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At least 1,297 records · Page 72Linked to original sources
PubMed2000

Two secreted retinal factors regulate different stages of development of the outer blood-retinal barrier.

The retinal pigment epithelium (RPE) lies at the interface between the neural retina and the choriocapillaries where it forms a blood-retinal barrier. Like endothelial regions of the blood-brain barrier, the development of the RPE barrier is a gradual, multistep process. A culture model of chick RPE was used to study this development. The permeability of the tight junctions that limit diffusion between neighboring RPE cells was measured as the transepithelial electrical resistance (TER). Embryonic day 14 (E14) retinas were used to make a conditioned medium that lowered the permeability of cultured RPE. The TER of cultures prepared from E14 RPE was twice that of E7 RPE. In each culture, retinal conditioned medium increases the TER 2-2.5 fold. The active factors of conditioned medium that affected each culture had different physical properties. The factor that affected E7 was protease-resistant with a Mr<10 kDa, but the factor that affected E14 appeared to be a protein of approximately 49 kDa. Unlike the effect of astrocyte conditioned medium on endothelia, retinal conditioned medium did not act synergistically with cAMP. These data indicate that the chick retina, which lacks astrocytes, uses different diffusible factors to regulate different stages of tight junction development.

Adrenergic Agonists↗
PubMed1994

Temporal distribution, localization and metabolism of all-trans-retinol, didehydroretinol and all-trans-retinal during Xenopus development.

Recently, the temporal and spatial distribution patterns of the retinoid receptor ligands 9-cis-retinoic acid and all-trans-retinoic acid were described in Xenopus embryos during early development [Creech Kraft, Schuh, Juchau and Kimelman (1994) Proc. Natl. Acad. Sci. U.S.A., in the press]. The present study demonstrates the presence and distribution of their likely precursors, all-trans-retinol, didehydroretinol, didehydroretinal and all-trans-retinal, as well as the occurrence of 4-oxo metabolites, in Xenopus embryos. The temporal and spatial distribution patterns of all-trans-retinol, didehydroretinol and all-trans-retinal did not coincide with that observed for 9-cis-retinoic acid but, in certain regards, were similar to the patterns delineated for all-trans-retinoic acid and all-trans-retinoyl beta-glucuronide. Evidence is presented that 9-cis-retinoic acid can be synthesized from both all-trans-retinoic acid and all-trans-retinol in Xenopus embryos, suggesting that the difference between the distributions of 9-cis-retinoic acid and the other retinoids may be caused by selective synthesis and/or protein binding of the 9-cis isomer.

Animals↗
PubMed2001

Modeling temporal behavior of postnatal cat retinal ganglion cells.

During development, mammalian retinal ganglion cells (RGCs) go through marked ontogenetic changes with respect to their excitable membrane properties. Voltage-clamp studies conducted in our laboratory have shown that the amplitude, voltage-dependence and kinetics of activation and inactivation (where present) of Na(+), K(+) and Ca(2+) conductances all exhibit developmental changes during a time when the firing patterns of mammalian ganglion cells shift from being transient to being predominantly sustained in nature. In order to better understand the contribution of each conductance to the generation of spikes and spiking patterns, we have developed a model based on our experimental data. For simplicity, we have initially used experimental data obtained from postnatal ganglion cells. At this age the ontogenetic changes observed in the characteristics of the various ionic currents are complete. Utilizing the methods adopted by Hodgkin and Huxley for the giant squid axon, we have determined rate equations for the activation and inactivation properties of the I(A), I(K dr), I(Na), I(Ca L), I(Ca N), and I(leak) currents in postnatal cat RGCs. Combining these with a simplified model of the calcium-activated potassium current (I(KCa)), we have solved and analysed the resulting differential equations. While spikes and spiking patterns resembling experimental data could be obtained from a model in which [Ca(2+)i] was averaged across the whole cell, more accurate simulations were obtained when the diffusion of intracellular Ca(2+) was modeled spatially. The resulting spatial calcium gradients were more effective in gating I(KCa), and our simulations more accurately matched the recorded amplitude and shape of individual spikes as well as the frequency of maintained discharges observed in mammalian postnatal RGCs.

