Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RETINA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed1984

Regulation of calmodulin- and dopamine-stimulated adenylate cyclase activities by light in bovine retina.

Neural retina from most species contains 3,4- dihydroxyphenylethylamine (dopamine) receptors coupled to stimulation of adenylate cyclase activity. It has been demonstrated that release of dopamine from its neurons and subsequent occupation of dopamine receptors is increased by light. In this study, we have shown that adenylate cyclase activity in bovine retina is highly responsive to the endogenous Ca2+-binding protein, calmodulin, and that calmodulin can increase dopamine-sensitive adenylate cyclase activity in bovine retina. We further demonstrate that both dopamine- and calmodulin-stimulated adenylate cyclase activities can be regulated by alterations in light. Bovine retinas were dissected from the eye under a low-intensity red safety light, defined as dark conditions, and incubated for 20 min in an oxygenated Krebs Henseleit buffer under either dark or light conditions. The retinas were then homogenized and adenylate cyclase activity measured in a particulate fraction washed to deplete it of endogenous Ca2+ and calmodulin. Activation of adenylate cyclase activity by calmodulin, dopamine, and the nonhydrolyzable GTP analog, guanosine-5'-(beta,gamma-imido)triphosphate ( GppNHp ), was significantly (60%) greater in particulate fractions from retinas that had been incubated under dark conditions as compared to those incubated under light conditions. Basal, Mn2+-, and GTP-stimulated adenylate cyclase activities were not altered by changes in lighting conditions. Calmodulin could increase the maximum stimulation of adenylate cyclase by dopamine in retinas incubated under either dark or light conditions, but the degree of its effect was greater in retinas incubated under light conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Dopaminergic regulation of cone retinomotor movement in isolated teleost retinas: II. Modulation by gamma-aminobutyric acid and serotonin.

In the accompanying paper we reported that 3,4-dihydroxyphenylethylamine (dopamine) induced light-adaptive retinomotor movements in teleost photoreceptors and that this effect was mediated by D2 dopamine receptors located on the photoreceptors themselves. In this study, we investigated the effects on cone retinomotor movement of three agents that have been reported by others to modulate retinal dopamine release: gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT, serotonin), and melatonin. We report here that the GABA antagonists bicuculline and picrotoxin induced light-adaptive cone contraction in dark-adapted green sunfish retinas cultured in constant darkness; thus they mimic the effect of light or exogenously applied dopamine. Since their effects were blocked by either the D2 dopamine antagonist sulpiride or by Co2+, it seems likely that these agents act by enhancing retinal dopamine release. The GABA agonist muscimol produced effects opposite to those of GABA antagonists. Muscimol inhibited light-induced cone contraction in previously dark-adapted retinas and induced dark-adaptive cone elongation in light-adapted retinas. These results suggest that in green sunfish retinas, as has been reported for other retinas, GABA inhibits dopamine release. 5-HT induced light-adaptive cone contraction in dark-adapted retinas; thus 5-HT also mimics the effect of light or exogenously applied dopamine. The effect of 5-HT was blocked by sulpiride, Co2+, or the 5-HT antagonist mianserin. These results suggest that 5-HT induces cone contraction by stimulating dopamine release. Melatonin neither inhibited dopamine-induced cone contraction in retinas cultured in the dark nor induced cone elongation in retinas cultured in the light. Our results suggest that both GABA and 5-HT (but not melatonin) affect cone retinomotor movements in green sunfish by modulating dopamine release: GABA by inhibiting and 5-HT by stimulating dopamine release. We report in the companion paper that dopamine induced contraction in isolated cone fragments. Together these observations strongly suggest that dopamine serves as the final extracellular messenger directly inducing light-adaptive cone retinomotor movement, and that GABA and 5-HT affect these movements by modulating dopamine release.

Adaptation, Physiological↗
PubMed1997

Prolonged exposure of chicks to light or darkness differentially affects the quinpirole-evoked suppression of serotonin N-acetyltransferase activity in chick retina: an impact on dopamine D4-like receptor.

