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 379 records · Page 21Linked to original sources

Limited topographic specificity in the targeting and branching of mammalian retinal axons.

We have studied in rats the topographic targeting of retinocollicular axons anterogradely labeled by focal retinal injections of the axon tracer DiI. We find that developing retinal axons widely mistarget along both the medial-lateral and the rostral-caudal axes of the superior colliculus (SC). In neonatal rats, labeled axons originating from injection sites in the temporal periphery covering less than 1% of the retina grow over most of the contralateral SC, suggesting that the growth cones of many axons initially fail to recognize their appropriate target region at the rostral SC border. Some of these axons correct their targeting errors and are retained; most do not and are eliminated. In neonates, peripheral nasal axons transiently develop branches throughout the SC. Branches formed by nasal axons are later restricted to a discrete terminal zone at the topographically appropriate, caudal SC border. At the neonatal stage, injections in temporal or nasal retina do result in a zone of increased labeling in the topographically correct region of the SC, but this zone is considerably larger than that labeled by a similar injection at a later stage. Thus, although the early projection is very diffuse, there is some bias for the correct region of the SC. Our findings indicate that in rats, developing retinal axons show only a limited specificity in their topographic targeting and branching. We conclude that mechanisms in addition to directed axon growth are required to establish the order characteristic of mature mammalian retinal projections.

Aging↗

Infiltration of T-lymphocytes in the brain after anterior chamber inoculation of a neurovirulent and neuroinvasive strain of HSV-1.

Following anterior chamber (AC) inoculation of BALB/c mice with the KOS strain of herpes simplex virus type 1 (HSV-1), or with H129, a neuroinvasive and neurovirulent strain of HSV-1, both strains of virus spread from the injected eye through the brain to cause retinitis. However, KOS-infected mice develop retinitis in the uninoculated eye only, whereas H129-infected mice develop bilateral retinitis. Previous studies have shown that infiltrating T-cells in the suprachiasmatic nuclei (SCN) of the hypothalamus of KOS-infected mice concomitant with or before virus protect KOS-infected mice from ipsilateral retinitis. To determine the timing of T cell infiltration and cytokine production in the brain of H129-infected mice, adjacent, frozen sections of the brain were immunostained for virus, T-cells, IL-2, TNF-alpha or IFN-gamma. T-cells infiltrated the brains of H129-infected mice and cytokines were produced in infected tissues. However, virus spread to the optic nerve and retina of both the inoculated and uninoculated eye before T-cells and cytokines were detected in the SCN of H129-infected mice. These results suggest that infiltrating T-cells in the SCN of H129-infected mice may arrive too late to prevent the spread of virus into the optic nerves and retinas and thus prevent development of bilateral retinitis in infected mice.

Animals↗

Effects of GGF/neuregulins on neuronal survival and neurite outgrowth correlate with erbB2/neu expression in developing rat retina.

We have examined the expression of neuregulin and its putative receptors, erbB2/neu, erbB3 and erbB4/tyro2 during retinal development, and tested several potential functions of this class of molecules in dissociated rat retinal cell cultures. At least one form of neuregulin is expressed in the retina, from the earliest stages of retinal development examined; in addition, all three of the known receptors are expressed by retinal neurons in a developmentally regulated manner. When added to cultures of embryonic or neonatal rat retinal cells, neuregulin (rhGGF2) promotes survival and neurite extension from retinal neurons in a dose-dependent manner. These results indicate that in addition to their well described effects on glia, the neuregulins also have direct effects on central nervous system neurons.

Animals↗

Characterization of new transcripts enriched in the mouse retina and identification of candidate retinal disease genes.

PURPOSE: Most retinal disease genes are preferentially expressed in photoreceptors, the light-sensitive cells involved in phototransduction. In addition, some of the genes linked to retinal diseases are essential for normal retinal development. The goal of this study was to identify new transcripts enriched in photoreceptors involved in retinal development or diseases. METHODS: To isolate uncharacterized retinal transcripts, the bioinformatic method Digital Differential Display (DDD) was used. RNA in situ hybridization was used to characterize gene-expression patterns. RESULTS: Twenty-seven mouse ESTs highly represented in retinal libraries were identified. Eight ESTs were predominantly expressed in photoreceptors and/or in the retinal pigment epithelium (RPE), whereas transcripts for other ESTs were detected more ubiquitously in the retinal cells or abundantly in ganglion cells and/or the inner nuclear layer. Mapping of the corresponding human orthologues of the photoreceptor/RPE-enriched genes revealed that two of them are candidate disease genes for retinitis pigmentosa, loci RP22 and RP28. Both of these are predominantly expressed in rod photoreceptors. The candidate RP22 gene codes for a putative transmembrane protein showing homology to Cln8 (ceroid lipofuscinosis, neuronal 8), in which gene mutations are associated with photoreceptors degeneration in mice. Also identified were two genes expressed in photoreceptors that are candidate disease genes for recessive Bardet-Biedl syndrome type 3 (BBS3) and recessive ataxia with RP (AXPC1). CONCLUSIONS: This study demonstrates how bioinformatic analysis can be used to identify novel tissue-specific genes relevant to development and diseases.

