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Results for “retinal development”

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At least 1,009 records · Page 56Linked to original sources
PubMed2005

[Retinopathy during interferon treatment in combination with ribavirin for chronic hepatitis C].

PURPOSE: To observe the retinopathy of the patients who received interferon/ribavirin for treatment of chronic hepatitis C. METHODS: We observed 6 patients(5 males and 1 female) who received interferon/ribavirin for treatment of chronic hepatitis C. Visual acuity tests and detailed fundus examinations were performed monthly during 6 months of interferon/ribavirin therapy. RESULTS: All patients developed soft retinal exudate and 5 developed retinal blot hemorrhage. None of the patients exhibited visual impairment or subjective symptoms during the treatment period, and the retinopathy disappeared or decreased in all patients. All of the patients in this study developed interferon retinopathy while undergoing interferon/ribavirin combination therapy. CONCLUSION: Because the combination of ribavirin with interferon may increase the incidence of interferon retinopathy, and cases of severe retinal complications have also been reported, careful fundus examinations should be performed during combination therapy, just as they are performed during conventional interferon therapy.

Aged↗
PubMed2005

Expression and possible function of fibroblast growth factor 9 (FGF9) and its cognate receptors FGFR2 and FGFR3 in postnatal and adult retina.

Fibroblast growth factors (FGFs) are important regulators of retinal development and survival. We examined the expression and distribution of FGF9 and its preferred receptors FGFR2IIIc and FGFR3IIIc in this tissue. FGF9 transcripts in whole rat retina were detected by RT-PCR but were not present in purified cultured Muller glia. Transcripts appeared as 3.2-kb and 4.0-kb bands on Northern blots, and Western blotting of whole retina revealed FGF9-immunoreactive bands at 30 and 55 kDa. FGF9 mRNA demonstrated a biphasic expression profile, elevated at birth and adulthood, but relatively decreased during terminal retinal differentiation (4-14 days postnatal). Antibody labeling broadly reflected these findings: staining in vivo was observed mainly in the inner retina (and outer plexiform layer in adults) whereas FGF9 was not detectable in cultured Muller glia. In adults, FGF9 in situ hybridization also showed a detectable signal in inner retina. FGFR2IIIc and FGFR3IIIc were detected by RT-PCR, and Western blotting showed both FGFRs existed as multiple forms between approximately 100-200 kDa. FGFR2 and FGFR3 antibodies showed prominent labeling in the inner retina, especially in proliferating cultured Muller glia. Exogenous FGF9 elicited a dose-dependent increase in Muller glial proliferation in vitro. These data suggest a role for FGF9 in retinal differentiation and maturation, possibly representing a neuronally derived factor acting upon glial (and other) cells.

Aging↗
PubMed2004

Photodynamic therapy for retinal angiomatous proliferations and pigment epithelium detachment.

PURPOSE: To evaluate results of photodynamic therapy (PDT) with verteporfin for subfoveal neovascular age-related macular degeneration (ARMD) with retinal angiomatous proliferation (RAP) and pigment epithelial detachment (PED). DESIGN: Interventional case series. METHODS: Thirteen eyes (11 stage 2 and 2 stage 3 RAP) underwent PDT. Best-corrected visual acuity (BCVA), fluorescein and indocyanine-green angiography were performed to evaluate the outcome. RESULTS: After 13.5 +/- 2.5 months and 1.7 +/- 0.4 treatments, mean BCVA decreased from 20/73 to 20/174 (P = .04). Occlusion of RAP and flattening of PED was observed in three eyes, and persistence of PED in six. Two eyes deteriorated to disciform lesions, one developed hemorrhagic PED, and one evolved toward stage 3 RAP. Three eyes, with PED exceeding 50% of the entire lesion, developed retinal pigment epithelium tear. CONCLUSIONS: PDT might prove effective for neovascular ARMD with RAP and small PED, whereas it might cause acute retinal pigment epithelium tear for RAP with PED exceeding 50% of the lesion.

