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At least 613 records · Page 34Linked to original sources
PubMed2004

Downregulation of STAT3 activation is required for presumptive rod photoreceptor cells to differentiate in the postnatal retina.

Ciliary neurotrophic factor (CNTF) has been known to inhibit the differentiation of presumptive rod photoreceptor cells; however, the underlying mechanisms have remained to be elucidated. We demonstrated that STAT3 activation, but not SHP2 activation, is responsible for the CNTF/gp130 signaling that inhibits expression of Rhodopsin and its upstream activator, crx, in the retinal explants derived from P0 mice (P0 retinal explants), utilizing STAT3-deficient retina and electroporation of dominant-negative form of STAT3 (STAT3F). We also demonstrated that STAT3 activation in presumptive rod photoreceptor cells at E18.5 is rapidly downregulated at P0, when Rhodopsin expression starts during retinal development. Persistent STAT3 activation in the P0 retinal explants prevented Rhodopsin expression and rapid upregulation of crx expression. STAT3-deficient retinas did not exhibit precocious rod photoreceptor cell differentiation as a whole, although they occasionally exhibited precocious upregulation of crx mRNA. Thus, we conclude that downregulation of STAT3 activation is required, but insufficient, for rod photoreceptor cell differentiation in the postnatal retina.

Animals↗
PubMed1985

Retinal complications following YAG laser capsulotomy.

Eighteen patients (19 eyes) developed retinal complications following YAG laser capsulotomy. Complications included one retinal flap tear, two macular holes, six eyes with cystoid macular edema, and ten retinal detachments. The retinal complications resulted from opening the capsule and were not a specific complication of the YAG laser.

Aged↗
PubMed1992

Detection and maturation of VEP albino asymmetry: an overview and a longitudinal study from birth to 54 weeks.

The genetic anomaly in albinism prevents adequate melanin metabolism within the fetal eye cup and stalk. This results in severe disruption of pre- and postnatal retinal development and the condition of abnormal temporal retinal projections. The obligate misrouting of retinal-geniculate-cortical projections in albinism can be detected in the topographical representation across the occiput of the visual evoked potential (VEP). Age-dependent misrouting detection methods are described which yield 100% detection rates with zero false positives across the life span. By combining appropriate state-defined neonatal recording procedures with the albino infant VEP test paradigm, the presence of aberrant optic pathway projections was observed in a 5-day-old full-term infant. Maximum asymmetry was observed within a long-latency window of the response which shifted during the postpartum period to shorter latencies. Longitudinal studies show two specific latency regions of significant VEP asymmetry. The first occurs within 40-70 ms after stimulus onset and remains constant across the age range. The second, more robust, cluster of asymmetry occurs within a longer latency window and shows an age-related shift towards shorter latencies. The decreasing latency of this asymmetry is concomitant with normal maturational changes of the evoked response. These results show that VEP misrouting can be extended to reliable albino diagnosis within the neonatal period and to the assessment of visual maturation.

Aging↗
PubMed2002

The mineralocorticoid receptor in rodent retina: ontogeny and molecular identity.

PURPOSE: Mineralocorticoid hormones contribute to ion-water balance in all cell types. In this study, we investigated the presence of mineralocorticoid receptors in rat and bovine ocular tissues and during retinal development. METHODS: Isolated photoreceptors and/or intact retina, retinal pigment epithelium (RPE) cells, and ciliary body were analyzed for the expression of MR (Mineralocorticoid Receptor) using the polymerase chain reaction (PCR) technique. Since aldosterone can stimulate the expression of epithelial Na+ channels (ENaC), expression of this gene in RPE was measured under basal and aldosterone-induced level. RESULTS: MR was expressed in rat photoreceptors and in the inner retina (inner nuclear layer and ganglion cell layer) even one day after birth, almost hundred percent identity was observed between rat retina and kidney MR gene products. The expression was also present in the RPE and in the ciliary body. ENaC gene was expressed in RPE and generated a predicted band at 520 bp following RT-PCR amplification which was 95% homology to that of ENaC mRNA from bovine kidney. The incubation of RPE cells in vitro with aldosterone increased the mRNA level of ENaC. CONCLUSIONS: MR expression in the mammalian retina, RPE, and ciliary body extends the potential field of action for mineralocorticoid hormones. Results on RPE cells are consistent with the idea that steroid hormones may regulate the physiology of these tissues by modulating ENaC expression. This study provides new light on the potential effect of mineralocorticoid in this area of the nervous system.