Dopamine plays an important role in regulation of melatonin biosynthesis in retinas of several vertebrate species. In the avian retina, the dopamine receptor that controls melatonin production represents a D4-like subtype. Stimulation of this receptor by quinpirole (QNP) results in a dose-dependent decline of the nighttime activity of serotonin N-acetyltransferase (NAT, a key regulatory enzyme in melatonin biosynthesis) and melatonin level of the retina. The present study was undertaken to determine whether the ability of QNP to suppress nocturnal NAT activity of chick retina was affected by prolonged adaptation of animals to light and darkness. In the retina of chicks kept under a light:dark (LD) illumination cycle, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels measured at the end of the light phase were significantly higher than those found in the middle of the dark phase. In animals maintained under continuous light (LL) or darkness (DD) dopamine and DOPAC contents of the retina measured at these two time points were similar and resembled levels found during, respectively, the light and dark phase in the retina of chicks kept under LD illumination cycle. Adaptation of chicks to LL and DD resulted in an attenuated and enhanced, respectively, response of the retinal NAT activity to the suppressive action of QNP. When compared to the LD group, a parallel shift to the right (LL group) or left (DD group) of the dose-response curve for QNP was observed, and the ED50 values for this dopamine receptor agonist were 3.4-times higher (LL) or 2.8-lower (DD) than those calculated for the control LD animals. It is suggested that prolonged exposure to light or darkness, by altering the level of the retinal dopaminergic neurotransmission, may modify the reactivity of the D4-like dopamine receptors regulating NAT activity of the chick retina.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism of retinoic acid synthesis in the developing retina.

Genetic studies have shown that retinoic acid (RA) signaling is required for mouse retina development, controlled in part by an RA-generating aldehyde dehydrogenase encoded by Aldh1a2 (Raldh2) expressed transiently in the optic vesicles. We examined the function of a related gene, Aldh1a1 (Raldh1), expressed throughout development in the dorsal retina. Raldh1(-/-) mice are viable and exhibit apparently normal retinal morphology despite a complete absence of Raldh1 protein in the dorsal neural retina. RA signaling in the optic cup, detected by using a RARE-lacZ transgene, is not significantly altered in Raldh1(-/-) embryos at embryonic day 10.5, possibly due to normal expression of Aldh1a3 (Raldh3) in dorsal retinal pigment epithelium and ventral neural retina. However, at E16.5 when Raldh3 is expressed ventrally but not dorsally, Raldh1(-/-) embryos lack RARE-lacZ expression in the dorsal retina and its retinocollicular axonal projections, whereas normal RARE-lacZ expression is detected in the ventral retina and its axonal projections. Retrograde labeling of adult Raldh1(-/-) retinal ganglion cells indicated that dorsal retinal axons project to the superior colliculus, and electroretinography revealed no defect of adult visual function, suggesting that dorsal RA signaling is unnecessary for retinal ganglion cell axonal outgrowth. We observed that RA synthesis in liver of Raldh1(-/-) mice was greatly reduced, thus showing that Raldh1 indeed participates in RA synthesis in vivo. Our findings suggest that RA signaling may be necessary only during early stages of retina development and that if RA synthesis is needed in dorsal retina, it is catalyzed by multiple enzymes, including Raldh1.

Aldehyde Oxidoreductases↗
PubMed2003

Nestin positive cells in adult human retina and in epiretinal membranes.