Aged↗
PubMedDate not supplied

[Problems and outlooks for the preventive treatment of retinopathy in prematures].

The immediate and remote (up to 7 years) results of preventive cryo- and/or lasercoagulation of avascular retinal zones made in 390 children with active progressing retinopathy of prematures (RP) were analyzed. The efficiency of cryocoagulation in processes localized in zones 2-3 of the eye bottom made 92%, and that of the combined technique (laser- and cryocoagulation) with lesions in zones 1-2 and with plus-diseases was up to 80%. The preventive treatment is indicated for the 3d threshold (ordinary clinical course) and before-threshold (with plus-disease and localization zone 1) stages. Such treatment is not justified when undertaken early and in developed retinal detachment. Further research of the disease pathogenesis is needed to enhance the efficiency of the RP treatment, i.e. research of growth factors of endothelial vessels, autoimmune reaction to S-antigen of the retina and of dosed oxygentherapy etc.

Cryosurgery↗
PubMed2005

The search for the retinoblastoma cell of origin.

The cellular effects of the genetic defects associated with tumorigenesis are context dependent. To better understand the reasons that different cell types require distinct combinations of mutations to form tumours, it is essential to identify and characterize a tumour's 'cell of origin'. Retinoblastoma, a rare childhood cancer of the retina that is caused by RB inactivation, is a good model in which to search for a tumour cell of origin, because retinal development is well understood and the initiating genetic lesion is well characterized. Identifying the cell of origin for this tumour would advance our understanding of how cellular context affects the requirement of specific mutations for cancer initiation and progression.

Animals↗
PubMed1999

Tubby-like protein 1 homozygous splice-site mutation causes early-onset severe retinal degeneration.

PURPOSE: To characterize the disease expression of an autosomal recessive human retinal degeneration associated with a mutation in TULP1 (tubby-like protein 1), a gene with currently unknown function. METHODS: Homozygotes and heterozygotes from an extended Dominican kindred with a TULP1 splice-site gene mutation (IVS14+1,G-->A) were studied clinically and with visual function tests. Sequence analysis of TULP1 was also performed in unrelated patients with severe retinal degeneration from a North American clinic population. RESULTS: Homozygotes had nystagmus, visual acuity of 20/200 or worse, color vision disturbances, bull's eye maculopathy, and peripheral pigmentary retinopathy. Younger patients had a relatively wide extent of kinetic visual fields; older patients had only peripheral islands. No rod function was measurable by psychophysics in any of the patients; markedly reduced cone function was detectable across the visual field of younger patients and in the remaining peripheral islands of older patients. Rod and cone electroretinograms (ERGs) were not detectable using standard methods; microvolt-level cone ERGs were present in some patients. Heterozygotes had normal visual function. No putative pathogenic sequence changes in TULP1 were observed in North American patients with comparably severe retinal phenotypes, mainly in the diagnostic category of Leber congenital amaurosis. CONCLUSIONS: This TULP1 splice-site mutation in homozygotes causes early-onset, severe retinal degeneration involving macular and peripheral cones and rods. The constellation of phenotypic findings suggests that the TULP1 gene product is critically important for normal photoreceptor function and may play a role in retinal development.

Adolescent↗
PubMed1989

The emergence of order in the Drosophila pupal retina.

During pupation, long-range order is imposed on the autonomously developing ommatidia which compose the Drosophila eye. To accomplish this, eight additional cell types arise: the primary, secondary, and tertiary pigment cells, and the four cells that form the bristle. These cells form an interweaving lattice between ommatidia. The lattice is refined when excess cells are removed to bring neighboring ommatidia into register. Recent evidence suggests that in larval development, local contacts direct cell fate. The same appears to be true during pupal development: the contacts a cell makes predict the cell type it will become. Cells which contact the anterior or posterior cone cells in an ommatidium invariably become primary pigment cells. Cells which contact primary pigment cells from different ommatidia become secondary and tertiary pigment cells. Bristle development is in several ways distinct from ommatidial development. The four cells of each bristle group appear to be immediate descendents of a single founder cell. During their early differentiation, they do not make stereotyped contacts with surrounding ommatidial cells, but do make particular contacts within the bristle group. And unlike the surrounding ommatidia, differentiation of the bristles radiates from the center of the eye to the edges. As cells are removed during two stages of programmed cell death, the bristles are brought into their final position. When all cells in the lattice have achieved their final position, a second stage of retinal development begins as structures specific to each cell type are produced. This paper follows these various stages of pupal development, and suggests how local cell-cell contacts may produce the cells needed for a functional retina.