Aldosterone↗
PubMed2003

Gene discovery in the embryonic chick retina.

PURPOSE: The chick embryo is a powerful model system for the study of retinal development. However, analysis of gene expression in the chick retina has lagged behind biological studies. The purpose of this study was to identity and characterize genes expressed in the chick embryo retina as candidate molecules involved in the development and function of photoreceptors and other retinal cell types. METHODS: RNA from embryonic day (ED) 18 White Leghorn chick embryo retinae was used to generate an oligo dT-primed cDNA library. Bacterial colonies representing five thousand individual clones were arrayed onto nylon membranes using a microarray robot. Replicate membranes were hybridized with cDNA probes synthesized from ED 18 retina, brain and liver. Clones that appeared preferentially expressed in retina were identified by homology searches, and their spatial and temporal expression patterns were analyzed by in situ hybridization. RESULTS: Two hundred and seventy-two clones were identified. Approximately forty percent of the clones represented potential novel genes, including ESTs, hypothetical proteins and clones with no assigned identities. Furthermore, many genes were identified that are the putative chick orthologues of genes cloned from other species. We determined the expression pattern of several clones for which sequence homologies suggested possible roles in transcriptional regulation, apoptosis or intercellular signaling. Their corresponding mRNAs were expressed in the embryonic retina in topographically specific, developmentally regulated patterns. CONCLUSIONS: We identified and characterized genes in the chick embryo retina using a combination of microarray analysis and in situ hybridization. Analysis of the expression patterns suggests involvement of several of these genes in key events during embryogenesis.

Animals↗
PubMed1989

[Retinitis in multiple sclerosis].

A 37-year-old man treated since 6 years for multiple sclerosis is described because retinitis developed in an exacerbation of the disease. Retinitis was treated successfully with penicillin and hydrocortisone.

Adult↗
PubMed1980

Herpes virus hominis encephalomyelitis and retinal vasculitis in adults.

The cases of two adults who developed viral encephalomyelitis are presented. The diagnosis of herpes virus hominis infection was made as a result of the rising titers of herpes virus on indirect fluorescence tests in the serum and the cerebrospinal fluid. Both patients developed retinal vasculitis with retinal edema and hemorrhages. The importance of follow-up examinations of the fundus is stressed to avoid rhegmatogenous retinal detachment caused by retinal tears.

Aged↗
PubMed2000

The spatial and temporal expression patterns of netrin receptors, DCC and neogenin, in the developing mouse retina.

Recently it has been demonstrated that the guidance of retinal ganglion cell (rgc) axons through the optic disc is dependent on the DCC/netrin-1 axonal guidance system. To gain further insight into the function of the netrin receptors, DCC and Neogenin, in retinal development we have studied the expression patterns of these receptors in the embryonic mouse retina. Neogenin mRNA was restricted to a single neural cell type, the rgc. However, strong Neogenin mRNA expression was observed in the extending fiber cells of the developing lens suggesting a role for Neogenin in the migration events shaping the early lens. Our studies demonstrated that DCC mRNA was expressed at high levels in chains of closely opposed neurons as they migrated towards the emerging mantle layer in the early retina (E12.5-E13.5) suggesting a role for DCC in the migration of neurons out of the ventricular zone. DCC protein expression was high on rgc axons as they actively navigated through the optic disc into the optic nerve. At birth, when the majority of rgc axons had projected through the optic disc, DCC protein was no longer detectable on the distal axonal segments within the optic nerve despite significant DCC protein expression on the proximal axonal membranes in the nerve fiber layer. These observations suggest that a localized down-regulation of DCC protein occurs on projecting axonal membranes once the DCC guidance function is no longer required. We also demonstrated that DCC mRNA and protein were expressed by amacrine cells and Müller glial cells while DCC mRNA was detected in horizontal cells. Taken together, these expression patterns suggest a role for DCC in axon outgrowth and/or pathfinding for a variety of retinal neurons and in the migration of newly born neurons within the developing retina.

