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 253 records · Page 14Linked to original sources
PubMed2000

Neuronal and inducible nitric oxide synthase distribution in retinas of microphthalmic mice.

A study about the distribution of neuronal nitric oxide synthase (n-NOS) and inducible NOS (i-NOS) was performed in microphthalmic retinas at postnatal day (pd) 2 and pd 7. Neither n-NOS nor i-NOS immunoresponse could be detected at pd 2. At pd 7, i-NOS activity was revealed in the retinas of mi/mi littermates but not in those of heterozygotes or wild-type littermates. The expression of n-NOS corresponded to the postnatal retinal development. Retinal rosettes were strongly labelled.

Animals↗
PubMed1985

Rhegmatogenous retinal detachment in Labrador retrievers. I. Development of retinal tears and detachment.

We used clinical and pathologic methods to examine ten Labrador retrievers with ocular and skeletal abnormalities. The major ocular findings were axial myopia; cataract; vitreous abnormalities, including liquefaction, detachment, and vitreoretinal traction; retinal tears; rhegmatogenous retinal detachment; and proliferative vitreoretinopathy. The appendicular skeleton showed retarded bone growth, bone dysplasia, and degenerative arthropathy. Vitreoretinal traction appeared to be the cause of the retinal tears because (1) formed vitreous was always attached near the anterior edge of the tear, and (2) vitreous traction caused a retinal ridge adjacent to a retinal tear in a dog that had not yet developed retinal detachment. The pathogenetic sequence of spontaneous vitreous abnormalities, retinal tears, and retinal detachment observed in these dogs has not previously been described in animals, to the best of our knowledge, and mimicked human rhegmatogenous retinal detachment, particularly those associated with giant retinal tears.

Animals↗
PubMed2005

Attenuation of retinal vascular development and neovascularization during oxygen-induced ischemic retinopathy in Bcl-2-/- mice.

Bcl-2 is a death repressor that protects cells from apoptosis mediated by a variety of stimuli. Bcl-2 expression is regulated by both pro- and anti-angiogenic factors; thus, it may play a central role during angiogenesis. However, the role of bcl-2 in vascular development and growth of new vessels requires further delineation. In this study, we investigated the physiological role of bcl-2 in development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Mice deficient in bcl-2 exhibited a significant decrease in retinal vascular density compared to wild-type mice. This was attributed to a decreased number of endothelial cells and pericytes in retinas from bcl-2-/- mice. We observed, in bcl-2-/- mice, delayed development of retinal vasculature and remodeling, and a significant decrease in the number of major arteries, which branch off from near the optic nerve. Interestingly, hyaloid vessel regression, an apoptosis-dependent process, was not affected in the absence of bcl-2. The retinal vasculature of bcl-2-/- mice exhibited a similar sensitivity to hyperoxia-mediated vessel obliteration compared to wild-type mice during OIR. However, the degree of ischemia-induced retinal neovascularization was significantly reduced in bcl-2-/- mice. These results suggest that expression of bcl-2 is required for appropriate development of retinal vasculature as well as its neovascularization during OIR.

Aging↗
PubMed2003

The roles of Hedgehogs and Fibroblast Growth Factors in eye development and retinal cell rescue.

Knowledge of normal eye development is crucial for the development of retinal rescue strategies. I shall focus on two signalling pathways that affect retinal development. Fibroblast growth factors function in retinal cell proliferation, retinal ganglion cell axon guidance and target recognition, craniofacial patterning and lens induction. Hedgehog proteins are required for progression of the neurogenic wave, cell proliferation, photoreceptor differentiation, retinal ganglion cell axon growth and craniofacial patterning. These signalling pathways have pleiotropic effects, can interact and have the potential to be used therapeutically. The zebrafish model organism may be well suited to studying how signalling pathways interact.

Animals↗
PubMed1998

Activation and inactivation properties of voltage-gated calcium currents in developing cat retinal ganglion cells.

