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At least 487 records · Page 27Linked to original sources
PubMed2006

Receptive field structure-function correlates in developing turtle retinal ganglion cells.

Mature retinal ganglion cells (RGCs) have distinct morphologies that often reflect specialized functional properties such as On and Off responses. But the structural correlates of many complex receptive field (RF) properties (e.g. responses to motion) remain to be deciphered. In this study, we have investigated whether motion anisotropies (non-homogeneities) characteristic of embryonic turtle RGCs arise from immature dendritic arborization in these cells. To test this hypothesis, we have looked at structure-function correlates of developing turtle RGCs from Stage 23 (S23) when light responses emerge, until 15 weeks post-hatching (PH). Using whole cell patch clamp recordings, RGCs were labelled with Lucifer Yellow (LY) while recording their responses to moving edges of light. Comparison of RF and dendritic arbor layouts revealed a weak correlation. To obtain a larger structural sample of developing RGCs, we have looked at dendritic morphology in RGCs retrogradely filled with the tracer horseradish peroxidase (HRP) from S22 (when RGCs become spontaneously active, shortly before they become sensitive to light) until two weeks PH. We found that there was intense dendritic growth from S22 onwards, reaching peak proliferation at S25 (a week before hatching), while RGCs are still exhibiting significant motion anisotropies. Based on these observations, we suggest that immature anisotropic RGC RFs must originate from sparse synaptic inputs onto RGCs rather than from the immaturity of their growing dendritic trees.

Action Potentials↗
PubMed1997

Effect of a water-soluble vitamin E analog, trolox C, on retinal vascular development in an animal model of retinopathy of prematurity.

The debate over the efficacy of vitamin E as a therapy for retinopathy of prematurity (ROP) continues 45 years after it was first proposed. The discrepancies between one clinical study and another may be due to the difficulty of delivering a lipid-soluble molecule like vitamin E to the immature retina. Trolox C is a water-soluble analog of vitamin E with potent antioxidant activity. We have studied the effectiveness of intraperitoneal injection of Trolox C in an animal model of ROP. Albino rats were placed in 80% oxygen at birth where they remained for 14 d before sacrifice and assessment of retinal vasculature. Rats were administered 625 microg/kg Trolox C, or vehicle, by intraperitoneal injection on alternate days for the duration of the exposure. Other rats were simultaneously raised in room air, injected, and assessed as controls. Percent avascular retinal area, vascular leakage, and retinal capillary density were measured by computer-assisted image analysis. Trolox C-injected rats had significantly smaller avascular areas (14.6 +/- 4.8% vs. 25.4 +/- 6.3%), less leak area (0.04 +/- 0.07 mm2 vs. 0.16 +/- 0.14 mm2), and greater capillary density (24.3 +/- 2.6 pixel % vs. 18.9 +/- 3.1 pixel %) than vehicle-injected counterparts. These findings indicate that Trolox C facilitated the process of retinal vasculogenesis under hyperoxemic conditions. They also suggest that oxygen free radical-mediated damage plays a role in the pathologic effect of high oxygen rearing of newborn rats. Additional studies are warranted to determine precise site(s) and mechanism(s) of Trolox C activity in this and similar disease models in which peroxidation is believed to play a causal role.

Animals↗
PubMed1999

Patterned expression of BDNF and NT-3 in the retina and anterior segment of the developing mammalian eye.

PURPOSE: The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are hypothesized to play an important role in vertebrate eye development because of their patterned expression in the developing and adult neuroretina, their regulated response to retinal and optic nerve injury, and the effects of altered neurotrophin signaling on retinal development. To further characterize the role of these neurotrophins in mammalian eye development and maintenance, the pattern of expression of BDNF and NT-3 was analyzed in the developing and mature mouse eye. METHODS: Using mouse strains in which the reporter gene lacZ, encoding the enzyme beta-galactosidase, was targeted to either the BDNF or NT-3 locus, the expression of BDNF and NT-3 in the eyes of mice heterozygous for these mutations was analyzed by enzyme histochemistry during embryogenesis, postnatal development, and adulthood. RESULTS: BDNF and NT-3 expression were first observed in the inner and outer segments of the developing optic cup at embryonic days 10.5 to 11.5. As the retina matured, BDNF expression was restricted to retinal ganglion cells and a subset of cells in the inner nuclear layer (INL), whereas NT-3 expression was confined to a small subset of cells in the INL and ganglion cell layer. Both neurotrophins were expressed within the developing retinal pigment epithelium. In the anterior segment, BDNF and NT-3 were expressed at high levels in the developing and mature ciliary epithelium. In the lens and cornea, however, these neurotrophins displayed distinct patterns of expression during development and adulthood. BDNF expression was found in the lens epithelium, immature trabecular meshwork, corneal endothelium, and corneal epithelium, whereas NT-3 expression was confined to the corneal epithelium. CONCLUSIONS: BDNF and NT-3 exhibit different, yet overlapping, patterns of expression during the development and differentiation of the mouse eye. In addition to the neuroretina, the spatiotemporal expression of BDNF and NT-3 may play an important role in the development and maintenance of the lens, ciliary body, trabecular meshwork, and cornea.

