerve fiber layer of the retina. As well, R-FABP mRNA and protein were abundant in the non-pigmented ciliary epithelium, which represents the forward prolongation of the retina in the anterior eye. Immunoelectron microscopy revealed the presence of R-FABP in both the nucleus and cytoplasm of day 4 retinal cells. In the day 13 retina, R-FABP was abundant in the processes of neuronal cells. These results suggest that, early in retinal development, there is a requirement for FABP in the nucleus as well as the cytoplasm of all retinal cells. At later stages, the concentration of R-FABP in the processes of neuronal cells would suggest a biochemical or structural role related to neurite extension and synapse formation.

Animals↗

Docosahexaenoate metabolism and fatty-acid composition in developing retinas of normal and rd mutant mice.

The fatty-acid composition of retinal lipids in developing control and rd mice (C57BL/6J) was determined. In addition, fatty-acid composition in brain and retina of normal and rd adult animals was compared. At 11 days of postnatal age, rd retinas contained proportionally less docosahexaenoate than controls, whereas the reverse relationship held for oleate at 20 days of age. In contrast, no differences in the fatty-acid composition of brain lipids were observed between rd and control animals. We also examined docosahexaenoate metabolism in rd and control retinas of different postnatal ages in vitro. These studies of [1-14C]docosahexaenoic-acid incorporation into retinal phospholipids and neutral lipids demonstrated significantly higher incorporation into triacylglycerols of the rd retina, beginning at 14-15 days of postnatal age. Incorporation into diacylglycerols and phospholipids was also higher in rd retinas than in controls at 14 days of age and older. Moreover, the concentration of ganglioside (a glycolipid class probably enriched within inner retinal layers) was higher in adult rd retinas. Degeneration of the rd retina can be detected histologically as early as 8-9 days. Therefore, the alterations of fatty-acid composition and docosahexaenoate metabolism described here are probably an effect, rather than a cause, of retinal degeneration in the rd mouse.

Aging↗

Age-related alterations in vitamin A metabolism in the rat retina.

Vitamin A plays a central role in visual transduction and in maintaining the structural integrity of the retina. It is possible that age-related alterations in vitamin A metabolism in the eye could contribute to the impairment of visual function that occurs during senescence. Therefore, investigations were conducted to determine whether the metabolism of this vitamin in the rat retina was altered during aging. Pigmented rats aged 12-, 22-, and 32 months were dark-adapted, and one eye from each animal was enucleated under dim red light. The neural retinas were separated from the retinal pigment epithelium (RPE)-choroid-scleral complexes, and the amounts and forms of vitamin A in both tissues were determined. The animals were then fully light-adapted, and the same measurements were performed on the tissues from the remaining eye of each rat. A number of age-related alterations in the vitamin A composition and content of the retina and RPE were observed. The most pronounced of these changes were significant increases in the ratios of retinyl palmitate to retinyl stearate with advancing age in both the neural retina and RPE. The total vitamin A ester contents of the RPEs increased during senescence in the dark-adapted state, but not in the light-adapted state. Retinyl ester levels in the neural retinas, on the other hand, did not differ significantly between 12- and 32-month-old animals in either the light-adapted or dark-adapted states. The amounts of all-trans retinol in the neural retinas decreased during aging, mainly in the dark-adapted state, whereas aging had no influence on RPE all-trans retinol content. The age-related alterations in metabolism of vitamin A that these observations reflect may be related to certain changes in visual function that occur during senescence.

Adaptation, Ocular↗

Cyclic GMP-phosphodiesterase of rd retina: biosynthesis and content.