BACKGROUND/AIM: Nestin is an intermediate filament marker for neural progenitor cells. The authors aimed to identify nestin positive cells in adult human retina and within surgically removed epiretinal membranes. METHODS: Adult human retina and epiretinal membranes were studied. Tissue was fixed and processed for semithin sections or whole mount preparations for immunohistochemical detection of nestin and glial fibrillary acidic protein (GFAP) expression. RESULTS: Nestin positive cells are most prominent at the ora serrata, possess fibrillary processes, small amounts of perinuclear cytoplasm, and are arranged radially within or superficially on the retina. In the posterior retina, speckled cytoplasmic nestin staining is seen around the nuclei of neurons. In the peripapillary retina most of the cells in the retinal ganglion cell layer are nestin positive. These cells appear to represent nestin positive neurons. Speckled cells are also seen in the myelinated portion of the optic nerve. In epiretinal membranes patches of elongated nestin positive cells were found. These cells were also positive for GFAP. CONCLUSIONS: Some neurons and glia in the adult human retina are nestin positive. Their pattern in anterior retina suggests an analogy with the ciliary marginal zone found in many other species. The role of these cells in pathological responses to retinal disease is suggested by the presence of large numbers of ectopic nestin positive cells in epiretinal membranes. The authors hypothesise that nestin positive cells represent a population of progenitor cells from normal adult human retina that differentiate to make up retinal scar tissue.

Adult↗
PubMed1996

Intraretinal oxygen distribution and choroidal regulation in the avascular retina of guinea pigs.

O2-sensitive microelectrodes were used to measure PO2 as a function of depth through the retina and choroid of anesthetized and artificially ventilated guinea pigs. The guinea pig retina is of particular interest, because it has a typically mammalian structure but no retinal circulation; it relies totally on choroidal delivery of O2 and other nutrients. Measurements of intraretinal O2 distribution in an avascular mammalian retina have not previously been reported. Under normal ventilation conditions, PO2 decreased monotonically from the choroid (33.6 +/- 2.9 mmHg, n = 11) to near zero (0.4 +/- 0.1 mmHg) at the retina-vitreous boundary. The inner half of the retina had an average PO2 of only 0.6 +/- 0.1 mmHg. Stepwise increases in inspired O2 (from 20 to 40 to 60 to 80 to 100%) had surprisingly little effect on choroidal PO2. Rapid changes (20-100%) produced overshoot-type responses in the choroid before recovery to levels only slightly above those found in normoxia. This indicates the presence of an active O2-regulatory mechanism in the guinea pig choroid. Addition of CO2 (5%) to O2 ventilation appeared to break down this control mechanism and led to dramatic and sustained increases in PO2 throughout the retina and choroid. The demonstration of an O2-regulating mechanism in the guinea pig choroid that maintains choroidal PO2 well below that in the systemic arterial blood, coupled with the observation of very low O2 levels throughout the inner retina, suggests that the O2 requirement of the inner retina in the guinea pig is small and that O2 levels in the choroid are deliberately constrained.

Animals↗
PubMed1999

A quantitative analysis of cells in the ganglion cell layer of the chick retina.