Animals↗
PubMed1996

Screening for cytomegalovirus retinitis in children.

OBJECTIVES: To identify immunosuppressed children who are at risk of cytomegalovirus (CMV) retinitis developing and to evaluate the use of laboratory results for identifying this risk. DESIGN: Prospective cohort and retrospective case-control series. SETTING: University hospital pediatric referral center. PATIENTS: Fifty-six consecutive immunocompromised children (ie, the prospective group) with laboratory evidence consistent with acute or recently acquired CMV infection, which was defined as CMV cultured from the blood, urine, nasopharynx, or biopsy specimen, recent seroconversion, a 4-fold increase in the CMV antibody titer, or an antibody titer of 1:512 or greater. Ninety-three immunocompromised children (ie, the retrospective group) with acute CMV or previous CMV exposure, which was defined as a CMV titer of 1:4 or greater and less than 1:512. MAIN OUTCOME MEASURE: Occurrence of CMV retinitis. RESULTS: Cytomegalovirus retinitis developed in 3 children in the prospective group and in 4 children in the retrospective group. The causes of immunosuppression were severe combined immunodeficiency syndrome (n = 2), severe combined immunodeficiency syndrome status post bone marrow transplantation (n = 1), acquired immunodeficiency syndrome (n = 1), and acquired immunodeficiency syndrome status post bone marrow transplantation for leukemia (n = 1), renal transplantation (n = 1), and chemotherapy for leukemia (n = 1). Cytomegalovirus retinitis was associated with a positive CMV culture result from the urine (P = .03) or nasopharynx (P < .001) in the retrospective group. In the retrospective group, one child with congenital CMV infection and CMV retinitis was excluded from analysis because laboratory tests for CMV were not obtained prior to ganciclovir therapy. CONCLUSIONS: Cytomegalovirus retinitis is uncommon in children compared with adults; it occurred in 5% of the children in our series. A screening ophthalmologic examination should be considered in immunocompromised children with positive CMV laboratory results, particularly positive results of urine or nasopharynx cultures.

Adolescent↗
PubMed1996

Retina-derived POU-domain factor-1: a complex POU-domain gene implicated in the development of retinal ganglion and amacrine cells.

A novel POU-domain protein, retina-derived POU-domain factor-1 (RPF-1), has been identified through the isolation of cDNA and genomic DNA clones. In the adult, RPF-1 is expressed only within the CNS, where its expression is restricted to the medical habenulla, to a dispersed population of neurons in the dorsal hypothalamus, and to subsets of ganglion and amacrine cells in the retina. The human RPF-1 gene spans > 125 kb and gives rise to multiple differentially spliced transcripts. In the human retina, the most abundant mRNA isoforms are derived from an alternate splicing event that inserts an evolutionarily conserved peptide of 36 amino acids into the DNA recognition helix of the POU-specific domain. In vitro, the RPF-1 POU domain lacking the insert binds to a consensus Oct-1 binding site, whereas the alternately spliced POU domain does not. RPF-1 protein first appears in the developing mouse retina at e11, where it localizes to neuroblasts that have recently migrated from the mitotic zone to the future ganglion cell layer. These data suggest that RPF-1 is likely to be involved in early steps in the differentiation of amacrine and ganglion cells.

Age Factors↗
PubMed1994

Regulation of ganglioside composition and synthesis is different in developing chick retinal pigment epithelium and neural retina.

