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At least 739 records · Page 41Linked to original sources
PubMed2001

Semaphorin 3A elicits stage-dependent collapse, turning, and branching in Xenopus retinal growth cones.

The semaphorin receptor, neuropilin-1 (NP-1), was first identified in Xenopus as the A5 antigen and is expressed abundantly in developing retinal ganglion cells (RGCs). Here we show that growth cones acquire responsiveness to semaphorin 3A (Sema 3A) with age and that the onset of responsiveness correlates with the appearance of NP-1 immunoreactivity. Growth cones from "old" (stage 35/36) retinal explants collapse rapidly (5-10 min) in response to Sema 3A and turn away from a gradient of Sema 3A, whereas "young" growth cones (stage 24) are insensitive to Sema 3A. Moreover, transfection of full-length NP-1 into young neurons confers premature Sema 3A sensitivity. When young neurons are aged in culture they develop Sema 3A sensitivity in parallel with those in vivo, suggesting that an intrinsic mechanism of NP-1 regulation mediates this age-dependent change. Sema 3A-induced collapse is transient, and after recovery approximately 30% of growth cones extend new branches within 1 hr, implicating Sema 3A as a branching factor. Pharmacological inhibitors were used to investigate whether these three Sema 3A-induced behaviors (collapse, turning, and branching) use distinct second messenger signaling pathways. All three behaviors were found to be mediated via cGMP. In situ hybridization shows that Sema 3A is expressed in the tectum and at the anterior boundary of the optic tract where axons bend caudally, suggesting that Sema 3A/NP-1 interactions play a role in guiding axons in the optic tract and in stimulating terminal branching in the tectum.

Aging↗
PubMed2000

Two homeobox genes define the domain of EphA3 expression in the developing chick retina.

Graded expression of the Eph receptor EphA3 in the retina and its two ligands, ephrin A2 and ephrin A5 in the optic tectum, the primary target of retinal axons, have been implicated in the formation of the retinotectal projection map. Two homeobox containing genes, SOHo1 and GH6, are expressed in a nasal-high, temporal-low pattern during early retinal development, and thus in opposing gradients to EphA3. Retroviral misexpression of SOHo1 or GH6 completely and specifically repressed EphA3 expression in the neural retina, but not in other parts of the central nervous system, such as the optic tectum. Under these conditions, some temporal ganglion cell axons overshot their expected termination zones in the rostral optic tectum, terminating aberrantly at more posterior locations. However, the majority of ganglion cell axons mapped to the appropriate rostrocaudal locations, although they formed somewhat more diffuse termination zones. These findings indicate that other mechanisms, in addition to differential EphA3 expression in the neural retina, are required for retinal ganglion axons to map to the appropriate rostrocaudal locations in the optic tectum. They further suggest that the control of topographic specificity along the retinal nasal-temporal axis is split into several independent pathways already at a very early time in development.

Animals↗
PubMed2000

Activin A promotes progenitor differentiation into photoreceptors in rodent retina.

Activins are TGF beta-like proteins that were first discovered for their actions on the reproductive system, but have subsequently been shown to play a role in a variety of developmental processes. Previous studies have demonstrated that activins and their receptors are present in the developing retina, as well as other regions of the embryonic nervous system. We used both in vitro and in vivo approaches to test for functions of activin during retinal development. We found that activin A treatment of embryonic day 18 rat retinal cultures causes the progenitor cells in the cultures to exit the cell cycle and differentiate into rod photoreceptors. This effect is dose-dependent and the promotion of rod photoreceptor differentiation is specific, since the other primary retinal neurons generated in these cultures, the C1+ amacrine cells, are not affected by activin A treatment. Mice with homozygous deletion of the activin betaA gene show a specific decrease in the number of rod photoreceptors compared to wild-type or heterozygous littermates. These data demonstrate that activin A is an important regulator of photoreceptor differentiation in the developing retina.