Animals↗
PubMed1996

Cell fate determination in the vertebrate retina.

In the vertebrate central nervous system, the retina has been a useful model for studies of cell fate determination. Recent results from studies conducted in vitro and in vivo suggest a model of retinal development in which both the progenitor cells and the environment change over time. The model is based upon the notion that the mitotic cells within the retina change in their response properties, or "competence", during development. These changes presage the ordered appearance of distinct cell types during development and appear to be necessary for the production of the distinct cell types. As the response properties of the cells change, so too do the environmental signals that the cells encounter. Together, intrinsic properties and extrinsic cues direct the choice of cell fate.

Animals↗
PubMed2007

Rod bipolar cells and horizontal cells form displaced synaptic contacts with rods in the outer nuclear layer of the nob2 retina.

The nob2 mouse carries a null mutation in the Cacna1f gene, which encodes the pore-forming subunit of the L-type calcium channel, Ca(v)1.4. The loss of the electroretinogram b-wave in these mice suggests a severe reduction in transmission between photoreceptors and second-order neurons in the retina and supports a central role for the Ca(v)1.4 calcium channel at photoreceptor ribbon synapses, to which it has been localized. Here we show that the loss of Ca(v)1.4 leads to the aberrant outgrowth of rod bipolar cell dendrites and horizontal cell processes into the outer nuclear layer (ONL) of the nob2 retina and to the formation of ectopic synaptic contacts with rod photoreceptors in the ONL. Ectopic contacts are predominantly between rods and rod bipolar cells, with horizontal cell processes also present at some sites. Ectopic contacts contain apposed pre- and postsynaptic specializations, albeit with malformed synaptic ribbons. Cone photoreceptor terminals do not participate in ectopic contacts in the ONL. During retinal development, ectopic contacts appear in the days after eye opening, appearing progressively farther into the ONL at later postnatal stages. Ectopic contacts develop at the tips of rod bipolar cell dendrites and are less frequently associated with the tips of horizontal cell processes, consistent with the adult phenotype. The relative occurrence of pre- and postsynaptic markers in the ONL during development suggests a mechanism for the formation of ectopic synaptic contacts that is driven by the retraction of rod photoreceptor terminals and neurite outgrowth by rod bipolar cell dendrites.

Animals↗
PubMed1990

Synapsin I expression in the rat retina during postnatal development.

The expression of the synapsin I gene was studied during postnatal development of the rat retina at the mRNA and protein levels. In situ hybridization histochemistry showed that synapsin I mRNA was expressed already in nerve cells in the ganglion cell layer of the neonatal retina, while it appeared in neurons of the inner nuclear layer from postnatal day 4 onward. Maximal expression of synapsin I mRNA was observed at P12 in ganglion cells and in neurons of the inner nuclear layer followed by moderate expression in the adult. At the protein level a shift of synapsin I appearance was observed from cytoplasmic to terminal localization during retinal development by immunohistochemistry. In early stages (P4 and P8), synapsin I was seen in neurons of the ganglion cell layer and in neurons of the developing inner nuclear layer as well as in the developing inner plexiform layer. In the developing outer plexiform layer synapsin I was localized only in horizontal cells and in their processes. Its early appearance at P4 indicated the early maturation of this cell type. A shift and strong increase of labelling to the plexiform layers at P12 indicated the localization of synapsin I in synaptic terminals. The inner plexiform layer exhibited a characteristic stratified pattern. Photoreceptor cells never exhibited synapsin I mRNA or synapsin I protein throughout development.

