Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “retinal development”

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 883 records · Page 49Linked to original sources
PubMed1997

Functional development of intrinsic properties in ganglion cells of the mammalian retina.

Senosory neurons manifest pronounced changes in excitability during maturation, but the factors contributing to this ubiquitous developmental phenomenon are not well understood. To assess the contribution of intrinsic membrane properties to such changes in excitability, in the present study whole cell patch-clamp recordings were made from developing ganglion cells in the intact retina of postnatal rats. During a relatively brief developmental period (postnatal days P7-P27) ganglion cells exhibited pronounced changes in the discharge patterns generated by depolarizing current injections. The youngest cells (P7-P17) typically responded to maintained depolarizations with only a single spike or a rapidly adapting discharge pattern. In contrast, the predominant response mode of more mature cells (P21-P27) was a series of repetitive discharges that lasted for the duration of the depolarization period, and by P25 all cells responded in this manner. These functional changes characterized all three morphologically defined cell classes identified by intracellular labeling with Lucifer yellow. To determine if expression of the potassium current (Ia) and the kinetics of the Na-channel related to the increased excitability of developing ganglion cells described above, current- and voltage-clamp recordings were made from individual neurons. The different firing patterns manifested by developing retinal ganglion cells did not reflect the presence or absence of the Ia conductance, although cells expressing Ia tended to generate spikes of shorter duration. With maturation the speed of recovery from inactivation of the Na current increased markedly and this related to the increased excitability of developing ganglion cells. Neurons yielding only a single spike to maintained depolarization were characterized by the slowest speed of recovery; cells with rapidly adapting discharges showed a faster recovery and those capable of repetitive firing recovered fastest from Na-channel inactivation. It is suggested that these changes in intrinsic membrane properties may relate to the different functional roles subserved by ganglion cells during development.

Action Potentials↗
PubMed1998

Widespread integration and survival of adult-derived neural progenitor cells in the developing optic retina.

Adult rat hippocampus-derived neural progenitor cells (AHPC) show considerable adaptability following grafting to several brain regions. To evaluate the plasticity of AHPCs within the optic retina, retrovirally engineered AHPCs were grafted into the vitreous cavity of the adult and newborn rat eye. Within the adult eye, AHPCs formed a uniform nondisruptive lamina in intimate contact with the inner limiting membrane. Within 4 weeks of grafting to the developing eye, the AHPCs were well integrated into the retina and adopted the morphologies and positions of Müller, amacrine, bipolar, horizontal, photoreceptor, and astroglial cells. Although the cells expressed neuronal or glial markers, none acquired end-stage markers unique to retinal neurons. This suggests that the adult-derived stem cells can adapt to a wide variety of heterologous environments and express some but not all features of retinal cells when exposed to the cues present late in retinal development.

Age Factors↗
PubMed1985

Retinal pigment epithelial detachments in the elderly: classification and outcome.

Sixty-four eyes of 57 elderly patients with pigment epithelial detachments (PEDs) were studied with the aim of describing their morphological features and identifying prognostic factors. They were classified into four groups according to the following characteristics: early fluorescence, late fluorescence, shallow detachment with limited fluorescence ('drusen type'), irregular fluorescence. The following conclusions were drawn: 30% developed demonstrable subretinal new vessels; all groups except the drusen type were susceptible, the irregular group being particularly prone. 10% developed retinal pigment epithelial tears, and these occurred almost exclusively in the slow fluorescent group. Flattening of PEDs was a feature of drusen type and early fluorescent groups. Most patients lost vision. RPE tears occurred within a few months of presentation with immediate loss of vision; likewise rapid loss of vision followed the development of demonstrable new vessels, though not necessarily in those with changes thought to imply the presence of new vessels. Flattening after prolonged detachment was associated with pigment epithelial atrophy and invariable loss of vision. Visual acuity was maintained consistently only in those eyes with persistent detachment.

Aged↗
PubMed2005

Xenopus aristaless-related homeobox (xARX) gene product functions as both a transcriptional activator and repressor in forebrain development.

