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At least 973 records · Page 54Linked to original sources
PubMed1996

Increased expression of specific recognition molecules by retinal ganglion cells and by optic pathway glia accompanies the successful regeneration of retinal axons in adult zebrafish.

Retinal ganglion cells (RGCs) in adult zebrafish can regenerate their axons. We show that successful axonal regeneration is accompanied by the re-expression by RGCs of mRNAs encoding specific recognition molecules that are expressed at high levels in the larval retina but are down-regulated in the adult. Message levels for 11.1 and 11.2 (two homologs of mammalian L1), n-cam (homologous to mammalian N-CAM), beta 3 (related to the beta 3 and beta 2 subunits of mammalian Na,K-ATPase), and tn-c (homologous to mammalian tenascin-C) were high in larval RGCs undergoing axonogenesis and low in adult RGCs. After an optic nerve crush, axotomized adult RGCs showed increased levels of 11.1, 11.2 and n-cam mRNA expression, whereas the levels of beta 3 and tn-cmRNA remained unchanged. The optic nerve crush also induced the expression of some of these mRNAs in the optic nerve and tract where they are not normally detectable. This lesion induced up-regulation by presumptive glia was observed for 11.1, 11.2, n-cam and beta 3 but not for tn-c. The combination of a neuronal (intrinsic) response to axotomy with an environmental (extrinsic) response may be an important determinant allowing for the successful axonal regeneration.

Animals↗
PubMed1987

Autoimmune basis for visual paraneoplastic syndrome in patients with small cell lung carcinoma. Retinal immune deposits and ablation of retinal ganglion cells.

Recently, patients with visual paraneoplastic syndrome (VPS) were described, a binocular loss of vision found in patients with small cell carcinoma of the lung (SCCL). The patients have serum antibodies against a small number of discrete antigens which are shared by the retina and small cell carcinoma cells, and which are associated with cells and processes of the ganglion cell layer of the retina. Pathologic findings are presented with regard to the presence of immunoglobulins in, and the nature of the lesions in, the central nervous system of a VPS patient. The patient's blood-brain barrier was shown to be compromised, as demonstrated by the finding of high immunoglobulin levels in the cerebrospinal fluid and immune deposits in the retina. It is further shown that within the central nervous system only the retina and optic nerve show any tissue damage with the specific loss of retinal ganglion cells and their processes. The findings support the hypothesis of an autoimmune cause for this remote effect of cancer.

Aged↗
PubMed1995

Basic fibroblast growth factor in retinal development: differential levels of bFGF expression and content in normal and retinal degeneration (rd) mutant mice.

The spatial and temporal patterns of expression and content of bFGF during postnatal development of the retina were established in C57BL/6J mice. Western blot analysis, using an anti-rodent bFGF antibody, shows multiple molecular weights of 18, 20.5, and 22 kDa of bFGF protein isolated from the adult retina. A bioassay indicates that this putative basic fibroblast growth factor (bFGF) stimulates proliferation of BALB/c 3T3 fibroblasts in a dose-dependent manner identical to an authentic bFGF standard. Immunocytochemistry reveals that bFGF immunoreactivity is located primarily in the immature photoreceptors during postnatal development and is associated with the photoreceptor outer segment/interphotoreceptor matrix complex in the adult retina. bFGF mRNA expression pattern and levels were evaluated using mouse bFGF riboprobes with in situ hybridization and quantitative ribonuclease protection assay. bFGF mRNA expression is not detectable in the retina until Postnatal Day 10 (P10), although high levels of bFGF mRNA signals were consistently observed in astrocytes in the optic disc at all postnatal ages examined. From P10 to the adult stage, bFGF mRNA was localized mainly to the photoreceptor inner segments, and the bFGF mRNA levels were approximately the same at P10 and in the adult retina. The patterns of retinal bFGF expression and content during normal development established above were compared to these parameters in the retina of rd (C57BL/6J rd/rd), a spontaneous mouse mutant in which photoreceptors degenerate shortly after birth. More bFGF immunoreactivity was detected in the outer retina during photoreceptor degeneration than was present in normal photoreceptors at equivalent ages. Densitometry measurements indicate that the level of immunoreactivity is 56% to 1.8-fold higher in rd than in the normal retina between P6 and P10, respectively. This is at least partially due to elevated bFGF mRNA expression in rd retinas during photoreceptor degeneration. In situ hybridization showed more intense bFGF mRNA hybridization signals in rd photoreceptors from P10 to P15, and RNase protection assay demonstrated much higher hybridization signals in rd retinas from P6 to P10 than in the normal retinas at these stages. More bFGF mRNA hybridization signals were also present in some cells in the inner nuclear layer following photoreceptor cell death in the rd retina but were only weakly evident in the inner nuclear layer in the normal adult retina. These results provide the first evidence that a naturally occurring neuronal degeneration is accompanied by elevated expression of bFGF in degenerating neurons prior to cell death.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1996