Action Potentials↗
PubMedDate not supplied

Immunologic privilege evoked by histoincompatible intracameral retinal transplants.

In order to examine the fate of intraocular retinal transplants, we placed histoincompatible neural retinas from neonatal BALB/c mice into the anterior chamber (AC) or subconjunctival space of eyes of adult C57BL/6 mice. Clinical and histologic examinations revealed that grafts of developing neural retinal tissue placed within the AC acquired a blood supply, and differentiated into histologically recognizable retinal structures; there was no evidence of inflammation or rejection. By contrast, developing neural retinal allografts placed in the subconjunctival space failed to thrive, and were promptly rejected within 8 days. To examine the nature of the systemic immune response of mice bearing intracameral retinal allografts, C57BL/6 mice, bearing neural retinal allografts from BALB/c donors in their AC for 12 days, were tested for delayed hypersensitivity. When ear challenged with (C57BL/6 x BALB/c)F1 spleen cells, these mice failed to mount significant ear swelling responses, whereas a positive control group of C57BL/6 mice that received neonatal BALB/c retinas implanted in the subconjunctival space displayed vigorous BALB/c-specific delayed hypersensitivity. It is pertinent that, shortly after ear challenge with (C57BL/6 x BALB/c)F1 cells, the previously healthy AC retinal allografts underwent regression and degeneration. Finally, we showed that the spleens of C57BL/6 mice bearing healthy intraocular developing retinal allografts contained suppressor lymphocytes that were revealed in adoptive transfer assays. We conclude that immune privilege is extended to histoincompatible developing retinal transplants placed in the AC of the eye, and that these allografts induce a deviant systemic immune response characterized by impaired expression of delayed hypersensitivity and generation of splenic suppressor cells. We infer that the success of these transplants, compared to similar grafts which are rejected in the subconjunctival space, is predicated upon, and mediated by, the induction of active specific suppression of cell-mediated immunity.

Animals↗
PubMed1993

Glutamate and taurine uptake by retinal pigment epithelium during rat development.

1. The rat retinal pigment epithelium accumulated glutamate and taurine by saturable, temperature and Na(+)-dependent mechanisms. 2. Glutamate and taurine showed high and low affinity transport systems, with a Km of 30 microM and 80 microM, respectively. 3. The transport rates of both amino acids decreased during maturation of retinal pigment epithelial cells while their kinetic characteristics were not modified. 4. The results suggest an involvement of the retinal pigment epithelium in the regulation of glutamate and taurine levels in the neural retina and support its role as part of the blood retinal barrier.

Animals↗
PubMed2005

Retinal waves: mechanisms and function in visual system development.

A characteristic feature of developing neural networks is spontaneous periodic activity. In the developing retina, retinal ganglion cells fire bursts of action potentials that drive large increases in intracellular calcium concentration with a periodicity of minutes. These periodic bursts of action potentials propagate across the developing inner retina as waves, driving neighboring retinal ganglion cells to fire in a correlated fashion. Here we will review recent progress in elucidating the mechanisms in mammals underlying retinal wave propagation and those regulating the periodicity with which these retinal waves occur. In addition, we will review recent experiments indicating that retinal waves are critical for refining retinal projections to their primary targets in the central visual system and may be involved in driving developmental processes within the retina itself.

Animals↗
PubMed1991

A chondroitin sulfate proteoglycan may influence the direction of retinal ganglion cell outgrowth.

