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 325 records · Page 18Linked to original sources
PubMed1980

Ontogeny of the retina and optic nerve in Xenopus laevis. I. Stages in the early development of the retina.

A staging series for retinal histogenesis is described for Xenopus laevis. It is based on scanning EM studies of intact eyes and serial section analysis of silver-stained preparations. Retinal development is arbitrarily divided into twelve stages (I--XII) based on distinct morphological and histological changes. In general, four different phases of retinal development can be identified: an embryonic phase of rapid histogenesis (Nieuwkoop-Faber stages 21--39) and onset of visual function; a second or functional phase completed by stage 52 is a period of growth, synaptogenesis, and the organization of visual function; a third phase ending at metamorphic climax (NF57) when mature function is achieved and binocular vision begins; and a final mature phase at the end of metamorphosis, when road and cones are adult size and the visuotectal projection extends over the entire tectum. Ten of the twelve developmental stages are assigned to the first phase since this is the period of intense morphogenesis and differentiation.

Acetylcholine↗
PubMed2001

Gene expression in the developing mouse retina by EST sequencing and microarray analysis.

Retinal development occurs in mice between embryonic day E11.5 and post-natal day P8 as uncommitted neuroblasts assume retinal cell fates. The genetic pathways regulating retinal development are being identified but little is understood about the global networks that link these pathways together or the complexity of the expressed gene set required to form the retina. At E14.5, the retina contains mostly uncommitted neuroblasts and newly differentiated neurons. Here we report a sequence analysis of an E14.5 retinal cDNA library. To date, we have archived 15 268 ESTs and have annotated 9035, which represent 5288 genes. The fraction of singly occurring ESTs as a function of total EST accrual suggests that the total number of expressed genes in the library could approach 27 000. The 9035 ESTs were categorized by their known or putative functions. Representation of the genes involved in eye development was significantly higher in the retinal clone set compared with the NIA mouse 15K cDNA clone set. Screening with a microarray containing 864 cDNA clones using wild-type and brn-3b (-/-) retinal cDNA probes revealed a potential regulatory linkage between the transcription factor Brn-3b and expression of GAP-43, a protein associated with axon growth. The retinal EST database will be a valuable platform for gene expression profiling and a new source for gene discovery.

Animals↗
PubMedDate not supplied

Normal and pathological mechanisms in retinal vascular development.

Angiogenesis is a complex biologic process that occurs normally in development and in turnover and remodeling of mature vascular networks. Pathological angiogenesis and neovascularization occur in association with retinal and ocular ischemic diseases, in retinopathy of prematurity and other developmental disorders, and in tumor growth and metastasis. We describe current understanding of cellular and molecular mechanisms of retinal vascular development, highlighting aspects that relate to eye diseases, that provide sites of therapeutic intervention in ophthalmology and that are potential avenues for research.

Animals↗
PubMed1994

Immunohistochemical localization of tyrosine hydroxylase, substance P, neuropeptide-Y and leucine-enkephalin in developing human retinal amacrine cells.

Prenatal changes in the neurotransmitter/neuromodulator profiles of tyrosine hydroxylase (for dopamine), substance P, neuropeptide Y, and leucine-enkephalin were studied in developing human retinal amacrine cells by the use of immunohistochemical techniques. Tyrosine hydroxylase was localized between 10 and 12 weeks of gestation, substance P and neuropeptide Y appeared little later around 14 weeks, and leucine-enkephalin-like immunoreactivity was observed at 16 weeks.

Enkephalin, Leucine↗
PubMed1999

Retinal mitosis is regulated by dopa, a melanin precursor that may influence the time at which cells exit the cell cycle: analysis of patterns of cell production in pigmented and albino retinae.

A melanin-associated agent seems to play a role in regulating retinal development. When absent, diverse deficits occur. There is evidence that this agent regulates patterns of mitosis. This study examines retinal development in pigmented and albino rats to identify the regulating agent and its mode of action. Throughout neurogenesis, many more mitotic profiles are found in albinos than pigmented animals. At the peak of retinal neurogenesis, approximately 50% more mitotic profiles are found in albinos than in matched pigmented animals, resulting in abnormal retinal thickening. Concurrently, increasing numbers of pyknotic nuclei are identified, such that later in development retinal thickness normalises. However, the crude centre-to-periphery pattern of cell production is preserved. Abnormal cell proliferation is found in a range of albino rat strains, but it is not present in their brains, confirming that the abnormality is ocular and melanin related. Dopa is a critical element in initial stages of melanin synthesis and is present in abnormally low levels in developing albino retinae. Furthermore, it is an antimitotic agent. Addition of dopa to albino eyes in vitro normalises patterns of cell production. These results are consistent with the hypothesis that dopa is a major regulator of retinal cell production and that it influences the capacity of cells to exit the cell cycle.

