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PubMed1997

Development of the retinotectal system in the pigeon: a cytoarchitectonic and tracing study with cholera toxin.

The optic tectum of the pigeon (Columba livia) is marked by morphological dorso-ventral and left-right differences. Both features seem to be related to functional specializations, but the responsible developmental mechanisms are unclear. Since the visual system becomes functional only after hatching, the developmental processes might be extended into the post-hatching period. The development of the asymmetries in the tectofugal system, however, depends on an asymmetric light stimulation acting already before hatching. As a first attempt to resolve this discrepancy, we examined the ontogeny of the retinotectal system by labeling the developing retinal projection with cholera toxin subunit B, in conjunction with an analysis of the cytoarchitectonic differentiation of the optic tectum. The data demonstrate that the first fibers to penetrate all retinoreceptive tectal layers could be observed from embryonic day 15 onwards, indicating that visual information could in principle be already processed before hatching. The afferent projection already exhibited the adult lamination pattern directly at the beginning of the invasion of the tectal layers; a surprising finding, since at that time the lamination pattern of the tectal layers did not have an adult appearance. The differentiation of the outer retinoreceptive laminae started only when the whole optic tectum was occupied by retinal fibers, 4 days after hatching, and was finished a week later. The dorso-ventral differences in the thickness of layers 4 and 5 were not apparent before the first week after hatching. The late appearance of these differences indicates that their maturation may be influenced by retinal input.

Age Factors↗
PubMed2006

Multifocal ERG in subjects with a history of retinopathy of prematurity.

PURPOSE: Investigate the function of the central retina in subjects with a history of retinopathy of prematurity (ROP). METHODS: Multifocal electroretinogram (mfERG) responses to a scaled array of 103 hexagons were recorded in subjects, aged 11-23 years (N = 11), with a documented history of mild ROP. The amplitude and implicit time of the components (N(1), P(1), N(2)) of the first order kernel for six concentric rings were compared to those of control subjects (N = 9). RESULTS: The amplitude of each component varied significantly with eccentricity in both ROP and control subjects and was significantly smaller in the ROP subjects. The discrepancy between ROP and control subjects was greatest for central rings (1-3) and smaller for peripheral rings (4-6). The slopes of the functions summarizing log response density as a function of log eccentricity (degrees visual angle) were significantly shallower in ROP subjects. The implicit time of each component was longer in ROP subjects at all eccentricities. CONCLUSIONS: ROP associated alterations in neural retinal development may underlie the subtle macular dysfunction disclosed by the mfERG.

Adolescent↗
PubMed1975

Cytomegalovirus in tears from patients with normal eyes and with acute cytomegalovirus chorioretinitis.

Cytomegalovirus (CMV) was recovered from the tears in eight of 41 (19.5%) children excreting CMV in their urine or saliva. Tear excretors were all immunosuppressed children with acute lymphocytic leukemia. Three had active CMV chorioretinitis and five did not develop retinal disease in nine to 15 months of observation. To our knowledge this was the first report of the recovery of CMV from tears and of acquired CMV chorioretinitis in children. One patient with active chorioretinitis presented with a disciform elevation of the macula. Therapy with adenine arabinoside (ara-A) or idoxuridine was ineffective in two patients while a third patient treated with ara-Apossibly had a more rapid recovery. However, the significance is uncertain due to the unusual disease presentation and lack of data regarding the nature of cytomegalic inclusion disease chorioretinitis. Areas of retinal calcification were present at autopsy in one patient.

Adult↗
PubMed1976

Carbon monoxide retinopathy.

A 26-year-old man who had become comatose after having inhaled carbon monoxide developed retinal venous engorgement and peripillary hemorrhages. Retinal changes closely resembled those that accompany hypoxemia.

Adult↗
PubMed1989

Traumatic wound dehiscence in pseudophakia.

In a series of 11 pseudophakic patients (11 eyes) who sustained wound dehiscence as a result of blunt trauma, five intraocular lenses were dislocated, one was fractured, and two were expulsed. Wound rupture occurred from three days to one year after surgery; the most common cause of injury was a fall. Iris prolapse was observed in all patients, with hyphema observed in seven. Vitreous prolapse occurred in four patients, and three patients developed retinal detachment. Six of the 11 patients had a visual acuity of 20/40 or better after repair. The limbal wound of a pseudophakic eye can dehisce as a consequence of blunt trauma long after surgery, and the position of the intraocular lens can be disrupted. Patients undergoing cataract extraction with intraocular lens implantation should be advised about the importance of long-term protective eyewear.