Activins↗
PubMed1994

Involvement of c-Jun in the control of glucocorticoid receptor transcriptional activity during development of chicken retinal tissue.

The ability of the glucocorticoid receptor (GR) to induce gene expression in embryonic chicken retinal tissue increases dramatically during development, although the quantity of the receptor molecules does not change greatly with age. This study examines the possible involvement of c-Jun in the developmental control of GR activity. Expression of c-Jun in retinal tissue was high at early embryonic ages and declined during development. Elevation of c-Jun expression in retina of mid-developmental ages by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or by introduction of a c-Jun expression vector, caused a pronounced decline in the inducibility of the endogenous glutamine synthetase gene and the transiently transfected CAT constructs p delta G46TCO and pGS2.1CAT, that are controlled by a minimal consensus glucocorticoid response element (GRE) promoter and the glutamine synthetase promoter, respectively. The effect of c-Jun was dose dependent and could be reversed by overexpression of GR. C-Jun-evoked repression of GR activity could be relieved by overexpression of Jun D. Overexpression of Jun D could also elevate the responsiveness of early embryonic retina to glucocorticoids and cause a 5-fold increase in p delta G46TCO induction. The effect of Jun D could be reversed by overexpression of c-Jun. Expression of c-Jun might therefore be important for repression of GR activity at early embryonic ages.

Animals↗
PubMed1984

Retinal detachment following the acute retinal necrosis syndrome.

Twenty-six patients with the acute retinal necrosis involving 32 eyes have been followed at the Bascom Palmer Eye Institute. Sixteen eyes developed retinal detachment and surgical repair was attempted in thirteen. Ten eyes were successfully reattached. Vitreous surgery was necessary in ten eyes and was performed in eight of the ten successful eyes. The clinical characteristics of the retinal detachments as well as the surgical procedures and results are presented.

Acute Disease↗
PubMed2001

Differentiation and migration of astrocyte precursor cells and astrocytes in human fetal retina: relevance to optic nerve coloboma.

The presence of astrocyte precursor cells (APCs) and time course and topography of astrocyte differentiation during development were investigated by triple-label immunohistochemistry with intact fetal and adult human retinas. Throughout retinal development and adulthood, expression of Pax2 was restricted to cells of the astrocytic lineage. Three distinct stages of astrocytic differentiation were identified during development: i) Pax2+/vimentin+/GFAP- APCs; ii) Pax2+/vimentin+/GFAP+ immature perinatal astrocytes; and iii) Pax2+/vimentin-/GFAP+ mature perinatal astrocytes. In adult, cells with the antigenic phenotype of mature perinatal astrocytes were restricted to a region surrounding the optic nerve head (ONH), whereas cells at a fourth stage of differentiation, adult astrocytes (Pax2-/vimentin-/GFAP+), were apparent throughout the vascularized retina. APC appearance was centered around the ONH and preceded the appearance of perinatal astrocytes. A cluster of Pax2+ somas was also present in a small region surrounding the ONH at the ventricular surface of the developing retina, which suggests the existence of two distinct sites of astrocytic differentiation. The coincidence in the location of APCs and perinatal astrocytes at the ventricular zone with that of optic nerve colobomas, together with the association of Pax2 gene mutations with this condition, suggests that coloboma formation may result from impaired astrocyte differentiation during development.

Adult↗
PubMedDate not supplied

Atypical retinitis proliferans, retinal telangiectasis, and vitreous hemorrhage in a patient with tuberous sclerosis.

This report describes an unusual case of recurrent vitreous hemorrhage and atypical retinal neovascularization in a patient with tuberous sclerosis. During three years of observation, the patient also developed retinal telangiectasis with macular edema and lipid exudation. Although the patient did not have an obvious astrocytic hamartoma, a diffuse, flat retinal hamartoma within the nerve fiber layer was suspected.

Adult↗
PubMed1992

Biodegradable microspheres containing adriamycin in the treatment of proliferative vitreoretinopathy.