The correlated activity of developing retinal ganglion cells is essential for the reorganization and refinement of retinogeniculate projections. Previous studies have uncovered marked changes in the spiking properties of retinal ganglion cells during this period of reorganization; however, a full understanding of the changes in the underlying ionic conductances has yet to be obtained. To this end, the whole-cell configuration of the patch-clamp technique was used to record currents conducted by voltage-gated calcium channels in 83 dissociated cat retinal ganglion cells obtained from animals aged between embryonic day 34 and postnatal day 105. Calcium currents, magnified by using barium as the major charge carrier, were isolated by substituting choline for Na+ in the bathing solution and Cs+ for K+ in the electrode solution. Three voltage-gated Ca2+ conductances were identified based on their voltage dependence and kinetics of activation and inactivation: a transient low-voltage-activated conductance, a transient high-voltage-activated conductance and a sustained high-voltage-activated conductance. During the developmental period examined there were significant increases in the densities of all three conductances, as well as significant changes in some of their activation and inactivation properties. These findings, together with those reported previously for the voltage-gated Na+ and K+ conductances, are related to the generation of excitability in developing retinal ganglion cells during a period critical to the normal development of the visual system. Furthermore, while the sustained high-voltage-activated conductance was present in all of the retinal ganglion cells observed, only about 72% expressed the transient high-voltage-activated current. During the developmental period examined, there was also an increase in the proportion of cells expressing the transient low-voltage-activated conductance. This, along with our previous finding that retinal ganglion cells heterogeneously express different types of voltage-gated K+ channels, strongly suggests that the spiking patterns observed in different classes of retinal ganglion cell may be due, in part, to their intrinsic membrane properties.

Animals↗
PubMed1990

Analysis of adenosine immunoreactivity, uptake, and release in purified cultures of developing chick embryo retinal neurons and photoreceptors.

We have investigated the presence of endogenous adenosine and of mechanisms for adenosine uptake and release in chick embryo retinal neurons and photoreceptors grown in purified cultures in the absence of glial cells. Simultaneous autoradiographic and immunocytochemical analysis showed that endogenous adenosine and the uptake mechanism for this nucleoside colocalize in practically all the photoreceptors, but only in approximately 20% of the neurons. Approximately 25% of the neurons showed either immunocytochemical labeling or autoradiographic labeling, while greater than 50% of the neurons were unlabeled with both techniques. [3H]Adenosine uptake was saturable and could be inhibited by nitrobenzylthioinosine and dipyridamole and by pretreatment of the [3H]adenosine with adenosine deaminase. Although these observations indicate that the uptake is specific for adenosine, only 35% of accumulated radioactivity was associated with adenosine, with the remaining 65% representing inosine, hypoxanthine, and nucleotides plus uric acid. Adenosine as well as several of its metabolites were released by the cells under basal as well as K(+)-stimulated conditions. Potassium-enhanced release was blocked by 10 mM CoCl2 or in Ca2(+)-free, Mg2(+)-rich solutions. The results indicate that retinal cells that synthesize, store, and release adenosine differentiate early during embryogenesis and are therefore consistent with a hypothetical role for adenosine in retinal development.

Adenosine↗
PubMed1997

Differentiation and morphogenesis in pellet cultures of developing rat retinal cells.

We previously developed a reaggregate cell culture system (pellet cultures) in which retinal neuroepithelial cells proliferate and give rise to rod photoreceptor cells (rods) in vitro (Watanabe and Raff, 1990, Neuron 4:461-467). In the present study, we analyzed cell differentiation and morphogenesis in pellet cultures by using both cell-type-specific markers with immunofluorescence and electron microscopy. We demonstrated that, in addition to rods, the other major retinal cell types, including amacrine cells, bipolar cells, Müller cells, and ganglion cells were all present in the pellets, where most were able to develop from dividing precursor cells in vitro. The different cell types in the pellets became organized into two distinct structures: dark rosettes and pale rosettes. The cellular composition of these structures indicated that the dark rosettes correspond to the outer nuclear layer and the pale rosettes to the inner nuclear layer of the normal retina. Ultrastructural studies have indicated that the thin layer of neuronal processes surrounding the dark rosettes correspond to the outer plexiform layer, and the central region of the pale rosettes correspond to the inner plexiform layer of the normal retina. Other features of normal retinal development also occurred in the pellets, including programmed cell death and the formation of inner and outer rod cell segments and synapses. Thus, pellet cultures provide a convenient way to study different aspects of retinal development where one can control the size and the cellular composition of the initial reaggregate.

Animals↗
PubMed1985

Postnatal retinal vascular development of the puppy.