Aged↗
PubMed1994

Differential distributions of the NMDA receptor channel subunit mRNAs in the mouse retina.

In the retina, the epsilon 2 and zeta 1 subunit mRNAs of the NMDA receptor channel were expressed from embryonic stages and found in ganglion cell layer and whole layer of inner nuclear layer at postnatal day 21 (P21). The epsilon 1 subunit mRNA appeared postnatally and was distributed in ganglion cell layer and an inner third of inner nuclear layer at P21. These findings suggest that molecular organization of the NMDA receptor channel may alter during the retinal development.

Animals↗
PubMed1987

Increased catabolism of VLDL-apolipoprotein B and synthesis of bile acids in a case of hypobetalipoproteinemia.

A 29-year-old man is described who has reduced concentrations of low density lipoprotein (LDL)-cholesterol seemingly due to an unusual variant of hypobetalipoproteinemia. The patient developed retinitis pigmentosa at age 14. When studied at age 28, his total cholesterol was 104 mg/dL, triglycerides 58 mg/dL, LDL-cholesterol 44 mg/dL, and HDL-cholesterol 51 mg/dL. Lipid and lipoprotein levels of his parents and sister were normal. His excretion of bile acids (13.9 mg/kg/d) was markedly elevated at about three times normal, although absorption rates of cholesterol and bile acids appeared to be in the normal range. His high excretion of bile acids equates to a threefold increase in bile acid synthesis. Isotope kinetic studies of his lipoproteins produced unexpected findings. Total production of VLDL-apolipoprotein B (apo B) was estimated to be 20.8 mg/kg/d, which was in the normal range. Synthesis of VLDL-triglycerides was also normal at 12.0 mg/kg/h. However, 75% of VLDL-apo B was removed directly from the circulation, which was much higher than values for direct removal of VLDL-apo B in control subjects. His production rate of LDL-protein (5.2 mg/kg/d) consequently was below normal, although his fractional catabolic rate for LDL (0.40 pools/d) was not distinctly elevated. These data suggest that the patient's hypobetalipoproteinemia was due to increased direct removal of VLDL remnants and not to reduced synthesis of VLDL-apo B; this abnormality may have been the result of enhanced activity of LDL receptors, which in turn was secondary to increased synthesis of bile acids.

Adult↗
PubMed1989

A two-year follow-up study of serum insulinlike growth factor-I in diabetics with retinopathy.

Serum insulinlike growth factor-I (IGF-I) concentration was evaluated prospectively over two years in 35 diabetic patients with severe background or preproliferative retinopathy (group 1) and 24 diabetics with mild background retinopathy matched for age, sex, and glycemic control (group 2). In addition, 12 normal subjects were also studied to assess the variability of individual serum IGF-I levels over two years. Mean serum IGF-I (+/- SD) micrograms/l at entry, one year, and two years was not significantly different in the patient groups (157 +/- 71 v 168 +/- 77; 166 +/- 78 v 159 +/- 87; 143 +/- 58 v 159 +/- 67) or when compared with the normal subjects (181 +/- 47, 188 +/- 30; 221 +/- 56). Eight patients in the preproliferative group and none in the mild background group developed proliferative retinopathy. In this subgroup developing retinal neovascularization, serum IGF-I at the time of the first appearance of retinal new vessels was significantly higher than 3 months (1 to 4 months) before the onset of proliferation (271 +/- 94 v 196 +/- 58; P = .036). Values at the time of proliferation were not, however, significantly different from the mean serum IGF-I value of all patients in group 1 and by 4 months (3 to 6 m) had returned to their previous values. Although a transient elevation of IGF-I occurs at the time of retinal new vessel formation, the rise in serum concentration is not sufficiently great or early enough to be of clinical value as a predictor of retinal neovascularization.

Adult↗
PubMed1987

Visualization of a developing vasculature.

The events involved in vasculogenesis still remain obscure. One difficulty has been the techniques employed to visualize angioblasts, i.e., vascular precursors, during the genesis of blood vessels. The retina provides a unique model for studying these events since it is not completely vascularized in some mammals at birth. Using a previously published magnesium-dependent ATPase technique to visualize the developing retinal vasculature and its precursors, and embedding this tissue in JB-4 methacrylate for serial sectioning, has permitted examination of the retinal vasculogenic processes in dual perspective. The technique has permitted observation of the stages in angioblast differentiation and the apparent importance of glycosaminoglycan-rich cell-free spaces in this process. Perhaps the most important observation is that initial vessel formation occurs by coalescence of angioblasts after differentiation in situ.