The use of biodegradable polymer microspheres containing adriamycin for the treatment of proliferative vitreoretinopathy (PVR) in an experimental rabbit model was investigated. A single injection of microspheres containing 10 micrograms of adriamycin effectively decreased traction retinal detachment to 10% (n = 10), whereas 50% of eyes injected with blank microspheres (n = 10) developed retinal detachment (P < 0.05). A single injection of microspheres, containing 3 micrograms of adriamycin, did not suppress retinal detachment. Electroretinographic and histologic studies confirmed that the 10 micrograms injection of adriamycin in microspheres was not toxic to the retina, although the injection of the same amount of free adriamycin caused retinal necrosis and detachment. Thus, microspheres containing adriamycin hold promise as a new treatment modality for PVR.

Animals↗
PubMed1989

Development of the retinal tapetum lucidum of the walleye (Stizostedion vitreum vitreum).

The development of the retinal tapetum lucidum within the cells of the retinal pigment epithelium (RPE) has been investigated by both light and electron microscopy in the walleye (Stizostedion vitreum vitreum) in specimens ranging in total length from 25-140 mm. In addition changes in the arrangement of the photoreceptors (both rods and cones) in both light and dark-adaptation have also been studied. At 25 mm no evidence of a tapetum is present. At about 30 mm it makes its initial appearance as granular bodies formed within the apical smooth endoplasmic reticulum (SER) cisternae of the RPE cells in the superior temporal fundus. The developing tapetum then spreads peripherally and continues to thicken in existing areas. By 90 mm it is well established throughout the fundus but always appears better developed in the superior fundus. By 125-140 mm it is essentially adult in appearance. At 60-70 mm the rods and cones begin to form bundles producing macroreceptors of 20-30 photoreceptors. In dark-adaptation the rod bundles are retracted and have one or more cone cells centrally located in each bundle, with the bundles separated from one another by melanosomes. Initially when no tapetal material is present, post-larval walleye are positively phototactic and feed on zooplankton. In the adult condition when a tapetum lucidum and large macroreceptors are present, the walleye is negatively phototactic and feeds almost exclusively on larger organisms such as other fish.

Adaptation, Ocular↗
PubMed2000

Nitric oxide synthase activity in retinas from non-insulin-dependent diabetic Goto-Kakizaki rats: correlation with blood-retinal barrier permeability.

The aim of this work was to examine whether the non-insulin-dependent diabetic Goto-Kakizaki (GK) rats develop retinal changes with similar characteristics to those observed in insulin-dependent diabetic rats in what concerns blood-retinal barrier (BRB) permeability, nitric oxide (NO) production, and retinal IL-1beta level. BRB permeability was evaluated by vitreous fluorophotometry. NO synthase (NOS) activity was assessed by the production of l-[(3)H]-citrulline and retinal IL-1beta level was determined by ELISA. The expression of the inducible isoform of NOS (iNOS) protein was evaluated by Western blot analysis and immunohistochemistry. The in vivo studies indicated that in GK rats the BRB permeability to fluorescein was increased (787.81 +/- 68 min(-1)) in comparison to that in normal Wistar rats (646.6 +/- 55 min(-1)). The ex vivo studies showed that in retinas from GK rats the NOS activity was higher (207 +/- 28.9 pmol l-[(3)H]-citrulline/mg protein/30 min) than that in normal Wistar rats (125 +/- 32.3 pmol l-[(3)H]-citrulline/mg protein/30 min). These results were correlated with an increase in the protein level of iNOS in the retinas of GK rats, which was confirmed not only by the study of the iNOS protein expression but also by the use of NOS activity inhibitors. Indeed, the data about the effect of specific inhibitors on the NOS activity revealed that in retinas from GK rats the most effective inhibitor was aminoguanidine, which predominantly inhibits the iNOS isoform whereas in retinas from normal Wistar rats it was N(G) nitro l-arginine that predominantly inhibits the constitutive isoforms of NOS. In summary, in retinas from GK rats there is an increased production of NO which may contribute to the BRB breakdown.