Deficient cGMP-phosphodiesterase (cGMP-PDE) activity results in elevated levels of cGMP in the rd retina before any pathological signs are observed. Since the enzyme is present in rd retina, although it is barely activated by light, we determined whether its synthesis starts at the same time as that of cGMP-PDE in normal retina, or if either its synthesis is halted or degradation of the enzyme increases before the degeneration of the visual cells. We found that synthesis of cGMP-PDE in rd retina is comparable with that in normal retina while the photoreceptors are viable but that cGMP-PDE content is lower than that of normal retina before the visual cells begin to degenerate. Our results suggest that cGMP-PDE is more susceptible to degradation in rd than in normal photoreceptors or, alternatively, that proteolytic enzyme(s) involved in the degradation of cGMP-PDE are in higher concentration or more active in the defective than in the normal retina.

3',5'-Cyclic-GMP Phosphodiesterases↗

Stem cells in the teleost retina: persistent neurogenesis and injury-induced regeneration.

The retina of the adult teleost fish is an important model for studying persistent and injury-induced neurogenesis in the vertebrate central nervous system. All neurons, with the exception of rod photoreceptors, are continually appended to the extant retina from an annulus of progenitors at the margin. Rod photoreceptors, in contrast, are added to differentiated retina only from a lineage of progenitors dedicated to making rods. Further, when the retina is lesioned, the lineage that produces only rods ceases this activity and regenerates retinal neurons of all types. The progenitors that supply neurons at the retinal margin and rod photoreceptors and regenerated neurons in the mature tissue originate from multipotent stem cells. Recent data suggest that the growth-associated neurogenic activity in the retina is regulated as part of the growth hormone/insulin-like growth factor-I axis. This paper reviews recent evidence for the presence of stem cells in the teleost retina and the molecular regulation of neurogenesis and presents a consensus cellular model that describes persistent and injury-induced neurogenesis in the retinas of teleost fish.

Animals↗

Transplantation of ocular stem cells: the role of injury in incorporation and differentiation of grafted cells in the retina.

The incorporation of transplanted cells into the host retina is one of the prerequisites for successful cell replacement therapy to treat retinal degeneration. To test the hypothesis that injury promotes cell incorporation, stem cells/progenitors were isolated from the retina, ciliary epithelium or limbal epithelium and transplanted into the eyes of rats with retinal injury. Different stem cell/progenitor populations incorporated into traumatized or diseased retina but not into the normal retina. The proportion of cells incorporated into the inner retina was consistently higher than in the outer retina. The transplanted cells expressed markers specific to cells of the lamina into which they were incorporated suggesting that cues for specific differentiation are localized within the inner and outer retina. These findings demonstrate that injury-induced cues play a significant role in promoting the incorporation of ocular stem cells/progenitors regardless of their origin or their differentiation along specific retinal sublineage.

Animals↗

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

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

Animals↗

Neurotrophin receptors (Trk A, Trk B, and Trk C) in the developing and adult human retina.

In this study, the ontogeny and distribution patterns of three neurotrophin receptors (Trk A, Trk B, and Trk C) were examined in the human retinas. Immunohistochemistry was performed on sections of retina and optic nerve from fetuses (11-24 weeks of gestation, wg), one infant (4-month-old) and two adult (35- and 65-years-old) subjects. At 11 wg, Trk A was expressed in the nerve fiber and inner plexiform layers, while Trk B and Trk C were expressed in many neuroblastic cells. By 16-17 wg, the photoreceptors showed immunoreactivity for all three receptors. The ganglion cell layer and amacrine cells were conspicuously immunoreactive for Trk A and Trk C, but labeled diffusely for Trk B. The horizontal cells were labeled for Trk A and Trk B. The pattern was same in the retinas at midgestation (20-21 wg). Shortly after this period, there was an apparent decrease in receptor immunoreactivity in the fetal retinas. In the infant retina, Trk A immunoreactivity was absent from horizontal cells. The photoreceptors were immunopositive for Trk B and Trk C, in infant and adult retinas. In the adults, few cells of the ganglion cell layer and inner nuclear layer were clearly labeled for Trk A and Trk C, and diffusely for Trk B. The glial cells of the retina and optic nerve immunoreacted for Trk A only, right from fetal 16 wg. The early expression of Trk B and Trk C on neuroblastic cells suggests that both play a role in cell proliferation. The developmental distribution pattern of Trk A, on the other hand, provides evidence for its involvement in differentiation of the inner plexiform layer, horizontal cells and neuroglia. The results strongly suggest that photoreceptor development is mediated by Trk receptors. The novel localization of Trk B and Trk C on adult photoreceptors points to a possible therapeutic potential for BDNF and NT-3, respectively, in photoreceptor diseases.