Animals↗

Cek5, a tyrosine kinase of the Eph subclass, is activated during neural retina differentiation.

The expression of Cek5, a receptor-type tyrosine kinase of the Eph subclass, and its variant form Cek5+ were examined in the chick neural retina during development. Cek5 is present at high levels at all stages of retinal development examined, while Cek5+ is most abundant during differentiation. Cek5 mRNA expression and immunoreactivity are evenly distributed in the undifferentiated retina. With differentiation, Cek5 becomes concentrated in the inner and outer plexiform layers. While only moderate changes in Cek5 protein expression are observed throughout retinal development, Cek5 phosphorylation on tyrosine in vivo is dramatically increased during differentiation. This suggests that the Cek5 ligand is expressed at high levels and causes Cek5 activation. Thus, Cek5 is likely to play an active role in retinal morphogenesis, particularly during the establishment of interneuronal contacts.

Amino Acid Sequence↗

Indomethacin improves oxygen-induced retinopathy in the mouse.

Retinopathy of prematurity is a disease commonly affecting extremely premature babies. Indomethacin is widely used in the perinatal period. The goal of the present study was to test the hypothesis that indomethacin will improve retinopathy in a mouse model when administered during the period of injury (hyperoxia exposure) to the developing retinal vasculature. C57BL6 mice pups were exposed to 75% oxygen from postnatal d 7 through 12. Indomethacin was administered along with the oxygen exposure as a single subcutaneous dose of 0.5 mg/kg/d for 5 d. Animals were killed on postnatal d 17 through 20. The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein-conjugated dextran-perfused retinal flat mounts and by quantitation of extraretinal nuclei by use of periodic acid-Schiff-stained retinal sections. Animals that received indomethacin during hyperoxia exposure had a significantly lower median (25th, 75th quartile) retinopathy score 5 (4.5, 6) compared with animals that received oxygen [8 (7.5, 10)]. Animals given indomethacin during hyperoxia exposure had a significantly lower extraretinal nuclei count per section (13.3 +/- 4.6) (mean +/- SD) compared with animals that were oxygen exposed (41.9 +/- 14.7). Indomethacin did not affect the normal development of the retinal vasculature or the growth of the animals. The data show that indomethacin improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development or growth of the animals.

Animals↗

Dendritic field development of retinal ganglion cells in the cat following neonatal damage to visual cortex: evidence for cell class specific interactions.

A well-known feature of the mammalian retina is the inverse relation that exists in central and peripheral retina between the density of retinal ganglion cells and their dendritic field sizes. Functionally, this inverse relation is thought to represent a means by which retinal coverage is maintained, despite significant changes in ganglion cell density. While it is generally agreed that the dendritic fields of mature retinal ganglion cells reflect, in part, competitive interactions that occur during development, the issue of whether these interactions are cell class specific remains unclear. In order to examine this question, we used intracellular staining techniques and an in vitro, living retina preparation to compare the soma and dendritic field sizes of alpha and beta ganglion cells from normal retinae with those of cells located in matched areas of retinae in which the density of beta ganglion cells had been reduced selectively by neonatal removal of visual cortex areas 17, 18, and 19. Our intracellular data show that while an early, selective, reduction in beta cell density has little or no effect on the cell body and dendritic field sizes of mature alpha cells, it results in a 13% increase in the mean soma area and an 83% increase in the mean dendritic field area of surviving beta cells. This differential effect suggests that the soma and dendritic field sizes of alpha and beta ganglion cells in the mature cat retina result primarily from competitive interactions during development that are cell class specific.

Animals↗

Neurotrophic stimulation of fetal rat retinal explant neurite outgrowth and cell survival: age-dependent relationships.