This study investigated the organization of cells in the ganglion cell layer (GCL) using Nissl staining, retrograde cell degeneration with axotomy of the optic nerve, and retrograde cell labeling by injections of horseradish peroxidase (HRP) into the optic nerve of chicks (posthatching day 1 and 8, P-1 and P-8). The total number of cells in the GCL was 6.1 x 10(6) (P-1) and 4.9 x 10(6) (P-8), and the cell density was 14,300 cells/mm2 (P-1) and 10,400 cells/ mm2 (P-8) on average. Two high-density areas, the central area (CA) and the dorsal area (DA), were observed in the central and dorsal retinas in both P-1 (22,000 cells/mm2 in CA, 19,000 cells/mm2 in DA) and P-8 chicks (19,000 cells/mm2 in CA, 12,800 cells/mm2 in DA). The cell densities in the temporal periphery (TP) and the nasal (NP) peripheral retinas were 7,800 cells/mm2 and 12,500 cells/mm2, respectively, in P-1 and 5,000 cells/ mm2 and 8,000 cells/mm2, respectively, in P-8 chicks. The cell density in the temporal periphery was 35% (P-8) lower than in the nasal periphery in both P-1 and P-8 chicks. Thirty percent (1.9 x 10(6) cells in P-1) of the total cells in the GCL were resistant to axotomy of the optic nerve. The distribution of the axotomy-resistant cells showed two high-density areas in the central and dorsal retinas, corresponding to the CA (5,800 cells/mm2) and the DA (3,200 cells/mm2). These cells also exhibited a center-peripheral increase (2,200 cells/mm2 in the TP) in P-1 chicks, but the high-density area was not found in the dorsal retina of P-8 chicks. From these data and the HRP study, the number of presumptive ganglion cells in P-8 chicks was estimated to be 4 x 10(6) (8,600 cells/mm2 on average), and the density in each area was 13,500 (CA), 10,200 (DA), and 4,300 (TP) cells/mm2. The peripheral/ center ratios of the density of ganglion cells were significantly different along the nasotemporal and dorsoventral axes. The density of ganglion cells decreased more rapidly toward the temporal periphery (TP/CA ratio: 0.47 in P-1 and 0.32 in P-8) than toward the nasal periphery (NP/CA ratio: 0.67 in P-1 and 0.52 in P-8). In contrast, there was no significant difference in the peripheral/center ratios between the dorsal retina (DP/CA ratio: 0.6 in P-1 and 0.56 in P-8) and ventral retina (VP/CA ratio: 0.58 in P-1 and 0.51 in P-8). A small peak in the density of the presumptive ganglion cells was detected in the dorsal retina of both P-1 chicks (10,800 cells/mm2) and P-8 chicks (10,200 cells/mm2). The HRP-labeled cells were small in the CA (M +/- SD: 35.7 +/- 9.1 microm2) and DA (40.0 +/- 11.3 microm2), and their sizes increased toward the periphery (63.4 +/- 29.7 microm2 in the TP) accompanied by a decrease in the cell density. However, the axotomy-resistant cells did not significantly increase in size toward the peripheral retina (12.2 +/- 2.2 microm2 in the CA, 15.2 +/- 3.2 microm2 in the DA, 15.1 +/- 3.8 microm2 in the TP). The characteristic distribution of ganglion cells could be related to visual behavior based upon the specialization of avian visual fields.

Animals↗
PubMed1998

A morphological and morphometrical study of the retina in aging SAM mice.

We investigated whether neuronal cell loss occurred as a part of normal aging of the retina in the Senescence-Accelerated Mouse, strains SAMP1 and SAMR1, and in the BALB/c mouse. All three strains showed age-related atrophy of the retina after histologically normal development. Morphometrical study revealed the following facts. The rate of loss of photoreceptor cells in the peripheral retina was greater than in the central retina in all three strains. In the central retina, the rate of loss of photoreceptor cells was greater in the SAMP1 and SAMR1 mice than in the BALB/c mice. In the peripheral retinal, the SAMR1 and SAMP1 strains had fewer cells than the BALB/c strain at all ages, but the rate of loss of these cells did not differ among the three strains. The rate of loss of ganglion cells did not differ between the peripheral and central retinas in the three strains. The SAMR1 and SAMP1 strains had fewer ganglion cells in the peripheral retina than the BALB/c strain at all ages. Because the rate of age-related loss of these cells in SAMP1 mice was not accelerated, and they were short-lived, SAMP1 mice did not show marked age-related loss. On the contrary, the SAMR1 mice showed a marked loss of photoreceptor cells and ganglion cells late in life because of their longer life span, and we propose that this strain is a suitable animal model for the study of mechanisms of age-related loss of neuronal cells in the retina.

Aging↗
PubMed2000

EST mining of the UniGene dataset to identify retina-specific genes.