We examined the immunocytochemical expression of GM3 and GD3 in 3-day-old chick embryo retinal pigment epithelium (RPE) and neural retina (NR). We also compared the composition of gangliosides and the activities of key ganglioside glycosyltransferases of the RPE and NR of 8-, 12-, and 15-day old embryos. The immunocytochemical studies in 3-day-old embryos showed heavy expression of GM3 and GD3 at the inner and outer layers of the optic vesicle that are the precursors of the RPE and NR, respectively. The compositional and enzymatic studies showed pronounced differences between RPE and NR of 8-day and older embryos. HPTLC showed that at 8 days the major species were GM3 and GD3 in RPE and GD3 and GT3 in NR. As development proceeded, GD3 decreased in both tissues, GM3 became the major ganglioside in RPE, and ganglio-series gangliosides (mainly GD1a) became the major species in NR. At 15 days the major species were GD1a in NR and GM3 in RPE. Enzyme determinations showed that whereas in RPE from 12-day-old embryos GM2 synthase was under the limit of detection and GD3 synthase activity was about sixfold lower than GM3 synthase, in NR the activities of GM3 and GD3 synthases were similar and both six- to ninefold lower than GM2 synthase. These results evidence a markedly different modulation of the ganglioside glycosylating system in cells of a common origin that through distinct differentiation pathways originate two closely related tissues of the optic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Cytoplasmic inclusions within developing mouse retinal photoreceptor cells maintained in culture: possible type A retrovirus particles?

Unusual cytoplasmic inclusions were consistently observed in photoreceptor cells of explants of embryonic mouse retina maintained in culture for 21 days or longer. The inclusions were chiefly spherical (some appeared to be short cylinders) and about 76 nm in diameter. They consisted of a granular/amorphous electron-dense periphery and an electron-lucent core and were usually in clusters, often close to the Golgi apparatus or plasma membrane. They were also commonly present in photoreceptor cell synaptic terminals in the outer plexiform layer. They displayed close relationships with cisterns and tubules of the endoplasmic reticulum and many were located within dilated sacs of reticulum. Narrow, smooth-surfaced tubules appeared to run into or through the cores of some of the inclusion bodies linking them to others. Similar inclusions were not seen in any other cell types in the explants and have not been reported in previous in vivo and in vitro studies of developing or adult mouse retina. The possibility that these inclusions represent Type A retrovirus particles is considered.

Animals↗
PubMed1991

Transcription of a quail gene expressed in embryonic retinal cells is shut off sharply at hatching.

The avian neuroretina (NR) is part of the central nervous system and is composed of photoreceptors, neuronal cells, and Müller (glial) cells. These cells are derived from proliferating neuroectodermal precursors that differentiate after terminal mitosis and become organized in cell strata. Genes that are specifically expressed at the various stages of retinal development are presently unknown. We have isolated a quail (Coturnix coturnix japonica) cDNA clone, named QR1, encoding a 676-amino acid protein whose carboxyl-terminal portion shows significant similarity to those of the extracellular glycoprotein osteonectin/SPARC/BM40 and of the recently described SC1 protein. The QR1 cDNA identifies a mRNA detected in NR but not in other embryonic tissues examined. The levels of this mRNA are markedly reduced when nondividing NR cells are induced to proliferate by the v-src oncogene. QR1 expression in NR is limited to the middle portion of the inner nuclear layer, a localization that essentially corresponds to that of Müller cells. Transcription of QR1 takes place only during the late phase of retinal development and is shut off sharply at hatching. Signals that regulate this unique pattern of expression appear to originate within the NR, since the QR1 mRNA is transcribed in cultured NR cells and is shut off also in vitro at a time coinciding with hatching.

Amino Acid Sequence↗
PubMed1993

Identification and characterization of transcripts present at elevated levels in the undifferentiated chick retina.

Little is known concerning the genes expressed in the neuro-ectodermal cells of the retina, prior to their differentiation into neurons and glia. An analysis of the transcripts present at early stages of retinal development should lead to the identification of functionally important molecules and increase our understanding of the molecular events involved in tissue maturation. Differential screening of a day 3.5 chick retina cDNA library and Northern blot analysis resulted in the discovery of five mRNAs present at elevated levels in the undifferentiated retina. Tissue maturation was accompanied by a decrease in mRNA signal in all five cases and, with the exception of the brain, transcript levels were higher in the immature retina than in the other tissues tested. Two of the cDNAs, corresponding to brain creatine kinase and carbonic anhydrase-II RNAs, had previously been cloned, while the products encoded by the three remaining RNAs were tentatively identified as the chicken counterparts of mammalian cytosolic aldehyde dehydrogenase, stathmin and a member of the fatty acid binding protein family. The elevated levels of these five RNAs in the undifferentiated retina and the subsequent decrease in transcript levels observed upon tissue maturation indicate that the encoded proteins may play important roles in early retinal development.

Amino Acid Sequence↗
PubMed2004

Astrocyte-endothelial cell relationships during human retinal vascular development.