Adult↗

Tissue oxygen levels control astrocyte movement and differentiation in developing retina.

Astrocytes play a key role in the development of retinal vessels by detecting hypoxia in developing retina and secreting the hypoxia-induced angiogenic factor VEGF to induce vessel formation. The astrocytes which play this role are themselves spreading over the retina, just ahead of the growing vessels. To understand the mechanisms which keep astrocytes in this strategic 'just ahead' position we have studied the effects of hyperoxia and hypoxia on astrocyte differentiation and movement in situ in neonatal rat retina and in primary culture. Hyperoxia in situ inhibited the stellation of astrocytes, so that they persisted in a relatively unbranched form, which accumulated at the edge of their spreading population; hyperoxia permitted but did not accelerate migration. Conversely, hypoxia induced unstellated astrocytes to stellate within 6 h. If the hypoxia was abnormally severe, it caused the astrocytes to hyperstellate and slowed their spread. Astrocytes in primary culture did not change morphology or motility when challenged by hypoxia. When treated with medium conditioned by retina however, astrocytes became mobile and, if the medium was conditioned by hypoxic retina, became stellate. These results suggest that the oxygen released by retinal vessels maintains the mobility of astrocytes, via a diffusible factor released by other retinal cells. Conversely, naturally generated hypoxia of developing retina plays a triple role, inducing astrocytes to stellate, to end their migration and to produce VEGF, thereby inducing vessel formation. The induction of stellation is mediated by a diffusible factor released by other retinal cells. Thus hypoxia of the retina generated by neural maturation induces key events in both the differentiation of astrocytes and the formation of blood vessels.

Aging↗

Effects of nitric oxide, light adaptation and APB on spectral characteristics of H1 horizontal cells in carp retina.

The spectral characteristics of cone-driven horizontal cells of H1 subtype (H1 HCs) receiving main synaptic input from red-sensitive cones were studied in light- and dark-adapted retinae of carp. The spectral sensitivity profile of H1 HCs in dark-adapted retinae was practically the same as the absorption spectrum of red-sensitive cones. Light-adaptation decreased the sensitivity preferentially in the short-wavelength (blue/green) region, resulting in a relative enhancement of the 617 nm peak. Application of nitric oxide (NO) donors, sodium nitroprusside (SNP) and S-nitrosoglutathione (SNOG or GSNO), or dopamine to dark-adapted retinae decreased the sensitivity preferentially in blue/green region, an effect similar to that of light-adaptation. Application of haemoglobin (Hb, an NO scavenger) or 2-amino-4-phosphonobutyrate (APB, a metabotropic glutamate receptor agonist), to light-adapted retinae increased the sensitivity preferentially in the blue/green region, an effect similar to dark-adaptation. The photoresponses of H1 HCs were univariant in dark-adapted retinae as well as Hb-treated light-adapted retinae. In light-adapted retinae with normal Ringer, however, the univariance did not hold. These results suggested that the photoresponses of H1 HCs to short-wavelength stimuli contain a depolarising (sign-reversing) component, which can be activated by light-adaptation or application of NO and dopamine, and inactivated by dark-adaptation or deprivation of NO or application of APB.

Adaptation, Ocular↗

Differential expression of beta-amyloid precursor and Bcl-2 proto-oncogene proteins in the developing dog retina.