Age-related macular degeneration (AMD) is a multifactorial disorder affecting the visual system with a high prevalence among the elderly population but with no effective therapy available at present. To better understand the pathogenesis of this disorder, the identification of the genetic factors and the determination of their contribution to AMD is needed. Towards this goal, we are pursuing a strategy that makes use of the EST data processed in the UniGene database and aims at the generation of a comprehensive catalogue of genes preferentially active in the human retina. Subsequently, these genes will be systematically assessed in AMD. We performed a retina EST sampling and obtained a total of 673 clusters containing only retina ESTs as well as 568 clusters with at least 30% of the ESTs in each cluster originating from retina cDNA libraries. Of these, 180 representative EST clusters with varying retina and non-retina EST contents were analyzed for their in vitro expression. This approach identified 39 transcripts with retina-specific expression. One of these genes (C18orf2) mapping to chromosome 18 was further characterized. Multiple C18orf2 transcripts display a complex pattern of differential splicing in the human retina. The various isoforms encode hypothetical polypeptides with no homologies to known proteins or protein motifs.

Alternative Splicing↗
PubMed1981

Developmental changes in the distribution of S-100 in avian neural retina.

Localization of S-100 in cells of embryonic and mature chick neural retina was studied by immunostaining of tissue sections with antiserum to S-100 and indirect immunofluorescence. Immunostaining was found to be localized predominantly in the neurons. In embryonic retina, the intensity of immunostaining increased transiently in each class of neurons at the time when they were undergoing organization within their stratum. Late embryonic and mature retina reacted weakly with the antiserum, with the exception of certain 'giant' ganglion cells that immunostained intensely. Müller cells, the only kind of glia cells in the chicken transiently in each class of neurons at the time when they were undergoing organization within their stratum. Late embryonic and mature retina reacted weakly with the antiserum, with the exception of certain 'giant' ganglion cells that immunostained intensely. Müller cells, the only kind of glia cells in the chicken transiently in each class of neurons at the time when they were undergoing organization within their stratum. Late embryonic and mature retina reacted weakly with the antiserum, with the exception of certain 'giant' ganglion cells that immunostained intensely. Müller cells, the only kind of glia cells in the chicken retina, did not react prominently with the antiserum at any of the stages examined and could not be discerned by immunostaining either in embryonic or in mature retina. The results indicate that in chick neural retina S-100 is found predominantly in neurons, and it increases and declines in different subpopulations of neurons coordinately with changes in the development and maturation if this tissue.

Animals↗
PubMed1990

Vascular and avascular retinae in mammals. A funduscopic and fluorescein angiographic study.

Intraretinal blood vessels are present in some and absent in other vertebrate species, including the mammals. Among the marsupials, both vascular and avascular retinae are seen. We determined the funduscopic appearance of the eye, investigated the functional aspects of ocular blood flow in both types of retina in marsupials and compared our results with known patterns in placental mammals. The Australian polyprotodont marsupials, the Tasmanian devil, Sarcophilus harrisii, and the quoll, Dasyurus viverrinus, together with an American polyprotodont, the Virginia opossum, Didelphis virginiana, demonstrate variable degrees of tapetal differentiation, pigmentation and a very close parallel course of their intraretinal arteries and veins over considerable distances. Using the technique of fluorescein angiography, we found that retinal blood flow in the 3 vascular Australian species commenced with arterial filling. Early venous was seen next, followed by the capillary blush. This unusual sequence of vascular flow differs from that of the arterial-capillary-venous filling seen in placental mammals. This difference is most likely a consequence of the known looped, end artery organisation found within marsupial nervous systems, of which the retinae are a part. The 2 diprotodont marsupials examined, the brushtail possum, Trichosurus vulpecula, and the sugar glider, Petaurus breviceps, possess avascular retinae. Only a small residual tuft of fluorescein-impermeable vessels projects from the optic disc into the vitreous. Interestingly, the structural complexity of the central visual system in diprotodonts all of whom possess avascular retinae) is commonly accepted as being greater than that of the stem polyprotodont line (which possess vascular retinae). If retinal function matches this internal complexity, then retinal avascularity may, as in birds, be associated with superior vision. However, as the retinae of these mammals clearly lack any nutritive mechanisms directly analogous to those in the retinae of, say, birds or the megachiropteran bats, their retinal nutritive pathways remain enigmatic.