Serum-free tissue culture conditions have been defined where stimulation of neurite outgrowth from fetal rat retinal explants occurred only in the presence of an active fraction (BE) prepared from a pig brain extract purification procedure. Under these conditions, 18-20-day fetal retinal explants survived and continued to extend long radial neurites for at least 3 weeks in the presence of BE. However, if fibronectin was not equilibrated onto the basic collagen/poly-L-lysine substrate the neurite outgrowth was restricted to a short halo about the circumference of the explant. In addition, a dose-response relationship was demonstrated in the presence of increasing concentrations of BE with respect to the neurite growth index. The half-maximal response for BE was estimated to be between 5 and 10 micrograms/ml. In addition a number of important age-dependent relationships were observed with respect to BE stimulation of retinal neurite outgrowth and cell survival. An inverse relationship was demonstrated between increased developmental age and responsiveness to BE. After 1 week in culture, there was a 3-fold reduction in retinal neurite length measured from the 2-day neonatal explant when compared to that of the 18-day fetus. There was also a significant inverse relationship demonstrated between the length of time before BE was added to the culture medium and the ability of 20-day fetal explants to extend neurites onto the culture substrate. If BE was added as late as 2 weeks after initial explant culture, the various neurite outgrowth indices were significantly lower than in those situations where BE was added at the time of culture or 1 week later. These results imply that BE not only is required for stimulating neurite outgrowth from fetal rat retinal explants, but may be important in survival and maturation of developing retinal neurons. This hypothesis was confirmed when morphometric analysis was performed on 16- and 20-day explants cultured for a week in the presence or absence of BE. The number of necrotic cells in the developing retinal ganglion plexiform-cell layer of 20-day fetal explants was significantly lower when treated with BE. Conversely, the density of identifiable differentiating retinal ganglion-like cells was significantly greater in response to BE treatment in both 16- and 20-day retinal explants.

Age Factors↗

Development of central retinal vein occlusion in dural carotid-cavernous fistula.

We investigated a 46-year-old woman with central retinal vein occlusion complicating dural carotid-cavernous fistula, resulting in severe loss of visual acuity. Venous stasis retinopathy observed on the first examination progressed severely so that central retinal vein occlusion with retinal neovascularization developed 3 months later. A transvascular embolization discontinuing the feeders from the external carotid artery improved the retinal circulation and the visual acuity. These results indicate that the cause of the progression from venous stasis retinopathy to central retinal vein occlusion is the elevation of pressure in the cavernous sinus.

Arteriovenous Fistula↗

The development of retinal ganglion cells deprived of their targets.

The influence of central targets on the morphological differentiation of retinal ganglion cells was investigated in Xenopus laevis. Since the ganglion cells mature into distinct morphological subtypes after their axons have reached their central targets, it is possible that the target tissues may influence or specify this aspect of neuronal cell development. To test this idea, Xenopus eyebuds were target-deprived by transplantation to the flank region of host embryos where they developed ectopically. The grafted eyes grew at normal rates, but could not make any projections into the central nervous system. To examine the morphological differentiation of the retinal ganglion cells their structures were revealed using an in vitro retinal preparation and intracellular injections of the dye Lucifer yellow. The elaboration and maturation of ganglion cell dendrites were found to be indistinguishable between control and transplanted eyes throughout development. Thus, the development of retinal ganglion cells into distinct morphological classes can occur even when their axons do not interact with the appropriate central targets.

Animals↗

dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina.

Several molecules, such as growth factors and neurotrophic factors, are required both for the differentiation of specific retinal cell types and the long-term cell survival of all retinal neurons. As diffusible factors, these molecules act non-cell-autonomously. Here, we describe the loss of function phenotype for dazed (dzd), a gene that acts cell-autonomously for retinal cell survival and affects the differentiation of rod photoreceptors and the Muller glia. By 3 days after fertilization, dazed mutant embryos have small eyes and slight heart edema. Acridine orange staining indicated a significant degree of retinal cell death occurring by 48 hr after fertilization, and histological analysis revealed that dying cells were found in the inner and outer nuclear layers and near the marginal zones. Although molecular and morphological differentiation of the inner retina and cone photoreceptors occurred, rod photoreceptors failed to differentiate beyond a small patch in the ventral retina and rod precursors failed to respond to exogenously added retinoic acid, which normally potentiated rod differentiation. Mosaic analysis indicated that the dazed gene acts cell-autonomously for rod production and cell survival, as dazed clones failed to produce rods outside the ventral patch and dazed cells were not maintained in wild-type hosts. Raising mutants under constant light resulted in severe retinal degeneration, whereas raising embryos under constant darkness did not provide any additional protection from cell death. Behavioral analysis showed that a subpopulation of adult fish that were heterozygous for the dazed mutation had elevated visual thresholds and were night blind, suggesting that dazed may also be required for long-term dim-light vision. Taken together, our studies suggest a role for the dazed gene in rod and Muller cell development and overall retinal cell survival and maintenance.