Non-retinal abnormalities associated with progressive retinal atrophy (PRA) in the miniature poodle.

Osmotic fragility was examined in red blood cells taken from miniature poodles with progressive retinal atrophy (PRA). In this study, the median osmotic fragility for erythrocytes (concentration of NaCl required for 50% haemolysis) was found to be significantly lower for clinically affected, compared to unaffected animals. These differences were maintained regardless of changes in erythrocyte incubation pH (7.0, 7.5). There was no difference in the slope parameter of erythrocyte osmotic fragility profiles for both sets of animals, indicating a similar variability of erythrocyte age. In groups of animals maintained with the same diet and fasted for 12 hr, and in groups of animals with no dietary constraints, total plasma cholesterol was significantly lower for affected, compared to unaffected animals. Red blood cell indices were also assessed; mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), red blood cell count (RBC) and blood haemoglobin concentration (Hb) were normal, while erythrocyte packed cell volume (PCV) was significantly reduced for affected, compared to unaffected. Data from this study suggest that the abnormal erythrocyte osmotic fragility of affected animals is unlikely to be a consequence of a higher erythrocyte surface area/volume ratio, higher plasma cholesterol concentration, or greater proportion of new to old erythrocytes, and that a general membrane defect might be associated with prcd in the miniature poodle.

Age Distribution↗
PubMed1984

Retinitis pigmentosa: a quantitative study of the apical membrane of normal and dystrophic human retinal pigment epithelial cells in tissue culture in relation to phagocytosis.

The phagocytic capabilities of both normal and dystrophic human retinal pigment epithelial cells were assessed by challenging cultures with both non-biological and biological particles. Cells from either source ingested both carbon particles and latex microspheres. Quantification of the phagocytic process in relation to microspheres showed that uptake was linear over an 8 h period and the rate was dose-dependent. All cultures phagocytosed rod outer segments from a variety of species, but excluded bacteria. By using bovine rod outer segments labelled with [H3] choline both normal and dystrophic cells were still accumulating label 24 h subsequent to challenge; however, this technique had significant problems. The introduction of any particulate matter into the culture medium resulted in changes in the apical membrane of the recipient cells. Such responses were quantified in terms of apical projections per unit area. Counts were always greater in cells challenged with biological material even if the material was not engulfed.

Aged↗
PubMed1986

Measurements of retinal microcirculation in retinal vessel occlusion before and after treatment.

Blood flow, arterial velocity, and vascular diameter were measured in patients with retinal vessel occlusion before and after treatment, especially after light coagulation. The mean values in the patient group showed significantly reduced blood flow and velocity compared to the normal group. The mean group difference before and after therapy revealed that while there is an increase in blood flow after treatment, the normal value is not reached. Individual patient values indicated both increased and decreased blood flow and velocity after treatment as compared with the values before therapy. There are various stages in microcirculatory disease and the microcirculation also behaves differently after treatment, which could be observed by measurement in vivo of the physiological flow parameters.