Adenosine Triphosphatases↗
PubMed1984

The patterns of expression of two ankyrin isoforms demonstrate distinct steps in the assembly of the membrane skeleton in neuronal morphogenesis.

We have identified in chicken neurons two membrane-bound isoforms of goblin (ankyrin), the specific membrane attachment protein for spectrin in avian erythrocytes, which exhibit distinct patterns of expression and assembly during neuronal morphogenesis. Early in cerebellar and retinal development, neither goblin isoform is detected in mitotic cells. Subsequently, beta-goblin (Mr 237,000) is expressed in postmitotic cells, and gradually accumulates with alpha gamma (brain) spectrin on the neuronal plasma membrane during the phase of cell growth. At the onset of synaptogenesis and the cessation of cell growth, their levels of synthesis decline sharply while the assembled proteins remain as stable membrane components. Concomitantly, there is a dramatic induction in the accumulation of alpha-goblin (erythroid goblin; Mr 260,000) and alpha beta (erythroid) spectrin, whose assembly is limited to the plasma membrane of perikarya and dendrites.

Aging↗
PubMed1984

pp60c-src is developmentally regulated in the neural retina.

We have localized normal cellular pp60c-src in the developing chick neural retina by immunocytochemical staining using antisera raised against bacterially expressed pp60v-src, the src gene product of Rous sarcoma virus. pp60c-src was expressed in developing retinal neurons at the onset of differentiation. Expression of pp60c-src persisted in mature neuronal cells that were postmitotic, fully differentiated, and functional. pp60c-src immunoreactivity was localized within processes and cell bodies of ganglion neurons, processes of rods and cones, and in some but not all neurons of the inner nuclear layer. Protein kinase assays and Western transfer analyses identified the immunoreactive protein as pp60c-src, and confirmed that its expression occurs at the time the first neuronal cells in the retina differentiate. We conclude from these studies that pp60c-src is the product of a developmentally regulated gene that is more important in neuronal differentiation or function than cell proliferation.

Animals↗
PubMed1992

The bride of sevenless and sevenless interaction: internalization of a transmembrane ligand.

During Drosophila retinal development, the R8 photo-receptor neuron induces a neighboring cell to assume an R7 cell fate through cell contact. This is mediated by the transmembrane protein bride of sevenless (boss) on the surface of the R8 cell, which binds the sevenless tyrosine kinase receptor (sev) on the surface of the R7 precursor cell. The boss protein, which contains a large extracellular domain, seven transmembrane segments, and a C-terminal cytoplasmic domain, has an exceptional structure for a ligand of a receptor tyrosine kinase. Using a panel of antibodies directed to various cytoplasmic and extracellular epitopes, we demonstrate that the entire boss protein from its extreme N-terminus to its extreme C-terminus is internalized by sev-expressing tissue culture cells and by the R7 precursor cell in the developing eye imaginal disc. The receptor-mediated transfer of a transmembrane ligand represents a novel mechanism for protein transfer between developing cells.

Animals↗
PubMed1993

The TGF beta homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina.

Development of the Drosophila retina occurs asynchronously; differentiation, its front marked by the morphogenetic furrow, progresses across the eye disc epithelium over a 2 day period. We have investigated the mechanism by which this front advances, and our results suggest that developing retinal cells drive the progression of morphogenesis utilizing the products of the hedgehog (hh) and decapentaplegic (dpp) genes. Analysis of hh and dpp genetic mosaics indicates that the products of these genes act as diffusible signals in this process. Expression of dpp in the morphogenetic furrow is closely correlated with the progression of the furrow under a variety of conditions. We show that hh, synthesized by differentiating cells, induces the expression of dpp, which appears to be a primary mediator of furrow movement.

Animals↗
PubMed1994

Evidence for a tropic role of brain-derived neurotrophic factor in transplanted embryonic retinae.

Developing retinal axons must follow a stereotypic course directing them to the subcortical visual centres which on arrival they must recognise. Transplantation studies suggest that local substrate cues close to the surface of the brainstem and diffusible factors emanating from the target region are important. To test a role for diffusible factors, we transplanted retinae to the cerebral cortex and have shown that outgrowth can be promoted by BDNF secreting fibroblasts.