Animals↗
PubMed1996

Retinal ganglion cell axons recognize specific guidance cues present in the deafferented adult rat superior colliculus.

During development, retinal ganglion cell axons establish a topographically ordered projection from the retina to the superior colliculus (SC). The putative guidance activities for retinal axons that operate during embryonic development are not detectable in the normal adult SC. However, these cues reappear upon transection of the optic nerve of adult rats. In the present study, we used a modified version of the "stripe assay," in which membranes from either anterior or posterior SC alternated with laminin stripes. Temporal embryonic retinal axons consistently avoid membranes from embryonic posterior SC, but only rarely from adult deafferented SC. However, they are attracted to membranes from both embryonic and adult deafferented anterior SC. Nasal retinal axons only show a significant preference for membranes from posterior SC after deafferentation. When retinal axons were offered a choice to grow on membranes either from their embryonic or their deafferented target regions, they showed a preference for the deafferented SC. On carpets consisting of laminin and membranes from normal SC (not deafferented) or nontarget regions (inferior colliculus), temporal and nasal axons grow either in a random fashion or show preferences for the laminin stripes. Our modified version of the classic stripe assay shows specific growth preferences of embryonic retinal axons for membrane lanes from their appropriate embryonic or deafferented adult target regions. These findings suggest that the deafferentation of the SC in adult rats triggers the reexpression of specific guidance activities for retinal axons. Those "attractive" guidance cues appear to be differentially expressed in the developing and deafferented SC.

Afferent Pathways↗
PubMedDate not supplied

Effects of ethanol on the inner layers of chick retina during development.

Optic nerve hypoplasia is an important malformation of the fetal alcohol syndrome whose teratogenic mechanisms are unknown. In our experimental model we have quantified the concentration of ethanol and acetaldehyde in the retina and vitreous humor of the developing chick. The effect of ethanol alone during retinal development was analyzed by conventional histological techniques and by immunostaining. A single injection of ethanol in the vitelline sac at the beginning of retinal cell differentiation retarded synaptogenesis in the inner plexiform layer and produced abundant ganglion cell death and a sharp diminution of myelinic axons. Our observations could help to explain certain alterations described in children exposed to ethanol during the development of their nervous system.

Acetaldehyde↗
PubMed1994

Distribution of an endogenous 16-kd S-lac lectin in the chicken retina.

PURPOSE: To examine by indirect immunofluorescence the distribution of an endogenous 16-kd S-lac lectin (soluble lactose binding lectin) during development of the chicken retina. METHODS: Cryosections of retinal tissue at different developmental stages and cultured retinal cells (either not permeabilized or permeabilized with acetone) were incubated with a rabbit antiserum that specifically reacts with the retinal 16-kd S-lac lectin. After incubation with a fluorescent-labeled secondary antibody, tissue sections and cultured cells were analyzed by fluorescence microscopy. RESULTS: Retina was weakly stained with the antiserum on early embryonic day 7, whereas on embryonic days 13 and 18 it showed a restricted "granular" staining in the outer retina. At embryonic day 18, in addition, there was widespread staining in all retinal layers. This pattern was maintained by postnatal day 5 and in the adult retina, although the intensity of the staining of the outer retina was weaker. In retinal cell cultures, glial-like flat cells and monopolar, bipolar, and multipolar neurons were stained with the antiserum, but only if they had been previously permeabilized with acetone. CONCLUSION: The results suggest that the distribution of a 16-kd S-lac lectin changes during retinal development. Cell culture experiments indicate that most often the lectin is localized intracellularly in the different retinal cell types.

Animals↗
PubMed1999

Developmental basis of retinal-specific induction of cancer by RB mutation.

Understanding why children with RB mutations specifically develop retinoblastoma will contribute to the understanding of the fundamental principles of cancer. Only a subset of developing retinal cells are at risk for developing cancer when RB is mutant because rod photoreceptor and bipolar cells never normally express RB. Retinoblastomas are observed to arise commonly in the inner nuclear layer, where they can show features attributed to outer nuclear layer cells (photoreceptors). The best-studied function of RB is control of the cell cycle, and the usual tissue consequence of loss of RB is apoptosis. Perhaps the specificity of RB mutation for retinal cancer resides in the dependency of this tissue on programmed cell death to achieve a precise architecture of individual types of interconnecting neurons. The additional mutations that are present in all retinoblastoma, such as the i(6p) marker chromosome, may interrupt signals that normally would induce apoptosis when RB is absent. A combination of loss of cell cycle control and loss of signals that delete extra cells would result in retinoblastoma.

