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At least 73 records · Page 4Linked to original sources

Development and degeneration of retina in rds mutant mice: analysis of interphotoreceptor matrix staining in chimaeric retina.

Chimaeric mice were produced by aggregating two morulae--one of homozygous rds mutant and another from a strain of mice with normal retina, which also differed in colour genes. The interphotoreceptor matrix in the retinal sections of these chimaeras was studied histochemically. In sections, stained with colloidal iron, regions with rds/rds photoreceptor layer, characteristically lacking the outer segments, showed more intense staining of the interphotoreceptor matrix, while regions with normal receptor outer segments showed less intense staining of the matrix. In sections, stained with toluidine blue, rds/rds regions showed more intense reaction along the pigment epithelial--photoreceptor interface and less intense reaction over the inner segments in comparison to the regions with normal photoreceptors. These differential staining reactions were independent of the overlying retinal pigment epithelial cell genotype and resembled the reaction patterns in the retina of pure strain controls of the same age. Small patches, showing rds/rds type staining were also observed within areas which appeared normal. We suggest that the altered properties of the interphotoreceptor matrix in the rds retina result from gene expression within the photoreceptor cells.

Animals↗

[Studies on the ultrastructure of the inner limiting membrane of the retina--distribution of anionic sites in the inner limiting membrane of the retina].

For demonstrating ultrastructurally the distribution of anionic sites (AS) in the inner limiting membrane (ILM) of the rabbit's retina, the immersion method with cationic tracer, polyethyleneimine (PEI) was applied. This method was found to be simple and useful for the observation of AS in the ILM. In the posterior pole of the eyeball (visual streak and medullary ray), PEI particles were arranged evenly in the lamina rara (LR) of the ILM. The mean diameter of PEI particles was 20 nm, and intervals between them (40-50 nm) were the same as those of fine strands in the LR. However, the peripheral retina, the distribution of PEI particles were sparse and random, while in the lamina densa (LD) of each ILM, PEI particles were absent. AS stained with PEI were present in the residual vitreous fibers. These results may provide the morphological basis for the theory that AS of the ILM act as a charge barrier between the retina and the vitreous cavity.

Animals↗

Catecholamine receptors regulating serotonin N-acetyltransferase activity and melatonin content of chicken retina and pineal gland: D2-dopamine receptors in retina and alpha-2 adrenergic receptors in pineal gland.

The type of catecholamine receptor involved in the regulation of serotonin N-acetyltransferase (NAT) activity and melatonin (N-acetyl-5-methoxytryptamine) level in chicken retina was compared to that regulating these parameters in the pineal gland. Systemic administration of apomorphine, a dopamine receptor agonist, resulted in marked inhibition of the nocturnal increase of retinal NAT activity and melatonin content. Apomorphine did not affect NAT activity or melatonin content of the pineal gland. In contrast, clonidine, an alpha-2 adrenergic receptor agonist, inhibited the nocturnal rise in pineal NAT activity and melatonin content although being without effect on these parameters in retina. Apomorphine-induced inhibition of retinal NAT activity was blocked by spiperone, a D2-dopamine receptor antagonist, but not by antagonists of D1-dopamine, alpha-1, alpha-2 and beta adrenergic receptors. Systemic or intraocular injection of quinpirole, a D2-dopamine receptor agonist, in the middle of the dark phase of the light-dark cycle markedly reduced retinal NAT activity and melatonin level, whereas injections of SKF 38393-A, a D1-dopaminergic agonist, had no effect. The inhibitory effect of clonidine on pineal NAT activity was blocked by yohimbine, an alpha-2 adrenergic receptor antagonist. The results presented in this paper demonstrate that NAT activity and melatonin content in chicken retina and pineal gland are differentially modulated in vivo by D2-dopamine and alpha-2 adrenergic receptors, respectively. Despite the different types of receptors involved, both tissues may share a common pathway for catecholamine-mediated inhibition of melatonin biosynthesis, i.e., inhibition of adenylate cyclase activity.

Acetyltransferases↗

VEGF expression by ganglion cells in central retina before formation of the foveal depression in monkey retina: evidence of developmental hypoxia.