Aging↗

Developmental expression of GLUT2 in the rat retina.

We previously demonstrated that GLUT2, a facilitated-diffusion glucose transporter isoform known to play critical roles in the regulation of systemic blood glucose level, is present at the apical ends of Müller cells in the rat retina. As a means of elucidating the ontogeny and possible role(s) of GLUT2 in the developing retina, this study examined its expression at various stages of retinal development by immunofluorescence staining using GLUT2-specific antibody. Evidence of GLUT2 expression first appeared at embryonic day 14 (E14) as linear staining along the boundary between the inner and outer layers of the optic cup, with this staining pattern being present throughout subsequent embryonic and neonatal stages. After the development of photoreceptor cell inner and outer segments (i.e., photoreceptor layer), GLUT2 immunoreactivity was localized along the boundary between the outer nuclear layer and photoreceptor layer. Localization of GLUT2 expression and the timing of its appearance, which coincided with the formation of choriocapillaries, together suggest that GLUT2 is involved in the anterior transport of glucose supplied by choroidal circulation from the early stages of retinal development.

Animals↗

Cell generation, death, and retinal growth in the development of the hamster retinal ganglion cell layer.

During the early postnatal period in the hamster, the retinal ganglion cell layer grows, establishes its central connections, and undergoes substantial cell loss. In this study, we describe the development of the retinal ganglion cell layer with particular attention to the creation of local specializations in cell density. Changes in the number and spatial distribution of cells identified by a single 3H thymidine injection were examined through the period of maximal cell loss (postnatal days 4-10) and at adulthood. The cells of the retinal ganglion cell layer are generated from embryonic day 10 to postnatal day 3. Overall, cell number in the ganglion cell layer increases by approximately 108,000 cells (223%) from postnatal day 1 to 5, because of continued migration of cells generated prenatally. Cell number decreases from postnatal day 5 to 10 (25%), coincident with the presence of degenerating cells. Cell type is correlated with day of generation: the largest cells, all having retinal ganglion cell morphology, are generated on embryonic days 10 and 11; intermediate-sized cells predominantly of ganglion cell morphology on embryonic day 12; and smaller cells of displaced amacrine or glial cell morphology thereafter. At adulthood, the hamster retina shows a streaklike elevation of cell density through central retina. However, at the time of maximal cell number (postnatal day 5), cell density is uniform across the retina. During the period of cell degeneration, cells are lost in greater relative numbers from the retinal periphery. This cell loss occurs principally from the first-generated cells (embryonic days 10 and 11), as shown by both changes in the distribution of labeled cells and by the spatial pattern of labeled degenerating cells. From postnatal day 10 to adulthood, relative cell density continues to decline in the periphery of the retina, thus suggesting that differential growth completes the production of the adult cell density distribution.

Animals↗

Developing rat retinal ganglion cells express the functional NGF receptor p140trkA.

The expression and cellular localization of NGF receptors in the developing rat retina were investigated immunocytochemically and biochemically. In in vitro preparations of retinal neurons from neonatal rats the functional NGF receptor p140trkA was immunocytochemically detected on retrogradely labeled retinal ganglion cells (RGCs). In transverse retinal sections p140trk-immunopositive cells were localized exclusively at the level of the RGC layer. Affinity labeling with 125I-NGF, chemical cross-linking, and immunoprecipitation with anti-NGF antibodies revealed the presence of three complexes which migrate on SDS-PAGE at approximately 90, 95, and 150 kDa. The bands at 90 and 95 kDa correspond to the so-called low affinity NGF receptor p75NGFR. Western blotting experiments using anti-TRK antibodies revealed that the slowest migrating band (150 kDa), which is not immunoprecipitated by monoclonal antibodies to p75NGFR, corresponds to p140trkA. The presence of the functional NGF receptor on RGCs provides the molecular explanation for the reported sensitivity of these cells to the biological action of NGF.

Animals↗

Human retinal ganglion cell development in early prenatal period using carbocyanine dye DiI.

Early development of retinal ganglion cell morphology has been studied in human fetuses of gestational age ranging from 7-8 weeks to 19-20 weeks by retrograde labelling with a lipophilic fluorescent dye, DiI. The retinal ganglion cells with simple and relatively uniform appearance having few dendritic processes between 7 to 11 weeks of gestation show progressive growth and elaboration of dendrites at 17-18 weeks revealing some morphological variation in shapes. It is by 19-20 weeks of gestation that the three major ganglion cell types resembling the alpha, beta and gamma classes of cat ganglion cells are identifiable in the developing human retina. The dendrites of some ganglion cells exhibit varicosities, filiform processes and spines even as early as 10-11 weeks indicating a possibility of involvement in synaptic connectivity.