Animals↗
PubMed2004

Requirement of neuroD for photoreceptor formation in the chick retina.

PURPOSE: The genetic control of photoreceptor cell fate in the vertebrate retina is poorly understood. Published studies suggest that the genetic program underlying photoreceptor production involves neuroD, a proneural basic helix-loop-helix (bHLH) gene. The present study investigates whether neuroD is necessary for photoreceptor cell development, by using loss-of-function analyses. METHOD: Engrailed-mediated active repression, antisense oligonucleotides, and small interfering RNA (siRNA) were used to attenuate neuroD expression and function in embryonic chick retina. The development of the retina was subsequently analyzed to determine whether these experimental manipulations would yield photoreceptor deficits in otherwise normal retina. RESULTS: Chick embryos infected with retroviruses expressing an active repression construct, En-NeuroDDeltaC, exhibited severe photoreceptor deficits. The outer nuclear layer (ONL) of the retina was no longer a contiguous structure, but became fragmented with regions that contained fewer or no photoreceptor cells. Photoreceptor deficiency was evident even before the retina became laminated, suggesting that active repression of NeuroD may have affected photoreceptor genesis. No deficiency was observed in other types of retinal cells. Culturing retinal cells in the presence of siRNA against neuroD resulted in a more than 50% reduction in the number of photoreceptor cells and an increase in the number of chx10+ cells. Subjecting the developing retina to antisense oligonucleotides against neuroD yielded fewer photoreceptor cells both in vivo and in vitro. Consistent with these observations, anti-NeuroD antibody specifically labeled the nuclei of the ONL. CONCLUSIONS: The data suggest a specific and an essential role of neuroD in photoreceptor formation in the chick retina.

Animals↗
PubMed2006

Absence of chx10 causes neural progenitors to persist in the adult retina.

PURPOSE: Mutation of the Chx10 homeobox gene in mice and humans causes congenital blindness and microphthalmia (small eyes). This study used Chx10-/- (ocular retardation) mice to investigate how lack of Chx10 affects progenitor/stem cell behavior in the retina and ciliary epithelium (CE). METHODS: The distribution of mitotic retinal progenitor cells (RPCs) during embryonic development was analyzed using phosphohistone 3 (H3)-labeling. DNA flow cytometry was used to measure DNA content. The distribution and phenotype of dividing cells in the postnatal retina and CE was analyzed by incorporation of the thymidine analogue BrdU and immunohistochemistry. RESULTS: The Chx10-/- embryonic retina maintained a constantly sized population of mitotic RPCs during development, causing the mitotic index to increase markedly over time compared with the wild type. Also, the proportion of cells in the G1 phase of the cell cycle was increased compared with the wild type. Of interest, division of RPC-like cells with neurogenic properties persisted in the adult Chx10-/- retina. Colabeling for BrdU and the neural progenitor marker nestin or the neuronal markers beta3-tubulin, syntaxin, and VC1.1 showed that new amacrine-like neurons developed in the adult central retina. By contrast, cells with these characteristics were not observed in the mature wild-type retina. In the mature CE, BrdU-positive cells were observed in both wild-type and Chx10-/- mice. However, neurogenesis from this cell population was not evident. CONCLUSIONS: Without Chx10, proliferative expansion of the embryonic RPC pool is markedly reduced. In the adult retina, lack of Chx10 results in a population of dividing neural progenitor cells that persist and produce new neurons in the central retina.

Animals↗
PubMed2006

Histone deacetylase activity regulates apaf-1 and caspase 3 expression in the developing mouse retina.