In macaque monkeys the foveal depression forms between fetal day (Fd) 105 and birth (Fd 172 of gestation). Before this, the incipient fovea is identified by a photoreceptor layer comprising cones almost exclusively, a multilayered ganglion cell layer (GCL), and a "domed" profile. Vessels are absent from the central retina until late in development, leading to the suggestion that the GCL in the incipient fovea may be transitorily hypoxic. Vascular endothelial growth factor (VEGF), expressed by both glial and neuronal cells and mediated by the hypoxia-inducible transcription factor (HIF)-1, is the principal factor involved in blood vessel growth in the retina. We examined VEGF expression in macaque retinas between Fd 85 and 4 months postnatal. Digoxygenin-labeled riboprobes were generated from a partial-length human cDNA polymerase chain reaction fragment, detected using fluorescence confocal microscopy, and quantified using Scion Image. High levels of VEGF mRNA were detected in astrocytes associated with developing vessels. We also detected strong expression of VEGF mRNA in the GCL at the incipient fovea prior to Fd 105, with peak labeling in the incipient fovea that declined with distance in nasal and temporal directions. By Fd 152 peak labeling was in two bands associated with development of the inner nuclear layer (INL) capillary plexus: in the inner INL where Müller and amacrine cell somas are located, and in the outer INL where horizontal cells are found. The findings suggest that at the incipient fovea the GCL is hypoxic, supporting the hypothesis that the adaptive significance of the fovea centralis is in ensuring adequate oxygen supply to neuronal elements initially located within the avascular region.

Adaptation, Physiological↗

Unique retina cell phenotypes revealed by immunological analysis of recoverin expression in rat retina cells.

Among retina-specific proteins, recoverin is unique with respect to its cellular regulation in that it is found in rods, cones, some bipolar cells, and a rare population of cells in the ganglion cell layer. Recoverin is a calcium-binding protein which inhibits rhodopsin kinase from phosphorylating rhodopsin. Because cells in the inner layers of the retina do not contain rhodopsin kinase, arrestin, or other phototransduction proteins, it seems likely that recoverin has a different function in those cell types. To study this protein more fully, antibodies were generated against the entire mouse recoverin protein, as well as against peptides from the amino and from the carboxyl termini. These antibodies confirmed the localization of recoverin in vivo and clearly demonstrated, in culture, cells which were recoverin positive and rhodopsin negative. Surprisingly, two unique cell phenotypes were seen in cell culture which are not found in vivo. These cells are [rhodopsin(+), recoverin(-)] and [arrestin(+), recoverin(-)]. These phenotypes appear to represent the same population of cells and suggest that the recoverin gene can be regulated independent of genes for other phototransduction proteins. This cell culture system will be useful for investigating environments and factors which participate in the expression of the recoverin gene, and may identify regulatory features of the recoverin gene which cause it to be illicitly expressed in small-cell lung carcinomas in cancer-associated retinopathy (CAR).

Amino Acid Sequence↗

Identification of a retina-specific footprint within the retina-specific regulatory region of the human interphotoreceptor retinoid-binding protein gene.

Regulation of the retina-specific expression of the interphotoreceptor retinoid-binding protein (IRBP) gene in transgenic mice requires sequences between nucleotide (nt) -156 and +19. DNAse I footprinting and electrophoretic mobility shift assays identified a region between nt -69 and -40 that interacts with some nuclear proteins from bovine and mouse retinas but not from a variety of other neural and non-neural tissues. The selectivity of this sequence to elicit IRBP promoter activity is indicated by their failure to bind some nuclear proteins following mutagenesis. Therefore, IRBP promoter activity is linked to nuclear protein binding at a regulatory motif between nt-69 and -40.

Animals↗

Structure and composition of the inner limiting membrane of the retina. SEM on frozen resin-cracked and enzyme-digested retinas of Macaca mulatta.

After a historical introduction describing previous observations and views on the structure and composition of the internal limiting membrane of the retina (MLI), it is concluded that no definite unifying concept exists concerning the MLI structure. The authors applied frozen resin cracking with hexamethyldisilazane (HMDS) desiccation on normal and enzyme-digested specimens of monkey retinas. Distinct differences were observed between equatorial, macular, and optic disc regions. The MLI in the equatorial and disc regions was about 70 nm thick with an outer dense, basement membranelike part and an inner, loose fibrillar meshwork fusing with the vitreous fibers. The foveal region was 400 nm thick; the dense outer layer was thicker than normal basement membrane, whereas the inner loose meshwork had only a few fibrils. The enzyme-digestion experiments showed that the fibrillar meshwork consisted mainly of collagen fibers surrounded by predominantly hyaluronic acid.