Animals↗
PubMed1992

Genetics and cytogenetics of retinoblastoma.

Retinoblastoma tumor formation is initiated by loss of function of both alleles at the RB1 locus on chromosome 13. In nonhereditary retinoblastoma (60% of patients), both mutations occur during retinal development. In hereditary retinoblastoma (40% of patients), tumor formation is caused by one germline and one somatic mutation. The RB1 gene encodes a nuclear protein that arrests progression through the G1 phase of the cell cycle. In the absence of intact RB1 protein, unscheduled cell proliferation occurs. Genes on chromosomes 1 and 6, which have not yet been identified, appear to be involved in later stages of tumorigenesis.

Chromosomes, Human, Pair 13↗
PubMed1996

Serum affects the characteristics of excitatory amino acid-binding sites on Müller cells.

The binding of [3H]L-aspartate to membranes obtained from primary cultures of chick retinal Müller cells (glia) was studied Cells seeded in low-serum-containing medium (1%) and maintained in this condition showed an increased number of binding site from 1 to 5 days in vitro (DIV), when compared with controls cultured in medium containing 10% serum; these changes were not reversed by the addition of 10% serum after 48 h in vitro. Increased binding at this age was due to the expression of a low affinity binding system, competitively inhibited by the glutamate uptake blocker L-aspartate-beta-hydroxamate, suggesting that high serum might inhibit the expression of uptake sites at precise maturation stages. Experiments showed the effect was due to a thermolabile serum component. The increase in binding sites is parallel in time to both an increase in aspartate uptake and the initiation of synaptogenesis in the whole retina. Our results suggest that the presence of serum at defined stages in retinal development, could result in the elevation of extracellular glutamate and the concomitant excitotoxic death of neuronal cells, due to a decreased glutamate uptake by glial cells.

Animals↗
PubMed1993

Early opsin expression in Xenopus embryos precedes photoreceptor differentiation.

The visual pigment which serves as the first step in the phototransduction cycle in vertebrate rod cells consists of a retinal chromophore which is linked to the transmembrane protein, opsin. Opsin genes have been isolated from a number of different organisms and studies have shown opsin to be developmentally regulated with both mRNA and protein expression associated with the morphological differentiation of photoreceptor cells. Due to its potential utility as a marker for rod photoreceptor determination in studies of retinal tissue interactions, and because no amphibian opsin genes have as yet been cloned, we isolated cDNA clones of the Xenopus laevis opsin gene. Sequence analysis shows that within the coding region Xenopus opsin shares a high degree of identity with other rod opsin genes, except at the C-terminal where it more closely resembles the mammalian color opsins. A developmental analysis, on the other hand, reveals that Xenopus opsin transcripts are detectable in a retina-specific fashion early in retinal development. Using in situ hybridization we find that Xenopus opsin mRNA is initially restricted to a few isolated cells in the presumptive photoreceptor layer which express the gene at relatively high levels. This suggests that rod photoreceptor determination occurs in single cells, and that the mechanisms controlling opsin expression in Xenopus are initiated well before any evidence of morphological differentiation.

Amino Acid Sequence↗
PubMed1992

Development of gamma-aminobutyric acid-immunoreactive neurons in normal and intracranially transplanted retinas in rats.

Retinas from embryonic day 14 Sprague-Dawley rats were transplanted intracranially to the midbrain or cortex of newborn (P0) rats with right eyes enucleated at the time of transplantation and the gamma-aminobutyric acid (GABA) immunoreactivity in developing retinal transplants, host as well as normal retinas, was studied. The results showed that GABA-immunoreactive neurons were identified in retinas of normal and host rats from the day of birth (P0) onward and that their somata were distributed primarily in the inner half of the internal nuclear layer and in the ganglion cell layer. The adult pattern of GABA immunoreactivity was first observed at P16 when several immunoreactive sublaminae were clearly identifiable in the inner plexiform layer. In contrast, gamma-aminobutyric acid-immunoreactive somata could not be identified in retinal transplants until P4, with a significant reduction in the density and number of GABAergic neurons detected by P12. Moreover, only two immunoreactive sublaminae were observed in the inner plexiform layer in all transplants at P12, as well as in more mature stages. These results suggest that significant changes occurred in the GABA system of the transplanted retina, despite the fact that the overall pattern of organization of the GABAergic neurons and their processes in the retinal transplants was comparable to that of the normal retina.

Animals↗