Animals↗
PubMed1986

Prevalence and development of retinopathy in children and adolescents with type 1 (insulin-dependent) diabetes mellitus. A longitudinal study.

In 231 subjects with Type 1 diabetes mellitus aged 17.6 +/- 4.0 years, with a diabetes duration of 8.5 +/- 4.9 years at the end of the study, the prevalence and the development of retinopathy during a period of 5 years were studied. All patients were examined between one and six times both by ophthalmoscopy and fluorescein angiography. A total of 626 fluorescein angiographies were evaluated. By the end of the study, 109 out of 231 patients (47%) had developed retinal changes, half of which were classified as minimal (less than 5 microaneurysms). Thirty-eight patients (35% of those affected) had background (n = 28) or proliferative (n = 10) retinopathy. In subjects less than 15 years of age and diabetic for less than 5 years, retinal lesions were rare. With increasing age and duration of diabetes, both the prevalence and severity of retinal changes increased markedly. Life-table analysis was used to calculate the median individual risk for the development of early retinal changes, which was 9.1 years of diabetes duration. This risk differed in sub-groups with different ages at onset of diabetes, i.e. 12.1, 8.9 and 6.6 years (p less than 0.0001), with diabetes starting below 4, between 5 and 9, and after 10 years of age respectively. After 18 years of diabetes, every patient demonstrated at least incipient structural changes. Fluorescein angiography allowed the detection of retinopathy, on average, four years earlier than with ophthalmoscopy. The median interval between the 'onset' of retinopathy, as indicated by a few microaneurysms, and background retinopathy was 5 years.

Actuarial Analysis↗
PubMed2002

Local and target-derived brain-derived neurotrophic factor exert opposing effects on the dendritic arborization of retinal ganglion cells in vivo.

The dendritic and axonal arbors of developing retinal ganglion cells (RGCs) are exposed to two sources of BDNF: RGC dendrites are exposed to BDNF locally within the retina, and RGC axons are exposed to BDNF at the target, the optic tectum. Our previous studies demonstrated that increasing tectal BDNF levels promotes RGC axon terminal arborization, whereas increasing retinal BDNF levels inhibits RGC dendritic arborization. These results suggested that differential neurotrophic action at the axon versus dendrite might be responsible for the opposing effects of BDNF on RGC axonal versus dendritic arborization. To explore this possibility, we examined the effects of altering BDNF levels at the optic tectum on the elaboration of RGC dendritic arbors in the retina. Increasing tectal BDNF levels resulted in a significant increase in dendritic branching, whereas neutralizing endogenous tectal BDNF with function-blocking antibodies significantly decreased dendritic arbor complexity. Thus, RGC dendritic arbors react in opposing manners to retinal- versus tectal-derived BDNF. Alterations in retinal BDNF levels, however, did not affect axon terminal arborization. Thus, RGC dendritic arborization is controlled in a complementary manner by both local and target-derived sources of BDNF, whereas axon arborization is modulated solely by neurotrophic interactions at the target. Together, our results indicate that developing RGCs modulate dendritic arborization by integrating signals from discrete sources of BDNF in the eye and brain. Differential integration of spatially discrete neurotrophin signals within a single neuron may therefore finely tune afferent and efferent neuronal connectivity.

Animals↗
PubMed2005

Analysis of the Zebrafish perplexed mutation reveals tissue-specific roles for de novo pyrimidine synthesis during development.