Animals↗

Ratfish retina--intracellular recordings and HRP injections in an isolated, superfused all-rod retina.

Hyperpolarizing responses to light were studied by intracellular recording in the isolated, superfused retina of the ratfish (Hydrolagus colliei). Two of these hyperpolarizing units were identified as horizontal cells by iontophoretic injection of horseradish peroxidase (HRP). These cells had rather large cell bodies (15 x 30 micrometer), elliptical dendritic arborizations measuring 150 x 300 micrometers and no axons. Since their physiological receptive fields were found to be at least 2.15 mm in diameter, it appears likely that either the photoreceptors or the horizontal cells are electrically coupled. Electron microscopy of HRP-injected horizontal cells showed their dendrites to end laterally in ribbon synapses of rods only and revealed dendro-dendritic contacts resembling gap junctions between injected and uninjected horizontal cells. The spectral sensitivity function of a dark-adapted horizontal cell can be described by a Dartnall nomogram based on a retinene pigment with lambda max = 473 nm. These findings are consistent with the histological observation that the ratfish retina appears to contain only rod photoreceptors.

Animals↗

Artificial design of three-dimensional retina-like tissue from dissociated cells of the mammalian retina by rotation-mediated cell aggregation.

The goal of this study was to establish a reliable three-dimensional culture system for the mammalian retina that allows the analysis of retinal function and dysfunction. To produce three-dimensional retinal tissues in vitro, dissociated retinal cells of neonatal rats were maintained in culture dishes on a self-made orbital shaker. On the basis of well-defined rotation conditions, dissociated free-floating cells reaggregate in the center of the culture dish to form a multicellular cluster. Subsequently, cells begin to proliferate, whereby they form spherelike retinal tissues that grow to a size of 180-210 microm. Immunohistochemical characterization of mature retinal spheres revealed the presence of ganglion cells, amacrine cells, Müller cells, and rod photoreceptors, which are arranged in different retina-like layers. Although a small number of cells undergo programmed cell death, retinal spheres remain viable for at least 35 days in culture as revealed by fluorescein diacetate and TUNEL staining. Because most biological processes involved in tissue organization such as proliferation, differentiation, apoptosis, and survival are also observable in retinal spheres, the presented novel mammalian three-dimensional culture system is not only an outstanding model for basic research but may also be of great benefit for stem cell tissue engineering and the pharmaceutical industry.

Animals↗

Localization of dystrophin isoform Dp71 to the inner limiting membrane of the retina suggests a unique functional contribution of Dp71 in the retina.

The electroretinograms (ERGs) of patients with Duchenne muscular dystrophy and an allelic variant of the mdx mouse (mdxCv3) have been shown to be abnormal. Analysis of five allelic variants of the mdx mouse with mutations in the dystrophin gene has shown that there is a correlation between the position of the mutation and the severity of the ERG abnormality. Three isoforms are expressed in the retina: Dp427, Dp260 and Dp71. Using indirect immunofluorescence and isoform-specific antibodies on retinal sections from three allelic mdx mouse strains, we have examined the localization of each of the isoforms. We show that Dp71 expression does not overlap with Dp427 and Dp260 expression at the outer plexiform layer (OPL). Instead, Dp71 is localized to the inner limiting membrane (ILM) and to retinal blood vessels. Moreover, we show that Dp260 and Dp71 differ structurally at their respective C-termini. In addition, we find that the proper localization of the beta-dystroglycan is dependent upon both Dp260 at the OPL and Dp71 expression at the ILM. Thus, Dp260 and Dp71 are non-redundant isoforms that are located at different sites within the retina yet have a common interaction with beta-dystroglycan. Our data suggest that both Dp71 and Dp260 contribute distinct but essential roles to retinal electrophysiology.

Adult↗

Dopaminergic mechanisms in the teleost retina. I. Dopamine-sensitive adenylate cyclase in homogenates of carp retina; effects of agonists, antagonists, and ergots.