Previous studies of rat retinas have not only provided evidence that beta-amyloid precursor (APP) and B-cell lymphoma proto-oncogene (Bcl-2) proteins are colocalized in retinal Müller glial cells, but have also indicated that common mechanisms regulate their expression in these cells (Chen, S.T., Garey, L.J., Jen, L.S., 1994. Bcl-2 proto-oncogene protein immunoreactivity in normally developing and axotomised rat retinas. Neurosci. Lett. 172, 11 14; Chen, S.T., Gentleman, S.M., Garey, L.J., Jen, L.S., 1996. Distribution of beta-amyloid precursor and B-cell lymphoma proto-oncogene proteins in the rat retina after optic nerve transection or vascular lesion. J. Neuropathol. Exp. Neurol. 55, 1073-1082; Chen, S.T., Garey, L.J., Jen, L.S., 1997. Expression of beta-amyloid precursor protein immunoreactivity in the retina of the rat during normal development and after neonatal optic tract lesion. NeuroReport 8, 713-717). This investigation attempts to resolve whether or not the pattern observed in rats also applies to other higher mammalian species by examining the expression of immunoreactivity to APP and Bcl-2 in developing as well as mature dog retinas using immunocytochemical methods. Experimental results indicate that the immunoreactivity of both APP and Bcl-2 is located primarily in the inner retina, particularly in the ganglion cells and their axons in late fetal and neonatal stages. From the second postnatal week (the time of eye opening) onwards, immunoreactivity to APP, but not Bcl-2, is localized primarily in the endfeet and proximal part of the radial process of retinal Müller glial cells. Although the findings show both APP and Bcl-2 are expressed in ganglion cells and their processes suggest that the molecules have a role in the differentiation of neurons in the central nervous tissue, the lack of Bcl-2 in the Müller glial cells in dog retinas further suggests that the two molecules may have different biological roles with respect to glial function.

Amyloid beta-Protein Precursor↗

Expression of functional N-methyl-D-aspartate receptors during development of chick embryo retina cells: in vitro versus in vivo studies.

The N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors were studied in retina cells developing in chick embryos and in retina cells cultured as retinospheroids, at the same stages of development. In the retinospheroids, the activity of the NMDA receptors was followed by monitoring the changes in the intracellular free calcium concentration ([Ca2+](i)), in response to NMDA or to L-glutamate. The expression of the subunits NMDAR1, NMDAR2A/B and NMDAR2C in the retinospheroids and in chick retinas were determined by Western blot analyses. The changes in [Ca2+](i) in response to 400 microM NMDA increased from 5 h in vitro to 3 days in vitro (DIV) and remained constant until 14 DIV, whereas the [Ca2+](i) response to 500 microM L-glutamate increased from 5 h in vitro to 3 DIV and decreased slightly until 14 DIV. In the retinospheroids, the expression of the NMDAR1 and NMDAR2A/B subunits increased from 5 h in vitro until 14 DIV, whereas the NMDAR2C subunit increased from 5 h in vitro until 10 DIV and remained constant until 14 DIV. In the retinas, the expression of NMDAR1 increased from embryonic day 8 (E8) until E15, decreased until E18, and increased again until day 22 (post-hatched 1, PH1). The NMDAR2A/B increased from E8 until E18 and decreased slightly until PH1, whereas the NMDAR2C subunit increased from E8 until E15, remained constant until E18, and increased again until PH1. The results suggest that NMDA receptors are expressed and functionally active at early embryonic stages in the retina and in retinospheroids, before synapse formation (E12). However, the calcium responses to NMDA were relatively constant from 3 DIV until 14 DIV, showing no correlation with the increase in the expression of the studied NMDA receptor subunit during the same period. Also, the patterns of NMDA receptor subunits expressed in chick embryo retina cells cultured in vitro and in retina cells developing in vivo were similar.

Animals↗

Melatonin receptor RNA expression in Xenopus retina.