The zebrafish perplexed mutation disrupts cell proliferation and differentiation during retinal development. In addition, growth and morphogenesis of the tectum, jaw, and pectoral fins are also affected. Positional cloning was used to identify a mutation in the carbamoyl-phosphate synthetase2-aspartate transcarbamylase-dihydroorotase (cad) gene as possibly causative of the perplexed mutation and this was confirmed by gene knockdown and pyrimidine rescue experiments. CAD is required for de novo biosynthesis of pyrimidines that are required for DNA, RNA, and UDP-dependent protein glycosylation. Developmental studies of several vertebrate species showed high levels of cad expression in tissues where mutant phenotypes were observed. Confocal time-lapse analysis of perplexed retinal cells in vivo showed a near doubling of the cell cycle period length. We also compared the perplexed mutation with mutations that affect either DNA synthesis or UDP-dependent protein glycosylation. Cumulatively, our results suggest an essential role for CAD in facilitating proliferation and differentiation events in a tissue-specific manner during vertebrate development. Both de novo DNA synthesis and UDP-dependent protein glycosylation are important for the perplexed phenotypes.

Animals↗
PubMed2005

Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells.

Retinal and macular degenerations are a major cause of blindness. Cell transplantation is a possible therapeutic approach for the replacement of degenerating retinal cells. Here, we studied the potential of human embryonic stem cells (hESCs) to survive, integrate, and differentiate into retinal cells after intraocular transplantation. Highly enriched cultures of neural precursors (NPs) expressing transcripts of key regulatory genes of retinal development were developed from the hESCs. After spontaneous differentiation in vitro, the NPs gave rise to progeny expressing markers of retinal progenitors and photoreceptor development, though this was uncommon and cells expressing markers of mature photoreceptors were not observed. After transplantation into rat eyes, the NPs survived for 16 weeks, migrated large distances, and integrated in the host retina. Teratoma tumors were not observed. Human cells expressing rhodopsin, blue cone opsin, and neural retina leucine zipper transcription factor were observed in subretinal grafts, but not within vitreal and inner retinal grafts. The results suggest that hESCs have the potential to differentiate into retinal cells and that the subretinal microenvironment supports their differentiation toward a photoreceptor fate. This may be the first step toward further developments that eventually may allow the use of hESCs for transplantation in retinal degenerations.

Animals↗
PubMed2006

Development of the neural retina and its vasculature in the marmoset Callithrix jacchus.

The morphological sequence of retinal development in the New World marmoset monkey Callithrix jacchus is similar to previous reports in Macaca and humans. The incipient fovea is present at fetal day (Fd) 100 as the only part of the retina that contains five distinct layers, including a single layer of cone photoreceptors. A foveal pit begins to form at Fd 135 in the center of the foveal avascular zone which is surrounded by a ring of blood vessels (BV) and astrocytes. At birth (Fd 144) the fovea has a single layer of cones over the pit center where the inner retinal layers are thinned but still separated. After birth the fovea rapidly matures so that foveal cone and pit morphology are similar to adult by 4 months. Five distinct layers and the BV plexus in the nerve fiber layer are present to the retinal edge in neonatal marmosets. Near the optic disc BV are sprouting into outer retinal layers at birth and vascularization of the outer retina is completed by 2 to 3 months. Retinal length increases sharply up to Fd 135, but undergoes a quiescent period around birth during which pit formation begins. Length then increases again up to 4mo, followed by a slow increase into adulthood. The postnatal increase is accompanied by a marked thinning of the peripheral retina. The pars plana appears after birth and its length increases at least until 2 years of age. The major difference between marmoset and Macaca is the relative immaturity of the marmoset fovea at birth, and its rapid development after birth. This makes the marmoset a good candidate for neonatal experimental manipulation of retinal and eye development.

Animals↗
PubMed1992

Coordinate expression of insulin-like growth factor system components by neurons and neuroglia during retinal and cerebellar development.

The interactions of insulin-like growth factors (IGFs) with the type I IGF receptor are modulated by a family of high-affinity IGF binding proteins (IGFBPs). One of these, IGFBP2, demonstrates a striking spatiotemporal relationship with IGF-I during cerebellar and retinal development. IGF-I mRNA is transiently expressed in large projection neurons--cerebellar Purkinje and retinal ganglion cells--while IGFBP2 mRNA is selectively expressed by contiguous neuroglia--Bergmann glia in the cerebellum and Müller cells and astrocytes of the nerve fiber layer in the retina. IGF-I and IGFBP2 gene expression is not only neuroanatomically coordinated but also temporally synchronized, peaking together during the postnatal maturation of these structures. This pattern of IGF system expression suggests that IGFBP2 is closely related to IGF-I's action in the developing nervous system.

Aging↗