Animals↗

Presence and further development of retinal dysfunction after 3-year follow up in IDDM patients without angiographically documented vasculopathy.

Abnormalities in neuroretinal function may play a role in the development of diabetic retinopathy. The natural course of diabetic retinal dysfunction in a group of subjects with insulin-dependent diabetes mellitus and with no apparent microvascular alterations in the retina was followed-up with fluorescein angiography and a sensitive electrophysiological technique, i.e., steady-state focal electroretinogram at the macula, for 3 years. Before the beginning and throughout our study, strict glycaemic control was maintained by three or four daily insulin injections under careful monitoring. Analysis of macular electroretinogram provided information from different neural layers. At the first examination, functional activities of postreceptoral neurons were significantly decreased with respect to those of age-matched control subjects. Diabetic patients showed a functional loss of both ganglion cell (0.53 +/- 0.09 vs 0.42 +/- 0.11 microV; t = 5; p = 0.0001) and preganglion cell (0.51 +/- 0.13 vs 0.42 +/- 0.14 microV; t = 2.8; p = 0.007) layers. Diabetes did not alter photoreceptor activity. After 3 years, dysfunction was significantly greater in the preganglion cell layer (0.28 +/- 0.11 microV; t = 6.3; p = 0.0001). Although in some patients further impairment of ganglion cell function was shown, no significant difference was found in 3 years. Photoreceptor function remained unaltered. No vascular abnormalities in the retina were noted after 3 years in this group of patients. Metabolic control was not correlated to functional changes. Our findings suggest that the middle retinal layer is the most sensitive physiological locus of progressive diabetes-induced dysfunction in the absence of angiographically documented abnormalities.

Adolescent↗

Knock-down of GFRalpha4 expression by RNA interference affects the development of retinal cell types in three-dimensional histiotypic retinal spheres.

PURPOSE: To determine the role of glial cell line-derived neurotropic factor family receptor alpha 4 (GFRalpha4) during retinogenesis in a three-dimensional histiotypic in vitro model of the embryonic chicken retina. METHODS: Retinal spheres were cultured from dissociated 6-day-old chicken retina under permanent rotation and transfected with GFRalpha4 siRNA at culture day 2. Alterations on proliferation, apoptosis, and differentiation were determined by semiquantitative RT-PCR, in situ hybridization, and immunohistochemistry after 24, 48, and 72 hours. RESULTS: In contrast to control cultures, retinal spheres transfected with GFRalpha4 siRNA showed reduced GFRalpha4 mRNA expression of only 38% after 24 hours, 3% after 48 hours, and 5% after 72 hours. Based on the suppression of GFRalpha4, a decline in proliferating cells from 10% to 4.8% even after 24 hours and a reduction of sphere size by up to 25% at later culture stages were observed. Moreover, the number of Pax 6-positive amacrine, ganglion, and horizontal cells was significantly decreased from 36% to 16% in GFRalpha4 siRNA-transfected retinal spheres 72 hours after transfection. Additionally, GFRalpha4 gene silencing affected the development of different types of photoreceptors, as revealed by a significant decrease of blue opsin mRNA expression from 29% to 2%, whereas green opsin mRNA and the number rho4D2-positive photoreceptors were significantly increased. CONCLUSIONS: These data showed for the first time that GFRalpha4 plays an essential role in regulating, at least in vitro, the development and differentiation of various cell types during retinogenesis.

Amacrine Cells↗

Notch activity is downregulated just prior to retinal ganglion cell differentiation.

The Notch signaling pathway is important at several stages of retinal development including the differentiation of retinal ganglion cells and Muller glia. The downstream effectors of Notch signaling, Hes1 and Hes5, have been shown to be critical in the retina as well. While Notch activity directly regulates Hes1 and Hes5 elsewhere in the nervous system, it has been unclear whether Hes1 and/or Hes5 are directly regulated by Notch activity in the developing retina. Here, we report that both Hes1 and Hes5 are directly regulated by Notch activity during retinal development. Using fluorescence-based Hes1 and Hes5 reporter constructs, we can monitor Notch activity in progenitor cells in the intact retina, and we find that Notch activity is downregulated just prior to retinal ganglion cell differentiation.

Amino Acid Sequence↗