Albinism↗
PubMedDate not supplied

Shifting relationships between photoreceptors and pigment epithelial cells in monkey retina: implications for the development of retinal topography.

This study examines the spatiotemporal relationships between retinal pigment epithelium (RPE) and photoreceptors (PR) during development of Macaca nemestrina retina. Our aim was to learn more about the developmental dynamics of these two important cell populations, particularly whether development changes in RPE cell densities mimic those of PR at selected retinal points. Twelve eyes ranging in age from 100 fetal days (Fd) to adulthood were flatmounted; the retinal perimeters were traced; and then sample punches were taken of the RPE and neural retina at the fovea, optic disc, mid- and far-nasal periphery, and far temporal, inferior and superior periphery. The two tissues were gently separated and the RPE cells and photoreceptors from the same region of the punch were counted using Nomarski contrast interference optics. We found that the total number of cones remains stable around 4 million between Fd100 and adulthood, but RPE number increases from 1.6 million at Fd100 to 2.56 million in adulthood. At the fovea, the core:RPE ratio increases from 5.4:1 at Fd100 to 28:1 by adulthood. In the temporal periphery by contrast, the cone:RPE ratio declines from 2.2:1 at Fd100-110 to less than 1:1 in the adult. In the vicinity of the optic disc, the ratio of (cones+rods); RPE remains around 35:1 throughout development, but in the retinal periphery it decreases to the adult value of 22:1. These changing ratios indicate that photoreceptors and RPE cells are redistributed independently during development, and that these two cellular sheets slide over one another to achieve their final distribution. This situation suggests that the forces or factors causing foveation are intrinsic to the neural retina.

Aging↗
PubMed1999

Expression patterns of neurturin and its receptor components in developing and degenerative mouse retina.

PURPOSE: Neurturin (NTN) and its receptor components (GFRalpha2 and Ret) play an important role in the survival of different populations of neurons in the central and peripheral nervous systems. To gain insight into their possible functions throughout normal retinal development and during retinal neuronal apoptosis, the retinal distribution of expression of NTN and GFRalpha2 mRNAs and Ret protein were compared in control and retinal degeneration (rd) mice. METHODS: Eyes from control and rd animals were fixed in paraformaldehyde before sectioning. For in situ hybridization, retinal sections were hybridized with 35S-radiolabeled sense and antisense riboprobes for murine NTN and GFRalpha2 and were autoradiographed. Ret localization was detected by immunofluorescence. RESULTS: Neurturin mRNA expression was modulated through normal postnatal retinal development and was localized primarily to the inner retina and photoreceptor outer segments. GFRalpha2 mRNA displayed a diffuse developmental pattern of expression, but in the mature normal retina, NTN and GFRalpha2 mRNAs were more closely colocalized. Ret protein was localized particularly at the outer segments of photoreceptors, inner retina, and ganglion cell layers, but there were no prominent differences among genotypes. Increased NTN mRNA expression was detected in the retinal pigment epithelium and neural retina in concert with photoreceptor degeneration in rd mouse. In contrast, the level of GFRalpha2 mRNA was lower in rd compared with that in normal retina. CONCLUSIONS: These results suggest that NTN and its receptor are involved in retinal postnatal development and maintenance and that alterations in their transcription patterns are associated with inherited retinal degeneration.

Animals↗
PubMed2005

Transcriptional activity of the paired-like homeodomain proteins CHX10 and VSX1.

CHX10 and VSX1 are homeodomain (HD) proteins essential for normal retinal development. CHX10 is required first for retinal progenitor cell proliferation and later for bipolar cell differentiation, whereas VSX1 is important in the terminal differentiation of a subset of bipolar cells. Elucidating the transcriptional activity of CHX10 and VSX1 is required to understand how these factors control retinal development. We show that CHX10 and Vsx1 can function as transcriptional repressors. When tethered to a promoter by a heterologous LexA DNA-binding domain or its HD, CHX10 repressed multiple classes of activators in different immortalized cell lines. CHX10 blocked TATA-containing and TATA-less promoters, repressed at a distance, and inhibited a complex enhancer positioned upstream or downstream of the reporter gene, whereas retinoblastoma protein (RB) inhibited the downstream enhancer only. Interestingly, CHX10 mildly potentiated a subset of activators in chick neuronal cultures. Thus, CHX10 is both a versatile repressor and a context-specific weak activator. The CHX10 HD and CVC domains were sufficient for DNA binding and repression. VSX1 contains closely related homeo and CVC domains and, like CHX10, also repressed transcription. A VSX1 HD mutation, R166W, that impairs DNA binding and causes keratoconus in humans, hindered repressor function. Therefore, CHX10 and VSX1 may control retinal bipolar cell specification or differentiation by repressing genes required for the development of other cell types.