Mutations in the aristaless-related homeobox (ARX) gene have been found in patients with a variety of X-linked mental retardation syndromes with forebrain abnormalities, including lissencephaly. Arx is expressed in the developing mouse, Xenopus, and zebrafish forebrain. We have used whole-mount in situ hybridization, overexpression, and loss-of-function studies to investigate the involvement of xArx in Xenopus brain development. We verified that xArx is expressed in the prospective diencephalon, as the forebrain is patterned and specified during neural plate stages. Expression spreads into the ventral and medial telencephalon as development proceeds through neural tube and tadpole stages. Overexpression of xArx resulted in morphological abnormalities in forebrain development, including loss of rostral midline structures, syn- or anophthalmia, dorsal displacement of the nasal organ, and ventral neural tube hyperplasia. Additionally, there is a delay in expression of many molecular markers of brain and retinal development. However, expression of some markers, dlx5 and wnt8b, was enhanced in xArx-injected embryos. Loss-of-function experiments indicated that xArx was necessary for normal forebrain development. Expansion of wnt8b expression depended on xArx function as a transcriptional repressor, whereas ectopic expression of dlx5, accompanied by development of ectopic otic structures, depended on function of Arx as a transcriptional activator. These results suggest that Arx acts as a bifunctional transcriptional regulator in brain development.

Animals↗
PubMed2003

N-(4-hydroxyphenyl)retinamide inhibits retinoblastoma growth through reactive oxygen species-mediated cell death.

Retinoblastoma arises from a subset of developing retinal cells lacking the RB-1 gene product pRB, which have lost the ability to respond to apoptotic signals. A better understanding of retinoblastoma biological response to therapeutic agents with low toxicity could improve the development of novel approaches for treatment and prevention of the disease. Naturally occurring retinoids inhibit growth and induce differentiation of Y79 human retinoblastoma cells in vitro. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) has been shown to induce apoptosis and/or necrosis of tumor cells of neuroectodermal origin. We examined the sensitivity of Y79 retinoblastoma cells to 4HPR in vitro, and in a xenograft model of tumor growth in nude mice in vivo. 4HPR treatment in the range 2.5 to 10 microM induced a loss of Y79 cell viability, as determined by crystal violet, trypan blue exclusion, and long-term clonogenic assays, and impairment of mitochondrial function detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Reactive oxygen species were elevated in 4HPR-treated cells and antioxidants rescued cell viability, indicating that 4HPR-induced cell death was mediated by oxidative stress. 4HPR inhibited growth of Y79 xenografts in vivo in both chemoprevention and intervention settings. Tumor growth inhibition by 4HPR was also associated with significant inhibition of angiogenesis in vivo. These findings could have an important translational value for chemoprevention or early intervention in the treatment of retinoblastoma.

Animals↗
PubMed1990

[Effect of pigmented epithelium from different developmental stages of chick embryo on cell growth of retinal explants].

The model system to investigate the effect of retinal pigmented epithelium (PE) on the retinal development in vitro has been established in this laboratory. Chick retina separated from 5-day-old embryo (E 5) were cut into strips and explanted on the collagen substratum either in close contact with retinal PE (RPE), or without PE (R). The rates of cell proliferation of retinal strips cultured for 48 hr were measured by the uptake of radioactive thymidine and DNA contents. Both parameters in RPE were increased to values ranging from 137 to 167% when PE was taken from E5 and E6. However PE taken from E7, E8 and E9 had no effect on cell proliferation. The rate of cell proliferation of retina were increased both when separated retina and PE of E5 either from same or from an other eye closely contact again and when retina and PE of E5 were explanted together without separation. However the rates of cell proliferation were remained without much change when a millipore filter existed between retina and PE of E5 as well as the retina was inverted, the ganglion cell layer contacted with PE. The neurite outgrowth from retina explant with and without PE of E5 or E6 were also different. After culture for 24 hr the fiber length of neurite growing in RPE was only 36-39% of that in R. After 48 hr it was about 70% of that in R. This results suggested that the developmental stage of PE and the direct cell-to-cell contact of PE from E5 with photoreceptor layer of retina was important for the retinal cell proliferation. But PE had negative influence on neurite growth of retina in culture.

Animals↗
PubMed2004

The first knockout mouse model of retinoblastoma.

The retinoblastoma susceptibility gene (RB1) was the first tumor suppressor gene identified in humans (Friend, et al., 1986) and the first tumor suppressor gene knocked out by targeted deletion in mice (Jacks, et al., Clarke, et al., Lee, et al., 1992). Children with a germline mutation in one of their RB1 alleles are likely to experience bilateral multifocal retinoblastoma; however, mice with a similar disruption of Rb1 do not develop retinoblastoma. The absence of a knock-out mouse model of retinoblastoma has slowed the progress toward developing new therapies and identifying secondary genetic lesions that occur after disruption of the Rb signaling pathway. Several advances have been made, over the past several years, in our understanding of the regulation of proliferation during retinal development (Zhang, et al., 2004; Dyer J, 2004; Dyer, Cepko, 2001) and we have built upon these earlier studies to generate the first nonchimeric knock-out mouse model of retinoblastoma. These mice are being used as a preclinical model to test new therapies for retinoblastoma and to elucidate the downstream genetic events that occur after inactivation of Rb1 or its related family members.