Animals↗
PubMed2000

Regulation of neurite outgrowth by integrin activation.

During late-embryonic development, retinal neurons lose the ability to attach and extend neurites on the extracellular matrix molecule laminin-1 (LN-1), despite the fact that they retain expression of integrin receptors for LN-1. Here we show that the developmental loss of responsiveness to LN-1 can be reversed by treatments that increase the activation state of integrins. Both extracellular application of Mn(2+) (at micromolar concentrations) and viral-mediated neuronal expression of a constitutively active form of the ras-related GTPase R-ras (R-ras(38V)) potently promoted late-embryonic retinal neurite outgrowth on LN-1 substrata. In both cases, outgrowth was mediated by integrin alpha6beta1 and not alpha3beta1, even though these neurons express alpha3beta1 and use it for outgrowth on other laminin isoforms, as well as on LN-1 that has been proteolytically or conformationally activated (Ivins et al., 1998). Mn(2+)-and to a much lesser extent R-ras(38V)-also reversed the developmental loss of retinal neuron responsiveness to type IV collagen, by promoting the function of integrin alpha1beta1. Interestingly, the responses of other late-embryonic CNS neurons to LN-1 were also enhanced by treatments that activate integrin function, but those of peripheral nervous system neurons (dorsal root ganglion neurons) were either not enhanced (embryonic neurons) or only modestly improved (adult neurons). These results suggest that a developmental decline occurs in the activation state of neuronal integrins, particularly among CNS neurons. Such a decline may underlie some of the intrinsic loss of regenerative ability sustained by CNS neurons during development and may be a valid target for therapeutic intervention.

Animals↗
PubMed1997

Contribution of glial metabolism to neuronal damage caused by partial inhibition of energy metabolism in retina.

Glial cells are relatively resistant to energy impairment, although little is known of the extent to which glial metabolism is affected during partial energy impairment and how this influences neurons. Fluorocitrate has been shown to be a glial specific metabolic inhibitor. Its selective effect on chick retinal Müller cells was verified by measuring incorporation of radiolabel from 3H-acetate and U-14C-glucose into glutamate and glutamine following exposure of isolated embryonic day 15-18 chick retina to 20 microm fluorocitrate. Fluorocitrate significantly reduced the incorporation of radiolabel from acetate and glucose into glutamine, with less effect on incorporation of label from acetate into glutamate and no reduction of label from glucose into glutamate. The relative specific activity (RSA; ratio of glutamine to glutamate) increased between embryonic day 15 and 18 consistent with the increase in glutamine synthetase activity that occurs in Müller cells at this time in chick retinal development. As with previous findings, mild energy stress produced by inhibiting glycolysis with the general inhibitor iodoacetate (IOA) for up to 45 min, caused acute neuronal damage that was predominately NMDA receptor mediated and occurred in the absence of a net efflux of excitatory amino acids. Acute NMDA-mediated toxicity in this preparation is characterized by the selective damage to amacrine and ganglion cells and quantitatively, by GABA release into the medium. When IOA was combined with fluorocitrate, acute toxicity was potentiated and temporally accelerated. Acute damage was first noted at 15 min, occurred throughout all retinal layers and was accompanied by an overflow of excitatory amino acids at 30 and 45 min. Blocking NMDA receptors with MK-801 during IOA plus fluorocitrate exposure attenuated the rise in excitatory amino acids and prevented the swelling in neuronal, but not Müller cells. Following incorporation of radiolabel from acetate and glucose into glutamate and glutamine after different times of exposure to IOA showed that while the effects of incorporation of label from glucose were immediate, glutamine synthesis from acetate was preserved for a longer period of time. These findings suggest that during a partial energy impairment, neuronal metabolism is affected to a greater extent than is glial metabolism. Glial cells may play a protective role in this situation, and can delay the onset of acute neuronal damage.

