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At least 937 records · Page 52Linked to original sources
PubMed2002

Transforming growth factor-beta induced cell death in the developing chick retina is mediated via activation of c-jun N-terminal kinase and downregulation of the anti-apoptotic protein Bcl-X(L).

Cell death in general and especially in neuronal cells is regulated by a complex interplay between survival and death signals, generated by extracellular factors like neurotrophins and intracellular regulation mechanisms. The pleiotrophic transforming growth factor beta (TGF-beta) influences life and death decisions in cells depending on cell type and other growth factors present. It has been previously shown that TGF-beta is necessary to induce ontogenetic cell death during retinal development. In the present study, we analyzed the underlying intracellular signaling processes involved in TGF-beta mediated cell death. We established a cell culture system mimicking the situation of ontogenetic cell death in vivo with cultured retinal cells isolated from the retinae of embryonic day 7 white leghorn chick embryos. The neutralization of TGF-beta inhibits cell death of cultured retinal cells whereas exogenous application of TGF-beta is followed by enhanced apoptosis as observed by in situ cell death detection (terminal deoxynucleotidyl transferase-mediated nick end labeling) assay. TGF-beta induces the activation of c-jun N-terminal kinase in the mitogen-activated protein kinase (MAP kinase) pathway and provokes downregulation of the anti-apoptotic BCL-X(L) protein. Thus, TGF-beta influences cell death via activation of a pro-apoptotic MAP-kinase cascade accompanied by a downregulation of anti-apoptotic signals.

Animals↗
PubMed2002

In vitro isolation and expansion of human retinal progenitor cells.

Human retinal development proceeds with temporal and spatial precision. Although differentiation starts around the beginning of the third month of gestation, the majority of cells in the outer neuroblastic layer of human neural retina are still proliferating, as evidenced by their Ki-67 immunoreactivity. In the present study, the proliferating human retinal progenitor cells (HRPCs) were isolated and expanded in culture. They were capable of dividing for multiple generations (with passage 8, the latest tested) and differentiating to several retinal cell phenotypes. These findings indicate that human retina at the 10th-13th week of gestation harbors progenitor cells that can be maintained and expanded in vitro for multiple generations. The availability of such cells may have important implications with respect to human degenerative retinal diseases, as these HRPCs have the potential to be used therapeutically to replace damaged retinal neurons.

Cell Culture Techniques↗
PubMed1999

Requirement for the zebrafish mid-hindbrain boundary in midbrain polarisation, mapping and confinement of the retinotectal projection.

The organizer at the midbrain-hindbrain boundary (MHB organizer) has been proposed to induce and polarize the midbrain during development. We investigate the requirement for the MHB organizer in acerebellar mutants, which lack a MHB and cerebellum, but retain a tectum, and are mutant for fgf8, a candidate inducer and polarizer. We examine the retinotectal projection in the mutants to assay polarity in the tectum. In mutant tecta, retinal ganglion cell (RGC) axons form overlapping termination fields, especially in the ventral tectum, and along both the anterior-posterior and dorsal-ventral axis of the tectum, consistent with a MHB requirement in generating midbrain polarity. However, polarity is not completely lost in the mutant tecta, in spite of the absence of the MHB. Moreover, graded expression of the ephrin family ligand Ephrin-A5b is eliminated, whereas Ephrin-A2 and Ephrin-A5a expression is leveled in acerebellar mutant tecta, showing that ephrins are differentially affected by the absence of the MHB. Some RGC axons overshoot beyond the mutant tectum, suggesting that the MHB also serves a barrier function for axonal growth. By transplanting whole eye primordia, we show that mapping defects and overshooting largely, but not exclusively, depend on tectal, but not retinal genotype, and thus demonstrate an independent function for Fgf8 in retinal development. The MHB organizer, possibly via Fgf8 itself, is thus required for midbrain polarisation and for restricting axonal growth, but other cell populations may also influence midbrain polarity.

Animals↗
PubMed2003

Isolation of the mouse nyctalopin gene nyx and expression studies in mouse and rat retina.