In the developing retina, retinal ganglion cell (RGC) axons elongate toward the optic fissure, even though no obvious directional restrictions exist. Previous studies indicate that axon-matrix interactions are important for retinal ganglion cell axon elongation, but the factors that direct elongation are unknown. Chondroitin sulfate proteoglycan (CS-PG), a component of the extracellular matrix, repels elongating dorsal root ganglion (DRG) axons in vitro and is present in vivo in the roof plate of the spinal cord, a structure that acts as a barrier to DRG axons during development. In this study, we examined whether CS-PG may regulate the pattern of retinal ganglion cell outgrowth in the developing retina. Immunocytochemical analysis showed that CS-PG was present in the innermost layers of the developing rat retina. The expression of CS-PG moved peripherally with retinal development, always remaining at the outer edge of the front of the developing axons. CS-PG was no longer detectable with immunocytochemical techniques when RGC axon elongation in the retina is complete. Results of studies in vitro showed that CS-PG, isolated from bovine nasal cartilage and chick limb, was inhibitory to elongating RGC axons and that RGC growth cones were more sensitive to CS-PG than were DRG neurites tested at the same concentrations of CS-PG. The behavior of retinal growth cones as they encounter CS-PG was characterized using time-lapse video microscopy. Filopodia of the RGC growth cones extended to and sampled the CS-PG repeatedly. With time, the growth cones turned to avoid outgrowth on the CS-PG and grew only on laminin. While numerous studies have shown the presence of positive factors within the retina that may guide developing RGC axons, this is the first demonstration of an inhibitory or repelling molecule in the retina that may regulate axon elongation. Taken together, these data suggest that the direction of RGC outgrowth in the retina may be regulated by the proper ratio of growth-promoting molecules, such as laminin, to growth-inhibiting molecules, like CS-PG, present in the correct pattern and concentrations along the retinal ganglion cell pathway.

Animals↗
PubMed2004

Effects of restricted spectral rearing on the development of zebrafish retinal physiology.

Research has shown that rearing in abnormal lighting environments affects both visual behavior and retinal physiology in zebrafish larvae. These studies, however, used only constant dark and constant white light as the experimental rearing conditions. This study assessed the effects of rearing larvae in restricted spectral lighting environments on zebrafish retinal physiology. Larvae were reared in one of seven different lighting environments: cyclic white light (control group), constant blue light, constant green light, constant orange light, cyclic blue light, cyclic green light, and cyclic orange light. Assessment of retinal physiology was done using the electroretinogram (ERG). Results showed that rearing larvae in constant light conditions caused deficits in sensitivity to ultraviolet- and short-wavelength stimuli, but had little effect on sensitivity to middle- and long-wavelength stimuli. Rearing larvae in cyclic light did not cause differences in sensitivity to middle- and long-wavelength stimuli, but did cause extreme deficits in sensitivity to ultraviolet- and short-wavelength stimuli in the cyclic green and orange light-rearing conditions. Sensitivity of the cyclic blue light-rearing group was similar to the control group to stimuli of all wavelengths. The results support the notion that the light-rearing environment impacts the development of the ultraviolet- and short-wavelength cone mechanisms but has little impact on the development of the middle- and long-wavelength cone mechanisms; these effects coincide with the development of the various cone types. This study supports the notion that the zebrafish is a viable model for studying the effects of the lighting environment on visual development.

Animals↗
PubMed1983

Modulations of neurofilament axonal transport during the development of rabbit retinal ganglion cells.

We have compared the polypeptides undergoing axonal transport in the retinal ganglion cells of neonatal and adult rabbits, and have observed the following: (1) Representative polypeptides of five different adult transport groups are axonally transported from the time of birth. (2) Polypeptides of group IV (a group that includes actin and myosin) are transported two-fold more rapidly in neonates than in adults. (3) Two polypeptides, M (145K) and L (73K) that are components of neurofilaments and move with the fifth, slowest group of transported proteins, are transported approximately eight-fold more rapidly in neonatal rabbits than in adults. (4) H, a third group V polypeptide, that serves to crosslink neurofilaments, was not detected in the rabbit optic nerve until 12 days after birth. We consider the possibility that the late induction of the crosslinker precipitates a cytoskeletal "phase transition" that may be responsible for the developmental alterations in apparent transport velocities, and may have additional consequences for neuronal development.

Aging↗
PubMed2005

Retinal angiogenesis in development and disease.