Animals↗
PubMed1990

Development of retinal vasculature in the cat: processes and mechanisms.

Two principal processes can be distinguished in the development of the retinal circulation in the cat. One process, which forms most of the inner layer of vasculature, involves three stages. First, beginning prior to E (embryonic day) 26, spindle cells of mesenchymal origin spread over the inner surface of the retina. Second, beginning at approximately E48, a network of coarse capillaries forms, apparently derived from spindle cells. Third, major vessels differentiate from the capillary plexus, and the capillaries become thinner and more widely spaced. All three stages begin at the optic disc and spread towards the margin of the retina. The other process involves budding of capillary sized vessels from existing vasculature. This process forms the inner layer of vasculature at the area centralis, the outer layer of vasculature, and the radial peripapillary capillaries. It begins between P (postnatal day) 7 and P10 at the area centralis and spreads to the margins of the retina. The radial peripapillary capillaries form at a later stage (P20). The different topographies of the two processes suggest that they are controlled by distinct mechanisms. In the first process, the formation of vessels follows a pattern set by the early migration of spindle cells. In the second process, the vessels form in a pattern determined by the metabolic needs of the developing retina.

Animals↗
PubMed2003

Management of macular holes that develop after retinal detachment repair.

PURPOSE: To study the characteristics and management of macular holes that develop after prior rhegmatogenous retinal detachment (RD) repair. DESIGN: Retrospective, interventional, consecutive case series. METHODS: The setting was a clinical practice. The case records of all of our patients (n = 12) who developed a new full-thickness macular hole after prior RD repair over an 8-year period were examined. Patients who developed a macular hole after prior RD repair were offered either surgical repair of the macular hole or continued observation. For eyes that underwent macular hole repair, main outcome measures included macular attachment status and postoperative visual acuity. RESULTS: Twelve full-thickness macular holes were detected in a series of 2,380 eyes (0.5% prevalence), which had undergone surgery for prior primary RD. Ten macular holes developed after scleral buckling surgery, two after pneumatic retinopexy, and none were seen after primary vitrectomy. The fovea had been detached in 11 of the 12 eyes at the time of RD. The median time to macular hole diagnosis after RD repair was 3.4 months (range, 0.3-161 months). Eight of the eight eyes (100%) undergoing surgical repair achieved macular reattachment with a median of 3.5 lines of visual improvement at a median of 14.8 months of follow-up. Seven of these eight eyes had an improvement in visual acuity of at least 3 Snellen lines, and four of the eight had at least 20/40 visual acuity postoperatively. Four eyes with macular holes were observed. CONCLUSIONS: Macular holes developed in less than 1% of eyes that had previously undergone repair of rhegmatogenous RD. In our series, these atypical holes were seen predominantly after macula-off detachments, most commonly occurring after scleral buckling procedures. They were effectively repaired using conventional pars plana vitrectomy with long-acting gas tamponade and a variety of adjuvant therapies. A good visual outcome is possible with this approach.

Adult↗
PubMed2001

The EGF receptor and notch signaling pathways control the initiation of the morphogenetic furrow during Drosophila eye development.

The onset of pattern formation in the developing Drosophila retina begins with the initiation of the morphogenetic furrow, the leading edge of a wave of retinal development that transforms a uniform epithelium, the eye imaginal disc into a near crystalline array of ommatidial elements. The initiation of this wave of morphogenesis is under the control of the secreted morphogens Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg). We show that the Epidermal Growth Factor Receptor and Notch signaling cascades are crucial components that are also required to initiate retinal development. We also show that the initiation of the morphogenetic furrow is the sum of two genetically separable processes: (1) the 'birth' of pattern formation at the posterior margin of the eye imaginal disc; and (2) the subsequent 'reincarnation' of retinal development across the epithelium.

Animals↗
PubMed2002

Retinal vascular development is mediated by endothelial filopodia, a preexisting astrocytic template and specific R-cadherin adhesion.