Retinal vascular development during the first three postnatal weeks was studied in 63 purebred beagle puppies. Use of a positive enzyme histochemical reaction for adenosine triphosphatase in the nuclei and nucleoli of vascular cells made visualization of the retinal vasculature possible. Animals were killed by decapitation. Thus, artifacts resulting from use of anesthetics or tracer substances were avoided. In general, this study demonstrates important similarities between canine and human retinal vascular development, and this gives further reason to use of the puppy retina as a superior model for studying retrolental fibroplasia pathogenesis. This staining technique demonstrates undifferentiated cells in the avascular retina that appear to be vascular precursors or angioblasts. Primordial vessels form by organization of differentiating angioblasts that exist in peripheral retinal cystic spaces at birth, or by addition of fully differentiated endothelium; they form unlike neovascularization. Müller cell processes appear to provide a structural matrix throughout the avascular puppy retina on which differentiated angioblasts organize into a vascular network. Arteries develop in beds of primordial capillaries lying near the leading edge of the developing vasculature. This precedes vein formation which occurs through a process involving coalescence of embryonic capillaries which themselves were derived from primordial capillaries. Preliminary examination of eight mongrel kitten retinas prepared by this method clearly indicates that the puppy retina is much more completely vascularized at birth than that of the newborn kitten. Moreover, the rate of postnatal retinal vascularization is significantly faster in the kitten. The kitten vasculature does appear to form by the organization of angioblasts as in the puppy, but kitten angioblasts have a different appearance from those in the puppy.

Adenosine Triphosphatases↗
PubMed1994

CMV-specific immune responses and HLA phenotypes of AIDS patients who develop CMV retinitis. HNRC Group. HIV Neurobehavioral Research Center.

HLA phenotype and immune responses to CMV were studied to determine whether the subset of AIDS patients who developed CMV retinitis were immunogenetically or immunologically predisposed. CMV retinitis develops in approximately 28-35% of AIDS patients and CMV encephalitis develops in 40% of those with retinitis, often leading to death. T-cell proliferation responses to CMV and HIV were assayed prospectively in individuals enrolled in a longitudinal study at the HIV Neurobehavioral Research Center (HNRC) in San Diego. Seventy-three participants, at various stages of disease, have been HLA typed and followed, clinically and immunologically, for up to 5 years. Six HIV infected individuals who eventually developed CMV retinitis, and were assayed prospectively, had a history of low T-cell proliferation to CMV antigens before they were profoundly immunosuppressed. All 10 individuals with CMV retinitis had at least one of three HLA alleles (or combinations): A2B44 (p = 0.02), B51(p = 0.02), or DR7 (p = 0.01) (collective p value = 0.007). Three of the 10 had two or more of these alleles. Of AIDS patients with CD4 counts below 100 and actively at risk for retinitis, 7/15 with A2B44,51, or DR7 have developed retinitis compared to 0/13 without these HLA alleles (relative risk = 23.8). All 4 patients with these alleles who have died, had retinitis. These results suggest that HIV infected individuals with HLA phenotypes A2B44, B51, and DR7 have low T-cell immune responses to CMV and are predisposed to CMV retinitis and encephalitis as immunodeficiency progresses.

AIDS-Related Opportunistic Infections↗
PubMed2004

Retinal replacement--the development of microelectronic retinal prostheses--experience with subretinal implants and new aspects.

BACKGROUND: Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. Different concepts of retinal replacement are currently under investigation. The aim of the retinal prostheses is to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa. METHODS: Within the field of visual prosthetic developments mainly two retinal based concepts are under investigation. One of the concepts is the epiretinal implant which acquires images of an external camera and after preprocessing by a computer reading this visual information into the human visual system. In the subretinal prosthesis design concept an array of stimulation electrodes is placed in the subretinal space. True to the concept the image falling on the retina and its light impulses are converted into electrical currents by microphotodiodes and the retina is stimulated with these locally. To test the feasibility of the concepts the biocompatibility and to determine basic stimulation parameters a lot of animal experiments and first human experiments were carried out. RESULTS: Currently the research conducted by teams in Germany, the USA and Japan into epiretinal and subretinal implants has reached the stage where clinical trials can now be performed. Individual pilot studies were carried out for both the epiretinal and the subretinal implant by different research groups. DISCUSSION: The results achieved by the researchers indicate that cortical action potentials can be triggered by electric retinal stimulation with both concepts. The experimental work has highlighted a whole range of obstacles, not all of which have yet been fully resolved. These findings offer hope that coarse restoration of vision may be feasible by electrical stimulation.

Animals↗
PubMed2003

Cellular mechanisms in retinal vascular development.

Since the pioneering work of Ashton and others, the primate retina has been thought to vascularize by a vasculogenic linkage of endothelial precursor cells. Recent investigations using specific histologic and morphologic criteria question the contribution of vasculogenesis to retinal development. Instead, in primates and mice cells previously designated as retinal angioblasts have been identified as astrocytes that form a vascular-like plexus preceding vessel invasion. Further, in primates and mice retinal vascularization proceeds via angiogenic sprouting from pre-existing vessels in all regions and stages. However, the developing retinal vasculature may utilize novel sources of endothelial cells, such as recruitment of circulating stem cells and redeployment of mural cells from regressing vessel segments. These results provide a framework for study of retinal vascular development, validate the common use of perinatal retinal models in angiogenesis research, and clarify the cellular basis of retinopathy of prematurity.