A specific dopamine-sensitive adenylate cyclase has been identified in homogenates of the teleost (carp) retina. Maximal stimulation by 100 microM-dopamine resulted in a 5--10-fold increase in adenylate cyclase activity with half-maximal stimulation occurring at a concentration of 1 microM. l-Noradrenaline and l-adrenaline were some 10 times less potent than dopamine whilst the alpha- and beta-adrenoreceptor agonists, l-phenylephrine and dl-isoprenaline were inactive. Apomorphine elicited a partial stimulation of adenylate cyclase activity whilst various ergot alkaloids produced mixed agonist/antagonist responses. Dopamine-stimulated adenylate cyclase activity was potently antagonised by various neuroleptic drugs including fluphenazine, alpha-flupenthixol and alpha-piflutixol, and to a lesser extent by the butyrophenone derivatives haloperidol and spiperone. The benzamide derivatives, metoclopramide and sulpiride, together with the alpha- and beta-adrenoreceptor blocking agents, phentolamine and propranolol respectively were essentially inactive at blocking dopamine-stimulated adenylate cyclase activity. These data suggest the presence of a highly specific dopamine-sensitive adenylate cyclase in homogenates of teleost retina possessing similar pharmacological properties to the dopamine-sensitive adenylate cyclase observed in the mammalian central nervous system.

Adenylyl Cyclases↗

The protection of the retina from ischemic injury by the free radical scavenger EGb 761 and zinc in the cat retina.

We investigated the effects of a free radical scavenger (EGb 761) and zinc in experimentally induced ischemic injury in the cat retina. Total retinal ischemia for 90 min was produced in the left eyes of 40 cats by raising intraocular pressure. In group 1, 10 cats were used as control. The free radical scavenger (EGb 761, 100 mg/kg) in group 2 (10 cats) and zinc chloride (250 microg/kg) in group 3 (10 cats) were administered intravenously at the end of ischemia. In group 4, both EGb 761 (100 mg/kg) and zinc chloride (250 microg/kg) were injected into 10 cats. ERG and a histologic study were performed 1 h, 1 day, 3 days, 1 week and 2 weeks after ischemia. The amplitude of the ERG b-wave was 62.73+/-0.32, 84.31+/-6.10, 83.65+/-12.23 and 102.4+/-14.27%, and the summed amplitude of oscillatory potentials was 66.16+/-16.42, 99.44+/-14.92, 95.45+/-6.42 and 99.62+/-12.32% in each group 2 weeks after ischemia. There was no significant effect in animals that received zinc alone (group 3) by the end of 1 week but some additive effect in combining EGb 761 and zinc chloride (group 4) 1 h after ischemia. These findings suggest that the free radical scavenger EGb 761 may efficiently protect the retina from ischemic injury and zinc may have an additive effect when combined with a radical scavenger.

Animals↗

[Differentiation of the retina and pigment epithelium in the ontogeny of the common frog. 1. The retina].

Changes in the ultrastructure of the differentiating retinal cells were studied by means of electron microscopy in Rana temporaria at successive developmental stages. Common features of the onset of differentiation of the retinal cells have been shown: appearance of the granular endoplasmic reticulum elements, of the polysomes, beginning of utilization of the yolk and lipids, elimination of ovarial melanosomes. Later during the differentiation of retinal neurons the protein synthesizing machinery and Golgi complex of these cells develop markedly, the number of mitochondria increases. The differentiation of retina begins from the Müllerian cells (stage 28) which determine the direction of growth of the neuron processes. They are followed by the ganglion cells and photoreceptors (stage 29). The signs of differentiation of the inner nuclear layer neurons become apparent later, in the amacrine and horizontal cells at the same time and in the bipolars later. The main features of neuronal organization of the retina which determine the structural basis of its function of light perception are formed by stage 40.

Animals↗

Biosynthesis of protein by the retina. The properties of a cell-free system obtained from rat retina.

We describe the properties of a post-mitochondrial (30,000 g) supernatant fluid obtained from rat retina which incorporated (3H) leucine into an alkali-stable acid-insoluble fraction (protein). It contained a substance, possibly leucine, which interfered with the incorporation of (3H) leucine into acid-insoluble fractions and which could be removed by passage through Sephadex G-25 or by dialysis. Magnesium was essential for protein synthesis and potassium enhanced it. Radioactive leucine was incorporated in the protein only when both adenosine triphosphate and guanosine triphosphate were present. Puromycin inhibited protein synthesis. The amount of material required for this assay is small. The system can be used to study changes in protein synthesis in the retinas of rats with retinal dystrophies.