PURPOSE: A neonatal mouse retina developmental model was used to study endothelial cell guidance and subsequent formation of vascular patterns. Since most diseases that cause catastrophic loss of vision do so as a result of abnormal ocular angiogenesis, a better understanding of events regulating normal retinal vascular growth may provide insight into pathologic angiogenesis. METHODS: Development of the retinal vasculature at various postnatal and embryonic time points was analyzed by collagen IV immunohistochemistry and staining with isolectin Griffonia simplicifolia. GFAP-GFP transgenic mice were used to evaluate the relationship between developing vessels and retinal glial cells. Immunolocalization of R-cadherin and intravitreous injection of R-cadherin-specific antibodies was performed to determine the role of R-cadherin during patterning of the superficial and deep retinal vascular plexuses. RESULTS: The characteristic honeycomb pattern of vessel formation observed in the superficial layer is a result of endothelial cell migration over a preexisting astrocytic template. Filopodial extensions associate with underlying astrocytes by protruding from the tips of endothelial cells at the migrating vascular front. Branching of vessels in the primary vascular plexus, as well as appropriate localization of the deep vascular network is mediated by R-cadherin, an adhesion molecule known to be involved in neuronal cell guidance. Injection of antibodies directed against R-cadherin prevents the normally extensive collateralization observed during formation of the superficial network. Injection of anti-R cadherin antibodies also dramatically affects vessels of the deep network. These vessels migrate beyond the normal turning point, penetrating into the deeper photoreceptor layer. CONCLUSIONS: . These studies suggest that angiogenesis and formation of vascular patterns in the retina may use many of the same developmental cues used by neurons in both the central and peripheral nervous systems. Furthermore, retinal vascular endothelial cell guidance mediated by filopodial extensions and neuronal guidance cues may represent a novel conceptual framework within which to study the establishment of vascular patterns in a variety of angiogenic systems.

Animals↗
PubMed1994

A transient expression of alpha B-crystallin in the developing rat retinal pigment epithelium.

PURPOSE: To investigate the expression of alpha B-crystallin in the developing rat retina by immunohistochemical techniques. METHODS: Rat eyes were enucleated on embryonic day 18 and on postnatal days 1, 4, 9, 15, 19, and 90. The avidin-biotin-peroxidase technique was applied to show alpha B-crystallin immunostaining. After the cornea and lens were removed, the developing rat eyeballs were solubilized by 1% sodium dodecyl sulfate. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) were performed to detect alpha B-crystallin in the extracts. RESULTS: From postnatal day 4 to postnatal day 9, alpha B-crystallin was present in retinal pigment epithelium, but it disappeared after postnatal day 15. alpha A-crystallin immunoreactivity was negative in retina and retinal pigment epithelium throughout development. The results of Western blot analysis and ELISA coincided with those of the immunostaining. CONCLUSIONS: These results show that retinal pigment epithelium in mammalian rat retina demonstrates alpha B-crystallin expression in the early developmental stages but loses it after 15 days of age.

Animals↗
PubMed2005

Effect of p75NTR on the regulation of naturally occurring cell death and retinal ganglion cell number in the mouse eye.

Neurotrophins induce neural cell survival and differentiation during retinal development and regeneration through the high-affinity tyrosine kinase (Trk) receptors. On the other hand, nerve growth factor (NGF) binding to the low-affinity neurotrophin receptor p75 (p75(NTR)) might induce programmed cell death (PCD) in the early phase of retinal development. In the present study, we examined the retinal cell types that experience p75(NTR)-induced PCD and identify them to be postmitotic retinal ganglion cells (RGCs). However, retinal morphology, RGC number, and BrdU-positive cell number in p75(NTR) knockout (KO) mouse were normal after embryonic day 15 (E15). In chick retina, migratory RGCs express p75(NTR), whereas layered RGCs express the high-affinity NGF receptor TrkA, which may switch the pro-apoptotic signaling of p75(NTR) into a neurotrophic one. In contrast to the chick model, migratory RGCs express TrkA, while stratified RGCs express p75(NTR) in mouse retina. However, RGC number in TrkA KO mouse was also normal at birth. We next examined the expression of transforming growth factor beta (TGFbeta) receptor, which modulates chick RGC number in combination with p75(NTR), but was absent in mouse RGCs. p75(NTR) and TrkA seem to be involved in the regulation of mouse RGC number in the early phase of retinal development, but the number may be later adjusted by other molecules. These results suggest the different mechanism of RGC number control between mouse and chick retina.

Animals↗
PubMed2006

Ectopic expression of tyrosine hydroxylase in the pigmented epithelium rescues the retinal abnormalities and visual function common in albinos in the absence of melanin.