Animals↗
PubMed2004

Global gene expression analysis of the developing postnatal mouse retina.

PURPOSE: Postnatal mouse retinal development involves glial and neuronal differentiation, vascularization, and the onset of vision. In the current study, the gene expression profiles of thousands of genes in the developing postnatal mouse retina were analyzed and compared in a large-scale, unbiased microarray gene expression analysis. METHODS: For each of eight different time points during postnatal mouse retinal development, two separate sets of 30 retinas were pooled for RNA isolation, and gene expression was analyzed by hybridization to gene chips in triplicate (Mu74Av2; Affymetrix, Santa Clara, CA). Genes were sorted into clusters based on their expression profiles and intensities. Validation was accomplished by comparing the microarray expression profiles with real-time RT-PCR analysis of selected genes and by comparing selected expression profiles with predicted profiles based on previous studies. RESULTS: The Mu74Av2 chip contains more than 6000 known genes and 6500 estimated sequence tags (ESTs) from the mouse Unigene database. Of these, 2635 known gene sequences and 2794 ESTs were expressed at least threefold above background levels during retinal development. Expressed genes were clustered based on expression profiles allowing potential functions for specific genes during retinal development to be inferred by comparison to developmental events occurring at each time point. Specific data and potential functions for genes with various profiles are discussed. All data can be viewed online at http://www.scripps.edu/cb/friedlander/gene_expression/. CONCLUSIONS: Expression analysis of thousands of different genes during normal postnatal mouse retinal development as reported in this study demonstrates that such an approach can be used to correlate gene expression with known functional differentiation, presenting the opportunity to infer functional correlates between gene expression and specific postnatal developmental events.

Animals↗
PubMed2006

Retinal functional development is sensitive to environmental enrichment: a role for BDNF.

Retina has long been considered less plastic than cortex or hippocampus, the very sites of experience-dependent plasticity. Now, we show that retinal development is responsive to the experience provided by an enriched environment (EE): the maturation of retinal acuity, which is a sensitive index of retinal circuitry development, is strongly accelerated in EE rats. This effect is present also in rats exposed to EE up to P10, that is before eye opening, suggesting that factors sufficient to trigger retinal acuity development are affected by EE during the first days of life. Brain derived neurotrophic factor (BDNF) is precociously expressed in the ganglion cell layer of EE with respect to non-EE rats and reduction of BDNF expression in EE animals counteracts EE effects on retinal acuity. Thus, EE controls the development of retinal circuitry, and this action depends on retinal BDNF expression.

Animals↗
PubMed2001

[Cloning the differentially expressed genes in the retina of rds mouse during the development of retinitis pigmentosa].

OBJECTIVE: To clone the differentially expressed genes in the retina of rds mouse (the animal model of congenital retinitis pigmentosa) during the disease development. METHODS: The retinal mRNA of rds mouse during the development of retinitis pigmentosa was analyzed by the mRNA differential display. The differentially expressed mRNA fragments were cloned and sequenced. RESULTS: There was obvious difference of gene expression between rds mouse and the control during the development of retinitis pigmentosa. Five differentially expressed bands were cloned and sequenced. One of those had 86% identity (132/154) with the sequence of the human cDNA DKFZp434D1227 from adult testis in GenBank, which was submitted lately (15-Oct-1999) and without much information. The other had lower identity with the sequences in GenBank. A highly expressed clone in the rds mouse on postnatal day 25 had the same length as another clone in the normal on postnatal day 37, which was not expressed in the rds mouse on day 37. The sequences of the two clones were identical in all but two base pairs. CONCLUSION: These results indicate that there are a lot of novel differentially expressed genes in the chronic processing diseases, such as retinitis pigmentosa.

Animals↗
PubMed2000

Expression of GABA(C) receptor rho1 and rho2 subunits during development of the mouse retina.

Retinal gamma-aminobutyric acid type C (GABA(C)) receptors consist of rho subunits. Here we report our results from a competitive PCR and patch-clamp electrophysiology study quantifying rho subunit message and characterizing GABA(C) receptor-mediated currents at different stages of mouse retinal development. Mouse rho1 message is first detected at postnatal day 6 (P6), increases significantly until P9 and remains at this level through adulthood, whereas mouse rho2 message does not appear until P9, peaks at P15 and remains at this level through adulthood. There is an approximate twofold excess of rho1 compared to rho2 message at most stages of development, which persists in adulthood. Functional GABA(C) receptors are detected in acutely dissociated bipolar cells of P9 or older mouse retina. Early in development (P9-10), GABA(C) receptors are composed solely of rho1 subunits, but subsequently contain rho1 and/or rho2 subunits (by P11 and later). These findings are intriguing because the onset and rapid increase in rho subunit transcription and functional expression match the initiation and active period of bipolar cell differentiation in retinal development as well as the stage of eye opening and initial visual experience in the rodent. The investigation of mouse rho subunits here forms a basis for future studies on the role of GABA(C) receptors in retinal development.