PURPOSE: To evaluate evidence for the presence of vascular precursor cells (angioblasts) and astrocyte precursor cells (APCs) in the developing human retina and determine their relationship. METHODS: Pax-2/GFAP/CD-34 triple-label immunohistochemistry was applied to four retinas aged 12, 14, 16, and 20 weeks of gestation (WG) to label APCs, astrocytes, and patent blood vessels. APCs are Pax-2(+)/GFAP(-), whereas astrocytes are Pax-2(+)/GFAP(+). Adenosine diphosphatase (ADPase) enzyme histochemistry, which identifies endothelial cells and vascular precursors, was applied to human retinas aged 12, 16, 17, and 19 WG. Nissl stain, a nonspecific cell soma marker, was applied to 14.5-, 18-, and 21-WG retinas. Established blood vessels were visualized with CD34 and ADPase. RESULTS: Topographical analysis of the distribution of Nissl-stained spindle cells and ADPase(+) vascular cells showed that these two populations have similar distributions at corresponding ages. ADPase(+) vascular precursor cells preceded the leading edge of patent vessels by more than 1 millimeter. In contrast, Pax-2(+)/GFAP(-) APCs preceded the leading edge of CD34(+) blood vessels by a very small margin, and committed astrocytes (Pax-2(+)/GFAP(+)) were associated with formed vessels and nerve fiber bundles. Two populations of ADPase(+) cells were evident, a spindle-shaped population located superficially and a deeper spherical population. The outer limits of these populations remain static with maturation. CONCLUSIONS: A combination of Pax-2/GFAP/CD34 immunohistochemistry, Nissl staining, and ADPase histochemistry showed that the vascular precursor cells (angioblasts), identified using ADPase and Nissl, represent a population distinct from Pax-2(+)/GFAP(-) APCs in the human retina. These results lead to the conclusion that formation of the initial human retinal vasculature takes place through vasculogenesis from the prior invasion of vascular precursor cells.

Antigens, CD34↗
PubMed2004

Cell death in the developing vertebrate retina.

Programmed cell death occurs naturally, as a physiological process, during the embryonic development of multicellular organisms. In the retina, which belongs to the central nervous system, at least two phases of cell death have been reported to occur during development. An early phase takes place concomitant with the processes of neurogenesis, cell migration and cell differentiation. A later phase affecting mainly neurons occurs when connections are established and synapses are formed, resulting in selective elimination of inappropriate connections. This pattern of cell death in the developing retina is common among different vertebrates. However, the timing and magnitude of retinal cell death varies among species. In addition, a precise regulation of apoptosis during retinal development has been described. Factors such as neurotrophins, among many others, and electrical activity influence the survival of retinal cells during the course of development. In this paper, we present a summary of these different aspects of programmed cell death during retinal development, and examine how these differ among different species.

Animals↗
PubMed2000

Laminin modulates neuritogenesis of developing rat retinal ganglion cells through a protein kinase C-dependent pathway.

Dissociated cells from rat retinae (P2-P21) were cultured to investigate interactions between brain-derived neurotrophic factor (BDNF), various substrates (poly-L-lysine, collagen, and laminin), and protein kinases upon the neuritogenesis of retinal ganglion cells (RGCs). We found that BDNF-promoted neuritogenesis was enhanced by forskolin in RGCs from rats at P2-P21 plated on either poly-L-lysine or collagen. In contrast, in cultures with a laminin substrate, the enhancer effect of forskolin was observed only in RGCs taken from the retina of rats at P2-P6. Laminin blocked the enhancement of BDNF-induced RGCs neuritogenesis by forskolin, in RGCs from either P14 or P21, and induced a tenfold increase of protein kinase C (PKC) activity compared to poly-L-lysine. This blockade was reverted with a selective PKC inhibitor and was reproduced in poly-L-lysine cultures of P14-P21 RGCs with a PKC activator. Because axotomized RGCs need both BDNF and forskolin to regenerate, we suggest that laminin can hinder this effect by simultaneous PKC activation according to a developmentally regulated pattern. We further propose a model of interaction in the optic pathways triggered by BDNF, forskolin, and laminin that may be useful in elucidating some of the biological effects seen with regenerating axons.

Animals↗
PubMed1977

Random segregation of sister chromatids in developing chick retinal cells demonstrated in vivo using the fluorescence plus Giemsa technique.

Experiments were designed to test whether nonrandom segregation of sister chromatids at mitosis has a role in the production of cell diversity during embryogenesis, Segregation was examined in vivo in retinal cells from embryonic chicks. Chromatids were labelled with bromouracil and stained by the fluorescence plus Giemsa technique. No evidence of nonrandom segregation was observed in a frequency distribution of pairs of bifilarly labelled sister chromatids at the third metaphase after the start of labeling. Nor was there evidence that chromatids from homologous chromosomes segregated nonrandomly. Nonrandom segregation is probab;y not a mechanism for cell diversification.

Animals↗