Animals↗
PubMed2004

Expression of melanopsin during development of the rat retina.

There is accumulating evidence that the new opsin-like protein, melanopsin, in adult rodents functions as non-visual photoreceptor. Here we report using immunohistochemistry and in situ hybridisation that melanopsin during rat retinal development is expressed already at prenatal day 18 in cells of the inner neuroblast layer. Perinatally the melanopsin positive cells increase in number and migrate towards the ganglion cell layer. During early postnatal development a melanopsin immunoreactive dendritic network is formed in the inner plexiform layer. Melanopsin is exclusively expressed in PACAP-containing cells which in adults become the retinal ganglion cells constituting the retinohypothalamic tract. The early expression of melanopsin argues for a photoreceptor role in the developing retinohypothalamic tract which is functional as early as the first day after birth.

Animals↗
PubMed1992

Further study of the aberrant optic nerve projection to olfactory cortex.

When implanted into the cerebral hemisphere, the regenerating optic nerve of the adult frog (Rana pipiens) forms a well-defined terminal field in the pars ventralis of the lateral (olfactory) cortex, and sometimes expands medially into the postolfactory eminence. These adjacent areas receive their normal input from the main olfactory bulb. The aberrant projection extends caudally toward the core neuropil of the medial amygdaloid nucleus, which receives its normal input from the accessory olfactory bulb, but does not enter this vomeronasal sector of the amygdala. The present study tests whether: 1) optic fibers would innervate the vomeronasal amygdala after surgical ablation of the accessory olfactory bulb, 2) the projection would transpose into adjacent cortex after olfactory cortex lesions, and 3) the projection would overflow into adjacent areas after being amplified by hemisection at the di-telencephalic junction (to minimize escape of fibers into the diencephalon). The retinal projection always terminated in the olfactory cortex when this area was intact, or in spared fragments of it after radical cortical lesions, but never entered the vomeronasal amygdala in any specimen, as studied by autoradiographic and horseradish peroxidase tracing techniques. With forebrain hemisection, the cortical terminal field increased in thickness but remained confined to the olfactory area. However, the interruption of the lateral forebrain bundle induced a new projection to the striatum in a region neighboring but separate from the olfactory cortical field. These findings support the hypothesis that retinal fibers have a specific affinity for primary olfactory cortex that is not normally allowed expression in development. Retinal fibers may also have a latent affinity for the striatum that is unmasked after deafferentation.

Animals↗
PubMed2006

Evidence for Notch signaling involvement in retinal regeneration of adult newt.

Involvement of Notch signaling in retinal regeneration by transdifferentiation of pigment epithelium cells was investigated using the adult newt Cynops pyrrhogaster. During retinal regeneration, cells expressing Notch-1 first appeared in the regenerating retina one to two cells thick (stage E-3) originated from the retinal pigment epithelium (RPE) cells, and increased in number as the regenerating retina increased in thickness. Notch-1 expression was decreased in the central retina in association with cell differentiation and became restricted to the peripheral retina. Administration of a Notch signaling blocker DAPT resulted in the appearance of a cluster of neurons, earlier than in normal regeneration, along the regenerating retina 1-3 cells thick (stage E-3 to I-1). Immunoblot analysis suggested that DAPT could perturb the processing of Notch-1. Similar results were obtained in the newt embryonic retinal development. These results suggest that the Notch-1 signaling system may be reset to regulate neurogenesis during retinal regeneration. However, PCR analysis revealed that the adult newt RPE cells express Hes-1, neurogenin1 and sometimes Delta-1 Hes-1, neurogenin1 and sometimes Delta-1 all of which are differently regulated in association with retinal regeneration, implying that Notch signaling might also be involved early in the process of transdifferentiation.

Animals↗
PubMed2000

Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx.