Age Factors↗
PubMed2000

A role for voltage-gated potassium channels in the outgrowth of retinal axons in the developing visual system.

Neural activity is important for establishing proper connectivity in the developing visual system. Tetrodotoxin blockade of sodium (Na(+))-dependent action potentials impairs the refining of synaptic connections made by developing retinal ganglion cells (RGCs), but does not affect their ability to get out to their target. Although this may suggest neural activity is not required for the directed extension of RGC axons, in many species developing RGCs express additional, Na(+)-independent ionic mechanisms. To test whether the ability of RGC axons to extend in a directed fashion is influenced by membrane excitability, we blocked the principal modulators of the neural activity of a neuron, voltage-dependent potassium (Kv) channels. First, we showed that RGCs and their growth cones express Kv channels when they are growing through the brain on the way to their main midbrain target, the optic tectum. Second, a Kv channel blocker, 4-aminopyridine (4-AP), was applied to the developing Xenopus optic projection. Blocking Kv channels inhibited RGC axon extension and caused aberrant routing of many RGC fibers. With the higher doses, <25% of embryos had a normal optic projection. These data suggest that Kv channel activity regulates the guidance of growing axons in the vertebrate brain.

4-Aminopyridine↗
PubMed1998

Risk of developing CMV retinitis following non-ocular CMV end organ disease in AIDS patients.

AIM: To describe the risk of developing cytomegalovirus (CMV) retinitis after a first episode of extraocular CMV disease in AIDS patients. METHODS: A review of the clinical records of 20 AIDS patients, without CMV retinitis, with histologically confirmed extraocular CMV disease, was performed. The main outcome measures were occurrence of CMV retinitis, time to development of CMV retinitis, relation to maintenance therapy, and survival. RESULTS: A CMV retinitis was diagnosed in 17 of 20 (85%) patients with an immunohistologically confirmed diagnosis of extraocular CMV disease after a mean follow up of 6.4 months. Four patients received maintenance therapy. Three of them developed retinitis after a mean of 9.6 months (range 2-16 months). Sixteen did not receive maintenance and retinitis was diagnosed in 14 of them after a mean of 5.7 months (range 2-11 months). Mean survival was 9.9 months after the diagnosis of extraocular disease, and 4.5 months after the diagnosis of retinitis. In the four patients receiving maintenance therapy, mean survival was 11.5 months, and in the 16 other patients mean survival was 9.5 months. Patients did not receive protease inhibitors. CONCLUSION: In the preprotease inhibitor era extraocular CMV disease strongly predisposes to the subsequent development of CMV retinitis. Although maintenance therapy did not prevent the occurrence of retinitis, the time period between both events seems to lengthen considerably. In patients receiving maintenance survival is also longer.

AIDS-Related Opportunistic Infections↗
PubMed2003

Invariant Sema5A inhibition serves an ensheathing function during optic nerve development.

Retinal axon pathfinding from the retina into the optic nerve involves the growth promoting axon guidance molecules L1, laminin and netrin 1, each of which governs axon behavior at specific regions along the retinal pathway. In identifying additional molecules regulating this process during embryonic mouse development, we found that transmembrane Semaphorin5A mRNA and protein was specifically expressed in neuroepithelial cells surrounding retinal axons at the optic disc and along the optic nerve. Given that growth cone responses to a specific guidance molecule can be altered by co-exposure to a second guidance cue, we examined whether retinal axon responses to Sema5A were modulated by other guidance signals axons encountered along the retinal pathway. In growth cone collapse, substratum choice and neurite outgrowth assays, Sema5A triggered an invariant inhibitory response in the context of L1, laminin, or netrin 1 signaling, suggesting that Sema5A inhibited retinal axons throughout their course at the optic disc and nerve. Antibody-perturbation studies in living embryo preparations showed that blocking of Sema5A function led to retinal axons straying out of the optic nerve bundle, indicating that Sema5A normally helped ensheath the retinal pathway. Thus, development of some CNS nerves requires inhibitory sheaths to maintain integrity. Furthermore, this function is accomplished using molecules such as Sema5A that exhibit conserved inhibitory responses in the presence of co-impinging signals from multiple families of guidance molecules.

Animals↗