Animals↗
PubMed2005

[Risk factors of retinal redetachment after expected silicone oil removal].

PURPOSE: To analyze the clinical risk factors of the occurrence of retinal redetachment after expected silicone oil removal. METHODS: Clinical data were studied retrospectively. A total of 105 eyes of 104 consecutive patients were enrolled according to the criteria as follows: the expected intraocular silicone oil removal was performed after pars plana vitrectomy for complicated rhegmatogenous retinal detachment (RRD); the retina was flat during silicone oil tampanade; the patients were dealt with by the same surgeon. RESULTS: With a mean postoperative follow-up of 310 days, 11 of 105 eyes (10.4%) developed retinal redetachment after silicone oil removal. The redetachment rate was higher in the aphakic eyes (21.1%) than in the phakic/pseudophakic eyes (4.5%) (OR 5.69, P < 0.05). However, the factors, including giant tear, PVR grade C3 and D, previous failed retinal detachment surgery, high myopia, had no significance with retinal redetachment (Ps > 0.05). Among the 77 eyes undergoing prophylactic 360 degree laser retinopexy before silicone oil removal, 4 eyes had retinal redetachment (5.2%). The redetachment ratio was lower than those without prophylactic laser retinopexy (OR 0.16, P < 0.05). CONCLUSION: Aphakia is a risk factor of retinal detachment after removal of silicone oil. Prophylactic 360 degree laser retinopexy can reduce the incidence of retinal redetachment.

Adolescent↗
PubMed1988

Retinopathy of prematurity.

Increasing numbers of immature infants are surviving with incompletely developed retinal vessels at risk for ROP. Since adverse perinatal events seem closely associated with the more severe forms of the disorder, neonatologists may be able to contribute most to the reduction of vision loss if they can optimize the neonatal course of these infants. However, to date, no particular intervention has been proven to be efficacious in preventing ROP. On the other hand, cryotherapy has been found effective in stopping the progress of severe ROP to retinal detachments about half the time. This places a responsibility on the neonatologist and ophthalmologist to assure that each at-risk infant is examined by 4-6 weeks of age to enable the prompt application of cryotherapy if severe ROP develops. This is presently the infant's best chance of retaining useful vision, and appropriate nursery policies should be developed to ensure its availability. Additional research is needed to understand the control of regression vs progression in ROP and to explore potential means of preventing the disease altogether.

Birth Weight↗
PubMed2004

Spatial and temporal patterns of apoptosis during differentiation of the retina in the turtle.

We investigated patterns of cell death in the turtle retina that could potentially be associated with the innervation of the optic tectum, and looked for mechanisms of retinal development that might be common to reptilian and homeotherm vertebrates. We used retinas of turtle embryos between the 23rd day of incubation (E23) (before the first optic fibres reach the optic tectum) and hatching (when all the optic fibres have established synaptic connections). Dying retinal neurons were identified in paraffin sections by the TUNEL technique, which specifically labels fragmented DNA. Apoptotic cells were found in the ganglion cell layer (GCL), the inner nuclear layer (INL), and the outer nuclear layer (ONL). Cell death in the GCL was intense between E29 and E47, and had disappeared by the day of hatching. In the INL, dead and dying cells were most abundant between E31 and E34, and progressively disappeared. The temporal pattern in the ONL was similar to the INL although the density was very low. In all the nuclear layers cell death spread from the dorso-temporal area of the central retina to the periphery. Additional dorsal to ventral and temporal to nasal gradients were distinguishable in a quantitative TUNEL analysis. The patterns of cell death observed in the developing turtle retina were thus similar to those found in birds and mammals. This process could be under the control of differentiation gradients in all the vertebrate classes.

Animals↗
PubMed1996

What do developmental mapping rules optimize?