PURPOSE: It has been shown recently that mutations in NYX (nyctalopin on chromosome X), encoding a novel protein associated with the leucine-rich repeat (LRR) protein superfamily, are responsible for the complete form of X-linked congenital stationary night blindness (CSNB1). This study describes the isolation and molecular characterization of the mouse orthologue Nyx and its expression pattern in the retina. METHODS: Nyx was isolated by conventional DNA library screening and polymerase chain reaction (PCR)-based approaches. Gene expression in different mouse tissues was studied by RT-PCR. Subsequently, the expression pattern of Nyx and its gene product in mouse and rat retinas was investigated by RNA in situ hybridization and immunohistochemistry with Nyx-specific antibodies. RESULTS: The Nyx gene encodes a protein of 476 amino acids that contain 11 consecutive LRR motifs flanked by amino- and carboxyl-terminal cysteine-rich LRRs. At the amino acid level, Nyx is highly homologous to its human orthologue (86% identity). The gene is expressed in the eye but also, at lower levels, in brain, lung, spleen, and testis. Nyx expression was found during all stages of postnatal retinal development and was confined to cells of the inner nuclear layer and the ganglion cell layer in adult mouse and rat retinas. CONCLUSIONS: These data suggest an important function of the Nyx protein in the inner retina and provide evidence that CSNB1 is based on a defect in the inner retinal circuitry.

Amino Acid Sequence↗
PubMed1990

A burst of differentiation in the outer posterior retina of the eleven-week human fetus: an ultrastructural study.

Many studies on human retinal development have cited the third gestational month as a period when the posterior retina undergoes rapid differentiation and maturation, including a lining up of cone precursors. Ultrastructural data on the posterior retina during the third month are very limited, and totally lacking for the cone monolayer. We have examined two human fetal retinas between ten and 11 gestational weeks. Before the appearance of the cone monolayer, the outer neural retina consists of a homogeneous population of undifferentiated neuroblasts. Mitotic figures are still evident, even posteriorally. There is no outer plexiform layer (OPL). The interface of neural retina to retinal pigment epithelium (RPE) is largely featureless. By 11 weeks, the posterior retina has a thin OPL that separates the many rows of cells in the developing inner nuclear layer from the single tier of macular cone precursors. The RPE monolayer consists of cuboidal cells whose apical surface elaborates ridges of cytoplasm and branched processes that project into the subretinal space. The large, cuboidal cones are linked to each other and Müller cells at the outer limiting membrane. They show definitive signs of the structural polarity typical of vertebrate photoreceptors. Their apical cytoplasm contains many organelles common to the inner segment, while the basal cytoplasm has synaptic ribbons and vesicles, and receives invaginating contacts from processes in the OPL neuropil arising from differentiating second-order neurons. Lateral cone surfaces are mutually underlain by large subsurface cisterns.

Cell Differentiation↗
PubMed1992

Nonintegrin laminin receptors in the nervous system: evidence for lack of a relationship to P40.

Laminins are extracellular matrix proteins that mediate their effects on cells through integrin and nonintegrin receptors. Two receptors of 67 and 110 kD that bind laminin with a high affinity (Kd approximately nM) have been reported in neural cells. Here, we discuss these and other nonintegrin laminin receptors that have been implicated in neural function. In addition, we report studies characterizing a 43 kD protein, (P40), immunologically related to the 67 kD laminin receptor, which may be involved in retinal development. In our studies, polyclonal antisera (anti-P-20-A) to a synthetic peptide derived from the sequence of a cDNA for a putative high-affinity laminin receptor (67 kD) detected a protein of 43 kD in immunoblots of adult rat retinas. Immunohistochemistry with this antiserum showed that the retinal immunoreactivity was predominantly localized in the ganglion cell layer of both adult chicken and rat retinas where it appeared to be intracellular. Retinal ganglion cells were shown to be immunoreactive by retrogradely labeling them from the superior colliculus with a lipophilic dye and subsequently with anti-P-20-A antisera. Consistent with the preferential localization of the P-20-A immunoreactivity in ganglion cells, there was a substantial decrease in the amounts of P40 on Western blots following optic nerve section and resulting retinal ganglion cell death. Screening of a rat (PC12 cell) cDNA library with the anti-P-20-A antiserum further confirmed the specificity of the antiserum for the rat homologue of P40. Rat P40 is 97% identical to the mouse and 87% identical to human P40 at the nucleic acid level and 98% at the protein level. Restriction mapping of the rather abundant positive clones in the library that cross-hybridized with a human cDNA probe for P40 indicated that the full-length cDNA of 1.2 kb was the major and perhaps the only cDNA in the library. In Northern blots of adult rat retina, these clones hybridized to a single 1.2-kb transcript. Electroblots of retinal homogenates probed with radioiodinated laminin demonstrated binding to a broad band at 110 kD, but none at 43 kD. Taken together these findings suggest that P40 may not be a laminin receptor and are in keeping with the hydrophilic composition of the protein, its intracellular localization, as well as other features predicted by its nucleic acid sequence.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1990