The retina has long been regarded as 'an approachable part of the brain' for investigating neurosensory processes. Cell biologists are now capitalizing on the accessibility of the retina to investigate important aspects of developmental angiogenesis, including how it relates to neuronal and glial development, morphogenesis, oxygen sensing and progenitor cells. Pathological angiogenesis also occurs in the retina and is a major feature of leading blinding diseases, particularly diabetic retinopathy. The retina and its clinical disorders have a pivotal role in angiogenesis research and provide model systems in which to investigate neurovascular relationships and angiogenic diseases.

Animals↗
PubMed2000

Retinoic acid produces rod photoreceptor selective apoptosis in developing mammalian retina.

PURPOSE: All-trans retinoic acid (ATRA) or 9-cis retinoic acid (9CRA), added to dissociated developing neural retinal cells, induces progenitor cells to adopt the rod cell's fate. Retinoic acid (RA) also produces apoptotic cell death in developing tissues. The effects of retinoids on mouse retinal development were examined. METHODS: Retinas were explanted on postnatal day (PN)1 and cultured with or without the retinal pigment epithelium (RPE) attached. Retinas were cultured for 3 weeks in the absence or presence of 100 or 500 nM ATRA or 9CRA. Morphologic development and apoptotic cell death were examined using cell-specific immunocytochemical markers, the TdT-dUTP terminal nick-end labeling (TUNEL) method, and a caspase assay. RESULTS: Retinal explants, with and without RPE, had similar age-dependent increases in opsin expression. In contrast, explants with RPE had less apoptosis during the first week than retinas without RPE. In explants with RPE, ATRA or 9CRA produced rod-selective apoptotic cell death in which 20% to 25% were lost by PN7 with no further loss by PN21. 9CRA-treated explants without RPE had a decreased number of apoptotic cells and a higher number of (rhod)opsin-positive cells at PN3. CONCLUSIONS: Factors in RPE appear to regulate rod apoptosis in developing retina. Retinoids produce rod-selective apoptotic cell death during normal rod differentiation. In contrast, retinoids accelerate the expression of opsin in retinas without RPE. These differential effects of RA on rod photoreceptors-apoptosis and differentiation-are similar to those observed in other developing tissues and play an important role in both normal and pathologic development.

Animals↗
PubMed1986

Development of anomalous retinal projections to nonvisual thalamic nuclei in Syrian hamsters: a quantitative study.

When two of the principal targets of retinofugal axons, the superior colliculus and dorsal nucleus of the lateral geniculate body, are ablated in newborn hamsters and the somatosensory (ventrobasal) or auditory (medial geniculate) thalamic nuclei are partially deafferented, the optic axons form permanent, abnormal connections in the latter nuclei. The lateral posterior nucleus of the operated hamsters also receives an anomalously large retinal projection. Here, we report on the results of a quantitative study that was undertaken in order to elucidate how these abnormal connections are formed. In normal, newborn hamsters, there is a transient retinal projection to the ventrobasal nucleus that disappears 3-4 days postnatally. Our quantitative data show that postoperatively, the volume of the retino-ventrobasal projection increases proportionately more than the volume of the ventrobasal nucleus so that the retino-ventrobasal projection in operated adult hamsters is due both to the stabilization of the normally transient projection and to a reactive sprouting that increases the size of the projection. The retino-medial geniculate projection arises de novo by reactive sprouting of optic tract fibers that normally pass over and through the nucleus; in unoperated hamsters, terminating projections are never seen at any age. The quantitative data also show that the anomalously large retino-lateral posterior projection is due almost entirely to the reactive sprouting of the normal projection and/or normal fibers of passage that are already present on the day of birth, although it is possible that a minor component can be attributed to the stabilization of a small population of normally transient retino-lateral posterior axons. The present results demonstrate that the transient retino-ventrobasal axons in normal, newborn hamsters are capable of making permanent connections with ventrobasal neurons. This finding raises the important question of the cellular mechanisms that determine whether immature neuronal connections are stabilized or eliminated. The results also suggest that during both normal and abnormal development, the choice of a target by growing axons may depend upon the axons being in proximity to a potential terminal site just at the time when that site is capable of receiving afferents.