Convergence ratios between pre- and postsynaptic cells in the visual system vary widely between cell classes, areas of the visual field, between individuals and between species. Proper stabilization of the convergence and divergence of single visual neurons is critical for visual integration generally, and for specific functions such as those of rod and cone pathways, or the center and peripheral regions of the visual field. In early development, retinal ganglion cells, target cells and all their processes are produced in excess and stabilize at certain mature values. The intent of the investigations described here is to determine what features of cell connectivity are stabilized over normal variability by these developmental processes and how such stabilization is accomplished, using the developing mammalian retinotectal system as an example. Orderly compression of the retinotopic map into a half tectum was induced by a partial tectal ablation at birth in hamsters, increasing the ratio of retinal ganglion cells to superior colliculus target cells. The convergence problem is solved in this case by undersampling the spatial array with respect to normal, preserving local spatial resolution, but potentially reducing sensitivity or introducing aliasing artifacts. Receptive field sizes of single neurons are indistinguishable from normal, and reduction of branching of presynaptic axon arbors is the mechanism of the remapping. Behaviorally, though the entire visual field is still represented in the remaining colliculus, the solution has a cost in decreased probability and increased latency to orient to visual stimuli, particularly in the peripheral visual field. The generality of this solution for retinal and other central convergence regulation problems is evaluated.

Animals↗
PubMed1997

Famciclovir for the treatment of acute retinal necrosis (ARN) syndrome.

PURPOSE: To document a case of acute retinal necrosis syndrome in an immunocompetent patient who was successfully treated with famciclovir after unsuccessful treatment with acyclovir. METHODS: After diagnosing acute retinal necrosis syndrome in the patient's left eye, we treated him with 13 mg/kg/24 hours of intravenous acyclovir in three daily doses for 14 days, followed by 800 mg of acyclovir five times per day orally. New areas of retinitis developed within the posterior pole despite treatment with the maximum dosage of acyclovir; thus, we used a new antiviral agent, famciclovir. RESULTS: When we administered 500 mg of famciclovir orally every 8 hours for 3 months, the retinitis regressed within 1 month, leaving atrophic granular pigmented scars. CONCLUSION: Famciclovir can effectively treat acute retinal necrosis syndrome in immunocompetent patients.

2-Aminopurine↗
PubMed1982

Prophylactic argon laser photocoagulation in retinal detachment fellow eyes.

Over a two-year period (1975-76) 329 patients were operated for rhegmatogenous retinal detachment. 301 patients had unilateral detachment and in 62 of these prophylactic photocoagulation with argon laser in the fellow eye was performed. During the observation time one of these (1.6%) and 7 untreated (2.9%) fellow eyes developed retinal detachment. The indication for prophylactic photocoagulation of fellow eyes and the results are discussed.

Adult↗
PubMed1993

Cytomegalovirus retinitis under combination therapy with zidovudine and dideoxycytidine in advanced human immunodeficiency virus infection.

The incidence of cytomegalovirus (CMV) retinitis during combination therapy with zidovudine (azidothymidine AZT) and zalcitabine (dideoxycytidine ddC), was compared with that during monotherapy with AZT alone in patients with advanced human immunodeficiency virus (HIV) infection. A total of 85 patients with CD4 cell counts under 500/microliters were enrolled in a prospective, controlled study. Between August 1991 and June 1992, these patients were treated daily with 500 mg/kg AZT given alone (n = 42) or in combination with 0.02 mg/kg ddC (n = 43). The rate of occurrence of typical microvascular retinopathy with cotton-wool exudates was lower in patients receiving combination treatment than in those given monotherapy [10 patients (26%) receiving AZT/ddC vs 23 patients (56%) given AZT; P < or = 0.01, chi-square test]. CMV retinitis developed in 8 patients (19%) treated with AZT and in 6 patients (14%) treated with ddC and AZT (no significant difference). In contrast to recently published data, we found no decrease in the rate of occurrence of retinitis in the group under combined antiretroviral therapy but observed a significantly lower incidence of microvascular retinopathy.

AIDS-Related Opportunistic Infections↗
PubMed1995

Changes in retinal cell fate induced by overexpression of EGF receptor.

The differentiation of multipotential progenitor cells in the vertebrate retina into photoreceptors, neurons and glial cells is regulated in part by cell-cell signalling. Transforming growth factor (TGF)-alpha is one of the extracellular signals implicated in the control of several aspects of retinal development, including proliferation and cell fate. The way cells interpret pleiotropic signals such as TGF-alpha is influenced by the level of expression of epidermal growth factor receptor (EGF-R) in some cell lines. To address the influence of receptor level on responses of retinal progenitor cells to TGF-alpha, additional copies of EGF-Rs were introduced in vitro and in vivo with a retrovirus. Normally in vitro, low concentrations of TGF-alpha stimulated proliferation whereas high concentrations biased choice of cell fate, inhibiting differentiation into rod photoreceptors while promoting differentiation into Müller glial cells. We report here that introduction of extra EGF-Rs into progenitor cells in vitro reduced the concentration of TGF-alpha required for changes in rod and Müller cell differentiation but did not enhance proliferation. Introduction of extra EGF-Rs in vivo increased the proportion of clones that contained Müller glial cells, suggesting that receptor level is normally limiting. These findings demonstrate that responsiveness to extracellular signals during development can be modulated by the introduction of additional receptors, and suggest that the level of expression of receptors for these signals contributes to the regulation of cell fate.