Albino mammals have profound retinal abnormalities, including photoreceptor deficits and misrouted hemispheric pathways into the brain, demonstrating that melanin or its precursors are required for normal retinal development. Tyrosinase, the primary enzyme in melanin synthesis commonly mutated in albinism, oxidizes l-tyrosine to l-dopaquinone using l-3,4-dihydroxyphenylalanine (L-DOPA) as an intermediate product. L-DOPA is known to signal cell cycle exit during retinal development and plays an important role in the regulation of retinal development. Here, we have mimicked L-DOPA production by ectopically expressing tyrosine hydroxylase in mouse albino retinal pigment epithelium cells. Tyrosine hydroxylase can only oxidize l-tyrosine to L-DOPA without further progression towards melanin. The resulting transgenic animals remain phenotypically albino, but their visual abnormalities are corrected, with normal photoreceptor numbers and hemispheric pathways and improved visual function, assessed by an increase of spatial acuity. Our results demonstrate definitively that only early melanin precursors, L-DOPA or its metabolic derivatives, are vital in the appropriate development of mammalian retinae. They further highlight the value of substituting independent but biochemically related enzymes to overcome developmental abnormalities.

Albinism↗
PubMed1991

The structure of the developing chick retinal pigment epithelium revealed by high resolution scanning electron microscopy.

The retinal pigment epithelium (RPE) in the developing eye of chick embryos has been studied during the early stages of development by high resolution scanning electron microscopy (HRSEM). Specimen preparation techniques which involve removal of the cytoplasmic matrix permitted visualization of organelles and other subcellular structures within RPE cells in detail and in three dimensional (3-D) stereo HRSEM. Using this technique, we were able to examine changes in melanosome structures during development and demonstrate that pigmentation in the RPE was present by day 4 of development. RPE plasma cell membranes showed extensive folding of the apical portion of the membrane closest to the developing neural retina by day 9. Examination of RPE photoreceptor junction revealed photoreceptor inner segments by day 6 and an outer segment by day 9. Mitochondria in the RPE were found to contain tubular cristae only. The ultra-structure in 3-D of the Golgi apparatus, smooth and rough endoplasmic reticulum, lysosomes and nuclear chromatin of the RPE, and Bruch's layer was revealed by the HRSEM method.

Animals↗
PubMed2004

Single cell lineage and regionalization of cell populations during Medaka neurulation.

To study the movement of individual cells and development of cell grouping during neurogenesis, we labeled single cells in early Medaka gastrula at stage 13 [13 hours post-fertilization (hpf)] with a fluorescent vital dye, and analyzed cells and their descendants using time-lapse live recording up to stage 24 (44 hpf). At stage 13, all future neural cells were located in a dorsal 140 degrees sector of the embryo, and migrated toward the vegetal pole; but during stage 15 to 16, they converged towards the midline. Cells that contributed to later neural subdivisions initially formed overlapping populations, but after stage 16+ they formed non-overlapping cell groups having characteristics of tissue 'compartments', preceding development of morphologically distinct neural subdivisions. In early retinal development, a single compartment for future retinal cells was formed superficial to telencephalic and diencephalic compartments, but it was split into left and right eye components at stage 17 in parallel with anterodorsal movement of the diencephalic compartment. At stage 16+, when these compartments were established, Pax6 expression initiated, but only in the laterally located subpopulation of the retina precursor. These observations revise the current view of bilateral retinal development. Continuous live recording of labeled single precursor cells and computer graphics-assisted data analysis, which are presented for the first time in this study, provide excellent means with which to analyze essential cellular processes in organogenesis.

Animals↗
PubMed2001

mosaic eyes: a zebrafish gene required in pigmented epithelium for apical localization of retinal cell division and lamination.

For proper function of the retina, the correct proportions of retinal cell types must be generated, they must be organized into cell-specific laminae, and appropriate synaptic connections must be made. To understand the genetic regulation of retinal development, we have analyzed mutations in the mosaic eyes gene that disrupt retinal lamination, the localization of retinal cell divisions to the retinal pigmented epithelial surface and retinal pigmented epithelial development. Although retinal organization is severely disrupted in mosaic eyes mutants, surprisingly, retinal cell differentiation occurs. The positions of dividing cells and neurons in the brain appear normal in mosaic eyes mutants, suggesting that wild-type mosaic eyes function is specifically required for normal retinal development. We demonstrate that mosaic eyes function is required within the retinal pigmented epithelium, rather than in dividing retinal cells. This analysis reveals an interaction between the retinal pigmented epithelium and the retina that is required for retinal patterning. We suggest that wild-type mosaic eyes function is required for the retinal pigmented epithelium to signal properly to the retina.

Animals↗