Animals↗
PubMed2006

Retinal vascular manifestations of metabolic disorders.

Metabolic diseases have profound effects on the structure and function of the retinal circulation. The recent development of retinal photography and digital imaging has enabled more precise documentation of diabetic retinopathy, as well as other retinal microvascular changes, such as retinal arteriolar narrowing, venular dilation and isolated retinopathy signs in nondiabetic individuals. These retinal microvascular signs have been shown to be associated with long-term risks of type 2 diabetes and hypertension, components of the metabolic syndrome (e.g. obesity, dyslipidemia), and a range of macro- and micro-vascular conditions (e.g. stroke, cardiovascular mortality). There is evidence that endothelial dysfunction and inflammation might be possible mechanisms involved in the development of various retinal microvascular changes in patients with diabetes, hypertension and other metabolic disorders. Further understanding of how these processes influence the retinal vasculature might help to elucidate the diverse vascular manifestations of metabolic diseases.

Animals↗
PubMed2002

Molecular characterization and mapping of ATOH7, a human atonal homolog with a predicted role in retinal ganglion cell development.

The human ATOH7 gene encodes a basic helix-loop-helix (bHLH) transcription factor that is highly similar to Drosophila Atonal within the conserved bHLH domain. The ATOH7 coding region is contained within a single exon. We mapped ATOH7 to Chromosome (Chr) 10q21.3-22.1, a region syntenic to the segment of mouse Chr 10 where Atoh7 (formerly Math5) is located. The evolutionary relationship between ATOH7 and other atonal homologs was investigated using parsimony analysis. A direct comparison of ATH5/7 and ATH1 protein subgroups to Atonal also revealed a nonrandom distribution of amino acid changes across the bHLH domain, which may be related to their separate visual and proprioceptive sensory functions. Among bHLH genes, ATOH7 is most closely related to Atoh7. This sequence conservation extends significantly beyond the coding region. We define blocks of strong homology in flanking human and mouse genomic DNA, which are likely to include cis regulatory elements. Because targeted deletion of Atoh7 causes optic nerve agenesis in mice, we propose ATOH7 as a candidate for human optic nerve aplasia and related clinical syndromes.

Amino Acid Sequence↗
PubMed1989

Rhegmatogenous retinal detachment following cryotherapy in retinopathy of prematurity.

Three patients who had been treated with transscleral cryotherapy to the avascular retina for stage 3+ retinopathy of prematurity with threshold disease had total rhegmatogenous retinal detachments develop. In each case, the retinal detachment developed more than 1 year after treatment and resulted from a tear at the junction of the treated and untreated retina. Rhegmatogenous retinal detachment is a late complication of transscleral cryotherapy that to our knowledge has not previously been documented.

Child, Preschool↗
PubMed1988

Massive suprachoroidal hemorrhage. Follow-up and outcome of 30 cases.

The authors studied the records of 30 patients who suffered a massive suprachoroidal hemorrhage during cataract surgery. Immediate development of a retinal detachment (RD) is a very bad prognostic sign. In none of 12 such cases could the retina be reattached. Retinal complications developed in five of six patients who had vitreous incarceration and who did not have vitrectomy as opposed to only one of seven who underwent vitrectomy along with drainage of the hemorrhage. If vitreous is incarcerated in the cataract incision, drainage of the hemorrhage without vitrectomy is a dangerous procedure.

Adult↗
PubMed2000

Cytochrome oxidase activity in rat retinal ganglion cells during postnatal development.

In this study, the metabolic activity of rat retinal ganglion cells during postnatal development has been examined in vivo using cytochrome oxidase histochemistry. The intensity of staining was measured by optical densitometry. The activity of cytochrome oxidase in retinal ganglion cells progressively increased from postnatal day 0 (P0) and reached a peak during the second week of postnatal development (P10-P14) and declined thereafter. Our data show that the increased levels of cytochrome oxidase seen in developing retinal ganglion cells occur at the same time, when neuronal maturity and synaptogenesis reach their peaks.

Aging↗