Melatonin is an indolamine hormone presumably synthesized by retinal photoreceptors, and may act as a paracrine signal of darkness within the retina. Previous studies have suggested that melatonin, acting through specific receptors, may be involved in cyclic retinal functions such as photoreceptor outer segment disc shedding and phagocytosis, and modulation of neurotransmitter release in the inner retina. The goal of this study was to determine if melatonin receptor mRNA is expressed in the neural retina and retinal pigment epithelium (RPE) of Xenopus laevis. Sheets of RPE, devoid of contaminating cells, were obtained from Xenopus eyes, and epithelial cultures were subsequently established on microporous membrane filters in a defined medium. Total RNA was isolated from whole brain, neural retina, fresh RPE sheets, and cultured RPE cells. RNA expression of the three known Xenopus melatonin receptor subtypes (MEL1A, 1B, and 1C) was determined by reverse-transcription/polymerase chain reaction (RT/PCR) amplification, followed by Southern hybridization with RNA probes. PCR-amplified cDNA encoding melatonin receptor subtypes 1B and 1C, but not 1A, were detected in reverse-transcribed RNA obtained from brain, neural retina and RPE. RPE cells grown in culture for two weeks also demonstrated 1B and 1C receptor RNA expression. This study suggests that RNA encoding the 1B and 1C melatonin receptor subtypes is expressed in the neural retina and RPE of Xenopus retina, and the expression persists in RPE cells when grown in culture. The expression of melatonin receptor RNA in the RPE may reflect a regulatory role for melatonin in some diurnal events that occur in this tissue, such as phagocytosis of photoreceptor outer segment membranes, and intracellular migration of pigment granules.

Animals↗

Immunohistochemical localization of taurine in the retina of developing and adult human and adult monkey.

The localization of taurine in the retina of fetal (12-25 weeks of gestation), postnatal (five-month-old infant) and adult human (35- and 65-year-old) was examined by immunohistochemistry. Additionally, retinas of fresh adult monkey, which served as positive controls, were employed. No immunoreactivity was found in the fetal retinas from 12-15 weeks of gestation. At 1617 weeks of gestation, the ganglion cells and some of their axons were conspicuously labelled for taurine. At 18-19 weeks, Muller glial endfeet, the inner plexiform layer, some amacrine and putative horizontal cells and photoreceptors showed moderate immunoreactivity. With further development at 20-21 and 24-25 weeks of gestation, the immunoreactivity was prominent in Muller cell endfeet, some bipolar cells and in horizontal cells that were aligned in a row in the inner nuclear layer, close to the fovea. At both fetal stages, the photoreceptors and horizontal cells showed strong immunoreactivity. In the postnatal infant retina, taurine immunoreactivity was present in some amacrine cells and photoreceptor inner segments and nuclei, but not in ganglion and horizontal cells, which was also the pattern noted in the adult monkey and human retinas. With development, a shift in the intensity of taurine immunoreactivity was noted towards the outer retina. The expression of taurine immunoreactivity in most fetal retinal neurons implies a role for this amino acid in the normal development as well as maturation of human retina.

Adult↗

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

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

Adaptation, Ocular↗

Expression of AMPA/kainate receptors during development of chick embryo retina cells: in vitro versus in vivo studies.