PURPOSE: Apoptosis is a form of programmed cell death essential for both tissue development and maintenance of tissue homeostasis. Apoptosis protease activating factor (Apaf)-1 and caspase 3 are downregulated in the retina during postnatal development. The decreased expression of these genes is potentially a critical survival strategy adopted to protect against accidental cell death. The purpose of this study was to investigate the transcriptional mechanism involved in the downregulation of Apaf-1 and caspase 3. METHODS: SDS-polyacrylamide gel electrophoresis and semiquantitative PCR were used to examine Apaf-1 and caspase 3 expression levels during development. TdT-mediated dUTP nick-end labeling (TUNEL) and DNA laddering were used to identify cells undergoing apoptosis. RESULTS: A decrease in expression of Apaf-1 and caspase 3 during retinal development correlated with a decreased susceptibility to an apoptotic stimulus. Furthermore, treatment with a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), resulted in widespread hyperacetylation in the retina, coinciding with transcriptional activation of Apaf-1 and caspase 3 and subsequent induction of apoptosis in postnatal day (P)5 and P15 retinas. However, inhibition of HDAC activity is not sufficient to induce apoptosis in the mature retina (P60). CONCLUSIONS: Overall, these results elicit the conclusion that downregulation of Apaf-1 and caspase 3 in the developing retina correlates with a decreased susceptibility to apoptotic stimuli and ensures the survival of the retina. Furthermore, the authors propose that, in the early postnatal retina, HDAC activity governs the transcriptional regulation of these genes. Upregulation of Apaf-1 and caspase 3 coincides with an induction of apoptosis. In the mature retina transcriptional activation of these genes or induction of apoptosis was not observed.

Acetylation↗
PubMed2006

Light-driven cone arrestin translocation in cones of postnatal guanylate cyclase-1 knockout mouse retina treated with AAV-GC1.

PURPOSE: Cone function and survival are compromised in the guanylate cyclase-1 (GC1) knockout mouse. Disruption of the light-driven translocation of cone arrestin is one of the phenotypes of cone cells in this retina: the cone arrestin in these cells is localized to the outer segments and synaptic terminals, regardless of the state of light adaptation. The purpose of this study was to determine whether the expression of GC1 restores cone arrestin translocation in the cone cells of postnatal GC1 knockout mouse retina. METHODS: Subretinal injections of AAV-GC1 were performed on 3-week-old GC1 KO mice. Electroretinographic and immunohistochemical analyses of treated retinas were carried out 5 weeks after injection. GC1 and cone arrestin antibodies were used to identify photoreceptors transduced by the AAV vector and to localize cone arrestin within cone cells, respectively. RESULTS: Treatment of GC1 knockout retinas with AAV-GC1 restored the light-driven translocation of cone arrestin in transduced cone cells. Staining patterns for cone arrestin in transduced and wild-type cone cells were indistinguishable after dark and light adaptation. In dark-adapted retinas, cone arrestin was distributed throughout the subcellular compartments of the cone cells. In light-adapted retinas, cone arrestin was concentrated in the cone outer segments. Successful restoration of cone arrestin translocation did not translate to a restoration of cone ERG responses, which remained undetectable in the treated retinas. CONCLUSIONS: AAV-mediated expression of GC1 in a subpopulation of cone cells in postnatal GC1 knockout retina restores light-driven translocation of cone arrestin in these cells. These findings, which show that fully developed cone cells that have developed in the absence of GC1 can respond to viral-mediated expression of this enzyme, support further analysis of this animal model of Leber congenital amaurosis type 1 (LCA1), a disease that results from null mutations in the gene encoding this enzyme.

Amino Acid Sequence↗
PubMed1997

Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos.