Animals↗
PubMed2006

Proteomic trajectory mapping of biological transformation: Application to developmental mouse retina.

In this report we introduce a new concept "proteomic trajectory mapping" for the investigation of a complex phenomenon underlying biological transformation and transition. We define proteomic trajectory to be the kinetic trace of protein expression and present a successful proteomic trajectory mapping of complex molecular events underlying postnatal development of mouse retina. Cluster analysis of the trajectory data using a two-state model identified four proteomic trajectory types: two distinct trajectory types accounting for the decline or the rise of protein molecules actively expressed in the juvenile stage (J-type) or in the adult stage (A-type), a class of transient trajectories that mediate the transformation from the juvenile to the adult stage (T-type), and the steady trajectories throughout the entire process of transformation (C-type). The dominance of particular protein categories expressed in each trajectory characterizes the stage of retinal development. Proteomic trajectory mapping will be a powerful tool to study the systematic changes of protein expression caused by physiological, genetic, or pathological agents and the reverse of such changes to the norm by a treatment. The proteomic trajectory mapping is applicable to any biological transformation and, therefore, will be a powerful tool in biomedical sciences.

Animals↗
PubMed1995

High potassium promotes differentiation of retinal neurons but does not favor rod differentiation.

Neural retinal cells of newborn rats were cultured under dissociated culture conditions. Differentiation of several types of retinal cells was confirmed by immunohistochemical detection of type-specific neural phenotypes. We used Thy-1.1 antigen as a ganglion cell marker, HPC-1 or GABA as an amacrine cell marker and rhodopsin as a rod cell marker. With a high concentration of potassium (38 mM), expression of the respective neural phenotypes were differentially affected. High K+ increased the number of Thy-1.1 positive cells 6 to 8 fold, and drastically promoted their neurite extension. The same culture conditions, however, reduced considerably the number of rhodopsin positive cells, possibly due to the unique membrane properties of photoreceptors. A high K+ concentration also promoted differentiation of HPC-1 positive and GABA positive cells, but to a lesser extent than the Thy-1.1 positive cells. Several possibilities were examined to understand the effect of a high K+ concentration on retinal neural cells. The total cell number in cultures with a high K+ concentration was approximately half of that in control cultures at day 3 and slightly smaller at day 11, suggesting that high K+ did not have a positive general effect on the proliferation or survival of retinal cells. Naturally occurring neuronal death (apoptosis) is a well-known phenomenon during retinal development. A histochemical method for detecting DNA fragmentation, a step preceding apoptosis, showed that high K+ had no preventive effect. BrdU (bromodeoxyuridine) immunohistochemistry showed that high K+ did not seem to enhance proliferation of neural precursor cells. These results indicate that a high K+ concentration promotes the expression of neuronal phenotypes but is not a favorable condition for rod differentiation. Since a high K+ concentration is considered to induce depolarization of nerve cells, the present results suggest an anterograde influence from surrounding neuronal cells, through chronic depolarization by elevated K+, is essential for the differentiation and maturation of retinal cells.

Animals↗
PubMed2002

Cellular pattern formation in the retina: retinal regeneration as a model system.

Like many structures in the central nervous system, the neural retina is highly organized at the cellular level. Examples of this cellular organization include the laminar profile of the vertebrate retina, the hexagonal array of ommatidia in the retinas of insects, and non-random two-dimensional patterns of specific vertebrate retinal neurons. These organized cellular ensembles are taxonomically robust, and their importance in visual processing is, although typically not well understood, virtually axiomatic. The presence of non-random cellular patterns in the retina also begs questions concerning the spatial nature of the patterns, and the underlying mechanisms that coordinate their assembly during retinal development and growth. What are the spatial characteristics of the non-random cellular patterns? What molecular signaling schemes might account for their assembly? What are good model systems for investigating these issues? In this review we attempt to provide some preliminary answers to these questions. We present recent advances in our understanding of cellular patterns in the vertebrate retina and the mechanisms that underlie their assembly, the ability of adult anamniote retinas to regenerate following injury, and how these seemingly disparate topics can be successfully merged into an effort to better understand both processes. We combine insights from retinal assembly mechanisms in Drosophila with empirical, quantitative, and theoretical investigations in vertebrates, to propose an inclusive model for retinal cell patterning.