BACKGROUND: Terminal differentiation of many cell types is controlled and maintained by tissue- or cell-specific transcription factors. Little is known, however, of the transcriptional networks controlled by such factors and how they regulate differentiation. The paired-type homeobox transcription factor, Crx, has a pivotal role in the terminal differentiation of vertebrate photoreceptors. Mutations in the human CRX gene result in either congenital blindness or photoreceptor degeneration and targeted mutation of the mouse Crx results in failure of development of the light-detecting outer segment of photoreceptors. RESULTS: We have characterized the transcriptional network controlled by Crx by microarray analysis of gene expression in developing retinal tissue from Crx(+/+) and Crx(-/-) mice. These data were combined with analyses of gene expression in developing and adult retina, as well as adult brain. The most abundant elements of this network are ten photoreceptor-specific or -enriched genes, including six phototransduction genes. All of the available 5' regulatory regions of the putative Crx targets contain a novel motif that is composed of a head-to-tail arrangement of two Crx-binding-element-like sequences. Analysis of the 5' regions of a set of mouse and human genes suggests that this motif is specific to Crx targets. CONCLUSIONS: This study demonstrates that cDNA microarrays can be successfully used to define the transcriptional networks controlled by transcription factors in vertebrate tissue in vivo.

Animals↗
PubMed1999

Orbital color Doppler imaging of optic nerve tumors.

OBJECTIVE: To report changes in retinal arterial and venous blood flow pattern in two patients with tumors involving the entire optic nerve. METHODS: Retrospective review of one patient with clinical and neuroimaging characteristics typical of bilateral optic nerve gliomas and one patient with a probable meningioma of the left optic nerve sheath. RESULTS: The optic nerve glioma patient had reduced peak systolic velocity of central retinal arteries bilaterally, while the patient with an optic nerve sheath meningioma had relatively low central retinal artery flow velocity and intermittent blood flow in the central retinal vein on the affected side. CONCLUSIONS: Reduced retinal arterial flow velocities in the setting of optic nerve gliomas may correlate with the presence of optic nerve disease. Phasic blood flow in the central retinal vein with optic nerve sheath meningioma may be the reason that some patients with this tumor develop retinal choroidal venous anastomoses.

Aged↗
PubMed2003

Loss of the perforin cytotoxic pathway predisposes mice to experimental cytomegalovirus retinitis.

AIDS-related human cytomegalovirus (HCMV) retinitis continues to be a chronic ophthalmologic problem among human immunodeficiency virus type 1 (HIV-1)-infected patients who do not respond to highly active antiretroviral therapy. Although HCMV retinitis occurs during HIV-1-induced immunosuppression, the precise effector mechanism(s) that fails during the immunopathogenesis of AIDS to allow onset and progression of HCMV retinal disease remains unclear. We therefore performed a series of experiments to explore the relative roles of distinct pathways of lymphocyte-mediated cytotoxicity in either resistance or susceptibility to experimental murine cytomegalovirus (MCMV) retinitis in mice. Whereas mutant C57BL/6 mice deficient in the Fas/FasL cytotoxic pathway (gld mice) were identical to normal C57BL/6 mice and exhibited absolute resistance to retinal necrosis following subretinal MCMV inoculation, knockout C57BL/6 mice deficient in the perforin cytotoxic pathway (PKO mice) were susceptible to MCMV retinitis. Susceptibility of PKO mice to MCMV retinitis correlated with increased ocular MCMV titers when compared with ocular MCMV titers of gld and normal mice. Since mice with retrovirus-induced immunodeficiency syndrome (MAIDS) exhibited a frequency and severity of MCMV retinitis that were equivalent to those observed in PKO mice, we hypothesized that susceptibility to MCMV retinitis during MAIDS correlates with a decrease in the perforin cytotoxic pathway. To test this hypothesis, we developed a quantitative competitive reverse transcription-PCR assay to measure mouse perforin mRNA levels in the splenic T lymphocytes and MCMV-inoculated eyes of normal mice or mice with MAIDS. Perforin mRNA levels in splenic T lymphocytes were significantly decreased during MAIDS, by approximately 100-fold, from perforin mRNA levels in normal mice. Moreover, MCMV-inoculated eyes destined to develop retinitis during MAIDS also showed a significant decrease in perforin mRNA levels from the perforin mRNA levels of MCMV-inoculated eyes of normal mice destined to be resistant to retinitis. As expected, perforin mRNA could not be detected in unmanipulated and uninfected eyes of normal mice. These results provide the first evidence that the perforin cytotoxic pathway is more important than the Fas/FasL cytotoxic pathway in providing resistance to experimental MCMV retinitis and that loss of the perforin cytotoxic pathway predisposes to MCMV retinitis.