The activity and the subunit expression of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate ionotropic glutamate receptors were studied in retina cells developing in chick embryos and in retina cells cultured as retinospheroids, at the same stages of development. In the retinospheroids, the activity of the AMPA/kainate receptors was monitored by following the changes in the intracellular free calcium concentration ([Ca(2+)](i)), in response to AMPA, kainate or to L-glutamate, and the expression of the receptor subunits GluR1, GluR2/3, GluR4 and GluR6/7 was determined in the retinospheroids and in chick retinas by immunodetection using polyclonal antibodies. The changes in [Ca(2+)](i) in response to 400 microM kainate increased from 5h in vitro to 3 days, and remained constant until day 14, whereas the [Ca(2+)](i) in response to 500 microM L-glutamate or 400 microM AMPA increased from 5h in vitro to 3 days, and thereafter decreased slightly until day 14. The [Ca(2+)](i) responses to kainate are mainly due to AMPA receptor stimulation, since the signals were abolished by LY303070, the AMPA receptor antagonist, and were not affected by MK-801, the NMDA receptor antagonist. In retinospheroids, the levels of expression of GluR1 subunit increased from 5h in vitro until day 7, then decreased until day 14. The levels of expression of GluR2/3 and GluR4 subunits increased from 5h in vitro until day 10, and remained constant until day 14. The levels of kainate receptor subunits GluR6/7 increased from 5h in vitro until day 3, and thereafter decreased slightly until day 14. In the retinas, the expression of GluR1 and GluR6/7 subunits increased from day 8 until day 15, and then decreased until day 22 (post-natal 1). The subunits GluR2/3 and GluR4 increased from day 8 until day 18, and remained constant until day 22. The results suggest that AMPA/kainate receptors are expressed at early embryonic stages, although at low levels and before synapse formation (E12). However, the AMPA receptors are not completely functional at the first stage studied since they do not respond to the agonist AMPA. Also, the patterns of AMPA/kainate receptor subunit expression in retinospheroids of chick embryo retina cells cultured in vitro and in retina cells developing in the embryo (in vivo) were similar, indicating that the AMPA/kainate receptor subunits expression in these primary cultures mimics their expression in the developing chick retina.

Animals↗

Persistent neurogenesis in the teleost retina: evidence for regulation by the growth-hormone/insulin-like growth factor-I axis.

Based on results from previous studies (J. Comp. Neurol. 394 (1998) 386, 395), it was hypothesized that the persistent neurogenesis in the retina of teleost fish is modulated by insulin-like growth factor-I (IGF-I), which, in turn, is regulated by growth hormone (GH). Two approaches were undertaken to test this hypothesis. First, a variety of techniques were used to determine if IGF-I and the IGF-I receptor (IGF-IR) are expressed in the retina. Second, GH was injected into animals to stimulate IGF-I synthesis in target tissues, and IGF-I expression and cell proliferation in the retina was quantitatively assayed. Reverse transcriptase-polymerase chain reaction, screening a retinal cDNA library and Northern analysis showed that genes encoding IGF-I and IGF-IR are expressed in the retina of goldfish. In situ hybridization showed that IGF-IR is expressed by retinal progenitors and all differentiated retinal neurons. Intraperitoneal injections of GH elevate IGF-I mRNA levels in the liver, brain and retina and produce a dose-dependent change in the proliferation of stem cells and progenitors in the retina. These data indicate that the principal components of the IGF-I signaling cascade are present in the retinas of teleosts, and we suggest these elements mediate the persistent, growth-associated neurogenesis in this tissue.

Amino Acid Sequence↗

Blood supply to the retina in the laboratory shrew (Suncus murinus).

The blood supply to both retinae was studied light microscopically and by scanning electron microscopy in 48 adult laboratory shrews (Suncus murinus) of both sexes. Thirty-eight of the animals were injected into the left ventricle with Neoprene latex (Du Pont. 601A) or with Mercox (Dai Nippon Ink Ltd., CL-2R) to elucidate the blood supply to the retina from the ophthalmic artery. The remaining animals were kept for histological study of the retina. The central retinal artery, originating from the ophthalmic artery in the muscular part of the orbit, enters the optic nerve, passes through the optic disk together with the central retinal vein and penetrates the vitreous space (cavity of the eye) between the lens and the inner limiting membrane of the retina, where it divides into the dorsal, ventral, and caudal branches. Each branch, moreover, bifurcates into nasal and temporal arterioles and is distributed throughout the retina on the inner limiting membrane as far as the ciliary body and the lens. On the way they obliquely send small vessels through the inner limiting membrane into the outer plexiform layer of the retina. Their vascularization appears to correspond to the membrana vasculosa retinae found in teleosts, amphibia and reptiles.

Animals↗