During eye development, optic vesicles evaginate laterally from the neural tube and develop into two bilayered eye cups that are composed of an outer pigment epithelium layer and an inner neural retina layer. Despite their similar embryonic origin, the pigment epithelium and neural retina differentiate into two very distinct tissues. Previous studies have demonstrated that the developmental potential of the pigmented epithelial cells is not completely restricted; until embryonic day 4.5 in chick embryos, the cells are able to switch their phenotype and differentiate into neural retina when treated with fibroblast growth factors (FGF) (Park, C. M., and Hollenberg, M. J. (1989). Dev. Biol. 134, 201-205; Pittack, C., Jones, M., and Reh, T. A. 1991). Development 113, 577-588; Guillemot, F. and Cepko, C. L. (1992). Development 114, 743-754). These studies motivated us to test whether FGF is necessary for neural retina differentiation during the initial stages of eye cup development. Optic vesicles from embryonic day 1.5 chick were cultured for 24 hours as explants in the presence of FGF or neutralizing antibodies to FGF2. The cultured optic vesicles formed eye cups that contained a lens vesicle, neural retina and pigmented epithelium, based on morphology and expression of neural and pigmented epithelium-specific antigens. Addition of FGF to the optic vesicles caused the presumptive pigmented epithelium to undergo neuronal differentiation and, as a consequence, a double retina was formed. By contrast, neutralizing antibodies to FGF2 blocked neural differentiation in the presumptive neural retina, without affecting pigmented epithelial cell differentiation. These data, along with evidence for expression of several FGF family members and their receptors in the developing eye, indicate that members of the FGF family may be required for establishing the distinction between the neural retina and pigmented epithelium in the optic vesicle.

Animals↗
PubMed2006

Diabetes alters osmotic swelling characteristics and membrane conductance of glial cells in rat retina.

The development of edema in the diabetic retina may be caused by vascular leakage and glial cell swelling. To determine whether diabetic retinopathy alters the swelling characteristics of retinal glial cells and changes the properties of the glial membrane K+ conductance, isolated retinas and glial cells of rats were investigated at 4 and 6 months of chemical diabetes. After 6 months of hyperglycemia, application of a hypotonic solution to retinal slices induced swelling of glial cell bodies, a response not observed in control retinas. The osmotic glial cell swelling was blocked by inhibitors of phospholipase A2 or cyclooxygenase and by a thiol-reducing agent. Glial cells from diabetic retinas displayed a decrease of K+ currents that was associated with an altered subcellular distribution of the K+ conductance and a loss of perivascular Kir4.1 protein. The observation that swelling of cells in control retinas was inducible with K+ channel-blocking Ba2+ ions suggests a relationship between decreased K+ inward currents and osmotic cell swelling in diabetic retinas. The data show that glial cells in diabetic retinas are more sensitive to osmotic stress, which is associated with a decrease of K+ currents, than cells in control retinas. It is suggested that these alterations may be implicated in the development of diabetic retinal edema.

Animals↗
PubMed1984

alpha-Tocopherol in the developing rat retina: a high pressure liquid chromatographic analysis.

High pressure liquid chromatography was used to measure alpha-tocopherol in the retinas of rats reared in a cyclic light or dark environment. These measurements were performed on extracts of whole retinas during the developmental period, 18-60 days, and on isolated ROS from adult animals. Similar alpha-tocopherol determinations were performed on retinas and isolated ROS following exposure of rats to intense visible light for 24 hr periods. The results show that alpha-tocopherol is chromatographically separated from the vitamin A derivatives found in the retina and is pure, as judged by mass spectrometry. In the retinas of cyclic light and dark reared rats, alpha-tocopherol accumulates in an age dependent fashion, so that at 60 days the level is nearly double that of animals at 18-20 days of age (P less than 0.001). Because the age dependent accumulation of rhodopsin is greater in dark reared rats, the average molar ratio of rhodopsin to alpha- tocopherol in the retina of dark reared animals is 25% higher than in cyclic light rats. Following exposure of rats to intense visible light for 24 hr periods, alpha-tocopherol concentrations in the retina were unchanged from the levels in control animals. In adult animals the concentration of alpha-tocopherol in ROS is 2.5-3.5 times higher than in whole retina. ROS from adult cyclic light reared rats also contain an average of 43% more alpha-tocopherol per mg protein than ROS from dark maintained animals (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