Adult↗
PubMed2006

The retinal fascin gene 2 (FSCN2)--partial structural analysis and polymorphism detection in dogs with progressive retinal atrophy (PRA).

The retinal fascin 2 gene (FSCN2) underwent a molecular analysis, a search for polymorphisms and an evaluation as a candidate gene for retinopathies in dogs. Specific fragments of the gene encompassing partial exon 1 and intron 1, and exons 2-5 with respective introns were sequenced and these data were deposited in the GenBank database. Three distinct polymorphic sites detectable with PCR-RFLP were found--AM050719: g.237G>A, AM050719: g.525A>G, and AM050720: g.1071A>G. No positive associations between these polymorphisms and the PRA-clinical status were observed in the investigated population consisting of Poodles, American Cocker Spaniels, and English Cocker Spaniels. In spite of that, the FSCN2 gene remains an excellent candidate gene for retinopathies in dogs and the results can contribute to further research in this field.

Animals↗
PubMed1990

Retinal accumulation of the phosducin/T beta gamma and transducin complexes in developing normal mice and in mice and dogs with inherited retinal degeneration.

Rod photoreceptors of mammalian retinas contain a 33-kDa phosphoprotein, phosducin, which complexes with the beta, gamma-subunits of transducin (T beta gamma). The level of phosducin phosphorylation is modulated by light, suggesting that the phosducin/T beta gamma complex has a pivotal role in light-regulated events that occur in photoreceptors. We have investigated, in developing mouse retinas, the age at which the complex is first detected and the subsequent accumulation of the phosducin/T beta gamma complex during postnatal life. Western blot analysis detected immunoreactivity both for phosducin and T beta in retinal homogenates of 3-day-old mice. Thereafter, the level of immunoreactivity for both proteins increased steadily, to reach adult levels in the next 2 postnatal weeks. Gel filtration analysis of extracts from immature mouse retina showed that phosducin and T beta co-eluted, like the phosducin/T beta gamma complex of adult retina, as a 77-kDa complex, indicating that the phosducin/T beta gamma complex is formed when photoreceptors first synthesize the components of the complex. While the levels of the phosducin/T beta gamma complex increased steadily during the first 2 postnatal weeks, the subunits of transducin complex, T alpha together with additional amounts of T beta gamma, only started to appear around the 7-9th postnatal day, and the level of transducin complex increased sharply at 11-14 days to reach adult levels that are similar to those of phosducin/T beta gamma complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Simulations of X and Y retinal ganglion cell behavior with a nonlinear push-pull model of spatiotemporal retinal processing.

This article describes a nonlinear model of neural processing in the vertebrate retina, comprising model photoreceptors, model push-pull bipolar cells, and model ganglion cells. Previous analyses and simulations have shown that with a choice of parameters that mimics beta cells, the model exhibits X-like linear spatial summation (null response to contrast-reversed gratings) in spite of photoreceptor nonlinearities; on the other hand, a choice of parameters that mimics alpha cells leads to Y-like frequency doubling. This article extends the previous work by showing that the model can replicate qualitatively many of the original findings on X and Y cells with a fixed choice of parameters. The results generally support the hypothesis that X and Y cells can be seen as functional variants of a single neural circuit. The model also suggests that both depolarizing and hyperpolarizing bipolar cells converge onto both ON and OFF ganglion cell types. The push-pull connectivity enables ganglion cells to remain sensitive to deviations about the mean output level of nonlinear photoreceptors. These and other properties of the push-pull model are discussed in the general context of retinal processing of spatiotemporal luminance patterns.

Adaptation, Physiological↗
PubMed1993

Abnormal distribution of retinal clusterin in retinitis pigmentosa.

Increased expression of clusterin mRNA is associated with neurodegenerative states, including retinas affected by retinitis pigmentosa (RP). We have investigated the distribution of immunoreactive clusterin in normal and RP-affected retinas. Reactivity at the inner limiting membrane, plexiform layers, and photoreceptors in normal retina accords well with clusterin's postulated role as a membrane protective agent. In RP-affected retina the organized distribution is lost and overall reactivity appears decreased. The changes in this case may reflect increased turnover or removal of clusterin, perhaps via interaction with components of the immune system.