Animals↗
PubMed2004

Approaches to study neurogenesis in the zebrafish retina.

Similar to other vertebrate species, the zebrafish retina is simpler than other regions of the central nervous system (CNS). Relative simplicity, rapid development, and accessibility to genetic analysis make the zebrafish retina an excellent model system for the studies of neurogenesis in the vertebrate CNS. Numerous genetic screens have led to isolation of an impressive collection of mutations affecting the retina and the retinotectal projection in zebrafish. Mutant phenotypes are being studied using a rich variety of markers: antibodies, RNA probes, retrograde and anterograde tracers, as well as transgenic lines. Particularly impressive progress has been made in the characterization of the zebrafish genome. Consequently, positional and candidate cloning of mutant genes are now fairly easy to accomplish in zebrafish. Many mutant genes have, in fact, already been cloned and their analysis has provided important insights into the gene circuitry that regulates retinal neurogenesis. Genetic screens for visual system defects will continue in the future and progressively more sophisticated screening approaches will make it possible to detect a variety of subtle mutant phenotypes in retinal development. The remarkable evolutionary conservation of the vertebrate eye provides the basis for the use of the zebrafish retina as a model of human disorders. Some of the genetic defects of the zebrafish retina indeed resemble human retinopathies. As new techniques are being introduced and improved at a rapid pace, the zebrafish will continue to be an important organism for the studies of the vertebrate visual system.

Alleles↗
PubMed1999

Changing patterns of spatial buffering of glutamate in developing rat retinae are mediated by the Müller cell glutamate transporter GLAST.

The patterns of expression of the glutamate transporter GLAST were compared with the patterns of uptake of exogenous D-aspartate, which is a substrate for all glutamate transporters. At postnatal day 0, fine radial processes and end feet of presumptive Müller cells were weakly immunoreactive for GLAST. At postnatal day 3, intense labelling was associated with astrocytes enveloping newly formed blood vessels on the vitread surface of the retina. Between postnatal days 7 and 10, there was a rapid increase in the intensity of labelling in the Müller cells but clear stratification of GLAST-immunoreactive processes in the inner plexiform layer was not observed until postnatal day 14. By comparison, D-aspartate uptake was initially associated with a wide variety of cellular elements including most neuroblasts, presumptive Müller cells, and astrocytes associated with blood vessels but was absent from the somata of many neurons in the ganglion cell layer and amacrine cell layer. There was a gradual contraction in the numbers of cells that were able to take up D-aspartate, such that, by adulthood, uptake was restricted mainly to Müller cells and astrocytes. We conclude that, during early retinal development, the low levels of GLAST expression by Müller cells permit D-aspartate, and by inference, glutamate, to permeate the retina freely, thus allowing uptake by other glutamate transporters on other cell types. As the retina matures, increased expression of GLAST by Müller cells restricts the access of D-aspartate to other cellular compartments in the retina. This changing pattern of spatial buffering of glutamate by GLAST probably has significant implications regarding our understanding of the role of glutamate during processes such as retinal synaptogenesis.

ATP-Binding Cassette Transporters↗
PubMed1978

Herpes simplex retinitis.

Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infant. Clinically the disease appeared as whitish-yellow punctate lesions, perivascular cuffing, and hemorrhage. The antibody titer to herpes simplex rose from 1:8 on the day of admission to 1:256 on the day of death. Postmortem, intranuclear inclusion bodies that were typical of those found with herpesvirus were seen in the brain and retina. Viral particles consistent with those of herpesvirus were found by electron microscopy in the brain and in the inner-nuclear and ganglion-nerve fiber layers of the retina. This demonstrates the direct infectious nature of herpetic retinitis. Hematogenous spread of the virus to the retina is presumed.

Brain Stem↗