Animals↗
PubMed1999

Phakic anterior chamber lenses for the correction of myopia: a 7-year cumulative analysis of complications in 263 cases.

OBJECTIVE: To perform a prospective, clinical trial to determine the potential cumulative complications of patients implanted with angle-supported phakic intraocular lenses (PIOLs) for the correction of myopia. DESIGN: Nonrandomized, prospective, comparative trial. PARTICIPANTS: Two hundred sixty-three eyes of 160 consecutive patients were included. INTERVENTION: Angle-supported anterior chamber intraocular lenses were implanted into phakic eyes. MAIN OUTCOME MEASURES: Night halos and glare were recorded. Central endothelial cell count, postoperative inflammation, applanation tonometry, cataract development, retinal detachment, and pupil ovalization were recorded by the same physician. RESULTS: Night halos and glare were reported as significant by 20.2% at 1 year and 10% at year 7 of follow-up. This complication was significantly lower in the larger optical zone PIOL (ZSAL-4) than in the ZB5M/ZB5MF group (P < 0.05). Acute postoperative iritis was observed in 4.56% of cases. High intraocular pressure that required antiglaucoma medications appeared in 7.2% of cases. Central corneal endothelial cell density was significantly decreased at postoperative month 3 (P < 0.0001). The percentages of cell loss were 3.76% at month 3 and 1.83% at year 1, and then the percentages decreased by 1.37% more at year 2, 0.72% at year 3, 0.3% at year 4, 0.6% at year 5, 0.4% at year 6, and 0.56% at year 7. The total cumulative loss of central endothelial cells after 7 years was 8.37%. Pupil ovalization was present in 5.9% of cases, although smaller degrees of this complication were observed in another 10.3%. Retinal detachment appeared in 3% of cases. The PIOL explantation was decided in 11 cases (4.18%) because of cataract development (9 cases) and extreme pupil ovalization associated with severe glare (2 cases). The Kaplan-Meier cumulative survival analysis study showed an expected period free from complication of 86.5% for IOP elevation, 98.75% for endothelial cell count inferior to 1500 cells/mm2, 86.97% for pupil ovalization, 95.43% for retinal detachment, and 89.02% for explantation. CONCLUSIONS: Angle-supported PIOL appeared to be well tolerated by the corneal endothelium with a low rate of other complications. Pupil ovalization seemed to be a specific problem for this type of PIOL.

Adult↗
PubMed2002

Inhibition of nitric oxide synthase induces increased production of growth-associated protein 43 in the developing retina of the postnatal rat.

We investigated the effects of N(G)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, on retinal development in the postnatal rat by immunocytochemistry and immunoblotting using antisera against neuronal nitric oxide synthase (nNOS) or growth-associated protein 43 (GAP-43). An nNOS-immunoreactive band of 155 kDa and a GAP-43-immunoreactive band of 48 kDa were present in the extracts of both control and L-NAME-treated rat retinas. The intensity of the nNOS-immunoreactive band was much weaker in the treated rats, whereas the intensity of the GAP-43-immunoreactive band of 48 kDa was much stronger in the treated rats. Much stronger GAP-43 immunoreactivity was visible in the inner plexiform layer (IPL) of the treated retinas at P10, P14 and P21. Our findings suggest that NO may play an important role in the maturation of the IPL in the developing rat retina.

Aging↗