Adult↗
PubMed2005

Retinal remodeling during retinal degeneration.

Retinal degenerations, regardless of the initiating event or gene defect, often result in a loss of photoreceptors. This formal deafferentation of the neural retina eliminates the intrinsic glutamatergic drive of the sensory retina and, perhaps more importantly, removes coordinated Ca++-coupled signaling to the neural retina. As in other central nervous system degenerations, deafferentation activates remodeling. Neuronal remodeling is the common fate of all photoreceptor degenerations.

Animals↗
PubMed2006

Retinal ganglion cell survival in development: mechanisms of retinal growth hormone action.

Several variants of growth hormone (GH) are found in the retina and vitreous of the chick embryo, where they appear to act as cell survival factors, having neuroprotective effects on retinal ganglion cells (RGCs). Here, we investigate the molecular mechanisms of the anti-apoptotic effect of GH in cultured RGCs. GH treatment increased Akt phosphorylation in these cells, which is an anti-apoptotic event. Whereas unphosphorylated Akt was detected in both nucleus and cytoplasm of RGCs by immunocytochemistry, the phosphorylated form of Akt (Akt-phos) was located primarily in the cytoplasm of both normal and apoptotic cells, although levels were markedly lower in the latter. It was found that GH treatment of RGCs reduced Akt levels, while concomitantly raising Akt-phos levels, consistent with a role for Akt signaling pathways in GH neuroprotective action. This was substantiated using Wortmannin, which, like GH antiserum, inhibited Akt phosphorylation and initiated apoptosis. The addition of Wortmannin to RGC cultures simultaneously with GH significantly reduced the anti-apoptotic effect of GH. The induction of apoptosis by GH antiserum was clearly accompanied by an increase in caspase-3 activation and PARP-1 cleavage, both of which were significantly reduced in the presence of the broad spectrum caspase inhibitor, Q-VD-OPh, which itself had a dramatic neuroprotective effect on cultured RGCs. Calpain activation appeared to be a major caspase-independent pathway to PARP-1 cleavage and apoptosis in these cells. Calpain inhibitor III (MDL 28170) was able to reduce PARP-1 cleavage and abrogate the apoptogenic effect of GH antiserum. The results support the view that caspase and calpain inhibitors are major neuroprotective agents for RGCs, and that pathways that activate both caspases and calpains are important for the anti-apoptotic actions of GH in these cells.

Amino Acid Chloromethyl Ketones↗
PubMed1996

Topographically specific effects of ELF-1 on retinal axon guidance in vitro and retinal axon mapping in vivo.

Topographic maps, which maintain the spatial order of neurons in the order of their axonal connections, are found throughout the nervous system. In the visual retinotectal projection, ELF-1, a ligand in the tectum, and its receptors in the retina show complementary gradients in expression and binding, indicating they may be positional labels for map development. Here we show that ELF-1 acts as a repellent axon guidance factor in vitro. In vivo, when the tectal ELF-1 pattern is modified by retroviral overexpression, retinal axons avoid ectopic ELF-1 patches and map to abnormally anterior positions. All these effects were seen on axons from temporal but not nasal retina, indicating that ELF-1 could determine nasal versus temporal retinotectal specificity, and providing a direct demonstration of a cell recognition molecule with topographically specific effects on neural map development.

Animals↗
PubMed2000

Autosomal dominant cone-rod retinal dystrophy (CORD6) from heterozygous mutation of GUCY2D, which encodes retinal guanylate cyclase.