Animals↗
PubMed1991

Immortalized retinal neurons used as immunogen for the generation of cell-specific antisera.

We have recently described a class of immortalized neurons which were derived from retinal tumors induced in PNMT-SV40 transgenic mice (TgBri59)9. These neurons possess a differentiated neuronal phenotype which includes the elaboration of extensive neurite processes and the expression of markers specific for amacrine and horizontal neurons, as well as the expression of the neurofilament triplet proteins. As these 'RT-1' neurons are derived from a restricted set of retinal neurons, they represent an enriched source of immunogen for the production of cell-specific antisera. Therefore, we have used RT-1 cell cultures to generate polyclonal antisera in rabbits. Two of these antisera have been characterized in immunocytochemical and Western blotting experiments using normal mouse and rat tissues. The antisera recognize neurons in the inner nuclear layer and particularly in the ganglion cell layer in the normal retina and cells of the adrenal medulla. These data indicate that specific cell lines derived from transgenic animals provide a rich source of antigen for the production of cell-specific antibodies. These antibodies should prove valuable for studies of retinal development and function.

Animals↗
PubMed1991

Anatomical correlations between soma size, axon diameter, and intraretinal length for the alpha ganglion cells of the cat retina.

Retinal ganglion cells within the same region of the retina may have different lengths of axon before reaching the optic disc depending on the route they take with respect to the temporal raphe. We have investigated whether there is a correlation between soma and intraretinal axon diameter and how these parameters relate to intraretinal axon length on both sides of the cat temporal raphe. Retinas were wholemounted and alpha-cell somata and fibers stained with a modified neurofibrillar method. Moving peripherally from the area centralis along the raphe there was a progressively increasing difference between the intraretinal axon lengths for nearly adjacent cells across the raphe, which reached a maximum of 4-5 mm at the retinal periphery. Cells on the nasal aspect of the raphe had shorter axons than did adjacent cells on the temporal aspect of the raphe. Comparison of soma diameter samples across the raphe showed there was no clear trend between soma diameter and intraretinal length. Replotting the raphe and sample areas on a cell density map indicated that differences in soma diameter could be attributed to ganglion-cell density differences between the sampled areas. Examination of the stained cells revealed that within the initial length of the axon there was a region showing a reduction of axon diameter (diameter less than 1 micron), which varied in length from cell to cell. The axon was, therefore, divided into three segments: the portion of axon prior to thinning (A), the thin segment itself (B), and the part of the axon after the thin segment (C). The diameter of each segment (A,B,C) and the lengths of the first and second segments (A,B) were significantly correlated with soma diameter (P less than 0.001). From measurements of the axon diameter of segment C, it was concluded that alpha-cell axons continue to increase in diameter along their path towards the optic disc. The present report indicates that alpha-cell soma size, when going from the area centralis to the periphery along the raphe, reaches a plateau and then declines within more peripheral retinal locations in spite of increasing intraretinal axon length. Thus, there is no positive correlation between soma or axon diameter and intraretinal axon length. The anatomical findings are discussed in relation to previous reports of retinal development and complementary conduction times within intraretinal and extraretinal visual pathways.

Animals↗
PubMed1986

Light damage in the developing retina of the albino rat: an electroretinographic study.

The albino rat retina is severely damaged by exposure to bright light. The degree of damage depends upon the intensity of the exposure and its duration. In the present study, electroretinographic (ERG) responses were measured in rats exposed at different ages during the period of retinal development to 24 hr of bright light and then transferred to darkness for about 2 months. The ERG data indicated that if the bright-light exposure was done prior to 20 days of age, the retina was resistant to the light damage, and the dark-adapted ERG responses measured later were normal. In rats older than 20 days, light damage increased with age until, in rats exposed to light at age 30 days, the ERG was unrecordable. Further experiments showed that light exposure did damage the 15-day-old rat retina; however, complete recovery was attained within 15 days postexposure.

Aging↗