Adenosine Triphosphate↗

Effect of retina-derived basic and acidic fibroblast growth factor and lipoproteins on the proliferation of retina-derived capillary endothelial cells.

Retina-derived capillary endothelial (RCE) cells have been established in culture, taking advantage of their ability to proliferate at clonal density when maintained on extracellular matrix (ECM)-coated dishes in the presence of serum-supplemented medium. This cell type formed at confluence a monolayer of small, tightly packed, contact inhibited cells which expressed Factor VIII-related antigen. Both retina-derived basic and acidic fibroblast growth factors (FGF) were mitogenic when RCE cells were maintained on gelatin-coated dishes and exposed to serum-supplemented medium. Half-maximal stimulation of cell proliferation was observed with concentrations of 13 pg ml-1 for basic FGF and 2.5 ng ml-1 for acidic FGF. Maintaining RCE cells on extracellular matrix (ECM)-coated dishes greatly reduced their requirement for EGF in order to proliferate actively. Heparin strongly reduced the proliferative response of RCE cells to either basic or acidic FGF, as well as their response to serum alone, regardless of whether cells were maintained on gelatin or on ECM-coated dishes. When RCE cells maintained on ECM-coated dishes were exposed to defined medium, high density lipoproteins, transferrin, and FGF were required in order for these cells to proliferate actively.

Animals↗

Factors affecting the test-retest variability of Heidelberg retina tomograph and Heidelberg retina tomograph II measurements.

AIMS: To evaluate the test-retest variability of stereometric parameter measurements made with the Heidelberg retina tomograph (HRT) and Heidelberg retina tomograph-II (HRT-II), and to establish which parameter(s) provided the most repeatable and reliable measurements with both devices. An investigation into the factors affecting the repeatability of the measurements of this parameter(s) was conducted. METHODS: 43 ocular hypertensive and 31 glaucoma subjects were recruited to a test-retest study. One eye from each subject underwent HRT and HRT-II imaging by two observers on each of two occasions within 6 weeks of each other. Lens grading was carried out by LOCS III grading and Scheimpflug camera generated densitogram analysis. RESULTS: Rim area (RA) and mean cup depth measurements were found to be least variable. Both inter-test reference height difference and image quality had a strong relation (R(2)>0.5, p<0.0001) with inter-test RA difference and, together, are responsible for 70% of RA measurement variability. Image quality was influenced by lens opacity, cylindrical error, and age. Inter-test RA measurement differences were unrelated to the observer or visit interval. CONCLUSIONS: RA represents an appropriate measure for monitoring glaucomatous progression. Reference height difference and image quality were the factors that most influenced RA measurement variability. Image analysis strategies that address these factors may reduce test-retest variability.

Adult↗

Combined hamartoma of the retina and retinal pigment epithelium of the juxtapapillary retina and optic disc.

An 11-year-old Japanese girl had a greenish-gray, slightly elevated lesion at the optic disc and juxtapapillary retina of the right eye that was diagnosed as a combined hamartoma of the retina and retinal pigment epithelium. A gliotic epiretinal membrane partially covered the lesion. Tortuous retinal vessels, which leaked fluorescein dye, were noted ophthalmoscopically. The lesion remained stable during a follow-up period of 1 year. After reviewing the Japanese literature, we concluded that the combined hamartoma may not be as rare in Japan as previously thought.

Child↗

A genetic study of three rare retinal disorders: dystrophia retinae dysacusis syndrome, x-chromosomal retinoschisis and grouped pigments of the retina.

1) Dystrophia retinae dysacusis syndrome: Two different recessively inherited forms have been observed among 133 cases diagnosed in Finland--a country with a population of 4.6 million. 2) X-chromosomal retinoschisis: A series of 179 ophthalmoscopically verified familial cases is reported. The loci for Xg and retinoschisis are within measurable distance on the X-chromosome, but deutan dyschromatopsia is far from these. 3) Grouped pigments of the retina: No evidence of heredity was detected among 23 cases on the basis of the last four to six generations. The sex ratio is 15:8.

Adolescent↗