OBJECTIVE: To describe the clinical features of autosomal dominant cone-rod retinal dystrophy (CRD) in a British family mapping to chromosome 17p12-p13 (CORD6), with a heterozygous mutation (Glu837Asp/ Arg838Ser) of GUCY2D. DESIGN: A prospective, clinical family survey. PATIENTS: Ten affected members of a family with autosomal dominant CRD. METHODS: Full clinical examinations were undertaken. Selected affected family members underwent electrophysiologic evaluation, scotopic static perimetry, dark adaptometry, and color vision assessment. MAIN OUTCOME MEASURES: Clinical appearance and electroretinographic responses. RESULTS: Typical clinical and electroretinographic features of childhood-onset CRD were recorded. In addition, moderate myopia and pendular nystagmus were seen in affected individuals. Color vision assessment in the youngest affected individual showed no color discrimination on a tritan axis, but retention of significant red-green discrimination. Electronegative electroretinogram responses were seen on electrophysiology in the only young family member examined. CONCLUSIONS: The phenotype associated with GUCY2D CRD is clinically distinct from that associated with other dominant CRD loci. Unusual electroretinographic responses may indicate that this mutation of GUCY2D is associated with early defects in photoreceptor synaptic transmission to second-order neurons.

Adolescent↗
PubMed1992

Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila.

Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was approximately 50 times more effective than the (-)-cis isomer in blocking the Ca2+ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca2+ channels, rather than by blocking the light-sensitive channels. Application of the Ca(2+)-channel blockers (+)-cis-diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [32P]phosphate showed much greater incorporation into eye proteins of [32P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca(2+)-channel blockers, thus, suggests that toxic increase in intracellular Ca2+ by means of voltage-gated Ca2+ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant.

Action Potentials↗
PubMed2000

A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3).

The X-linked RP3 locus codes for retinitis pigmentosa GTPase regulator (RPGR), a protein of unknown function with sequence homology to the guanine nucleotide exchange factor for Ran GTPase. We created an RPGR-deficient murine model by gene knockout. In the mutant mice, cone photoreceptors exhibit ectopic localization of cone opsins in the cell body and synapses and rod photoreceptors have a reduced level of rhodopsin. Subsequently, both cone and rod photoreceptors degenerate. RPGR was found normally localized to the connecting cilia of rod and cone photoreceptors. These data point to a role for RPGR in maintaining the polarized protein distribution across the connecting cilium by facilitating directional transport or restricting redistribution. The function of RPGR is essential for the long-term maintenance of photoreceptor viability.

Animals↗
PubMed2002

Simultaneous expression of c-Jun and p53 in retinal ganglion cells of adult rat retinal slice cultures.

PURPOSE: To determine whether the apoptosis-associated transcription factor c-Jun and the regulator protein p53 are expressed together during retinal ganglion cell (RGC) death in slice cultures of adult rat retina, and whether c-Jun expression or p53 expression is altered by glutamate. METHODS: Newborn rat RGCs were retrogradely labeled by Di-I microinjections into the superior colliculus. Retinas were isolated 2 to 4 months later, cut into 200 microm-thick slices. These slices were cultured with 0-300 microM glutamate in the presence or absence of MK801. Survival was assessed using Sytox green and ethidium homodimer. Cultures also were immunostained for Thy-1, c-Jun and/or p53. The linear density of stained RGCs was determined by confocal laser microscopy. RESULTS: RGCs in freshly-isolated adult retina slices did not express either c-Jun or p53. By 12 hours in vitro, 12.0 +/- 3.1 cells/mm of RGCs expressed c-Jun and 18.5 +/- 3.5 cells/mm of RGCs expressed p53 in control cultures. Exposure to glutamate increased both c-Jun and p53 positive RGCs in dose-dependent manner, and decreased survival in the RGC layer. Following double staining, up to 58% of cells in the RGC layer simultaneously expressed both c-Jun and p53. Time-course analysis showed that peak c-Jun expression preceded peak p53 expression in control and glutamate-treated cultures. CONCLUSIONS: The simultaneous expression of both c-Jun and p53 in the cultured adult rat slices raises the possibility that each may contribute to the mechanism of RGC death. This is supported by the increased p53 and c-Jun inductions in the presence of glutamate.

Animals↗