[Clinical features and prognosis of retinal lattice degeneration].

110 cases (110 eyes) of retinal lattice degeneration were clinically observed and followed up for 3-8 years. Most lesions were located in the superotemporal quadrant, band-shaped, and parallel to the ora serrata. 80.9% of the lesions presented various degrees of pigmentation, 67.1% yellowish white spots, and 83.6% white lines. 32.9% of the eyes developed retinal holes. Most lattice degenerations were accompanied by vitreous degeneration and vitreoretinal traction. The disease progressed only slowly, though in a few cases it tended to expand.

Adolescent↗
PubMed1980

Progressive retinal atrophy in the Samoyed.

In Samoyeds 2-5 years old, progressive retinal atrophy was evidenced ophthalmoscopically by peripheral tapetal hyperreflectivity and vascular attenuation, with marked generalized retinal thinning and vascular attenuation at 5-8 years. Pupil response remained active until late in the disease. Histologically, early retinal development was normal, with lesion onset paralleling that of ERG abnormalities. Pedigree examination and test-breeding results were compatible with simple autosomal recessive inheritance.

Animals↗
PubMed1997

[The incidence of retinal detachment after extracapsular cataract extraction in high myopia].

PURPOSE: A retrospective study was performed to determine the incidence of retinal detachment after extracapsular cataract extraction in high myopia and the risk factors associated with the occurrence of retinal detachment. METHODS: Of the 463 patients (463 eyes) who had undergone extracapsular cataract extraction with or without intraocular lenses implant between July 1993 and January 1994, 90 patients companied with high myopia and the others were senior cataract. All patients had been followed up for 27 to 33 months. RESULTS: One (1.11%) developed retinal detachment in the patients with high myopia, and no retinal detachment occurred in the patients with senior cataract. The difference of the incidence of retinal detachment between two groups were no significant (P > 0.05), More myopic patients underwent Nd:YAG laser capsulotomy (P < 0.05). CONCLUSION: Comparing with intracapsular method, extracapsular cataract extraction decreased the risk of retinal detachment even in the high myopic patients. The risk factors for retinal detachment were young patients, long eye axis and posterior capsulotomy.

Aged↗
PubMed2002

Transmitter-evoked local calcium release stabilizes developing dendrites.

In the central nervous system, dendritic arborizations of neurons undergo dynamic structural remodelling during development. Processes are elaborated, maintained or eliminated to attain the adult pattern of synaptic connections. Although neuronal activity influences this remodelling, it is not known how activity exerts its effects. Here we show that neurotransmission-evoked calcium (Ca(2+)) release from intracellular stores stabilizes dendrites during the period of synapse formation. Using a ballistic labelling method to load cells with Ca(2+) indicator dyes, we simultaneously monitored dendritic activity and structure in the intact retina. Two distinct patterns of spontaneous Ca(2+) increases occurred in developing retinal ganglion cells--global increases throughout the arborization, and local 'flashes' of activity restricted to small dendritic segments. Blockade of local, but not global, activity caused rapid retraction of dendrites. This retraction was prevented locally by focal uncaging of caged Ca(2+) that triggered Ca(2+) release from internal stores. Thus, local Ca(2+) release is a mechanism by which afferent activity can selectively and differentially regulate dendritic structure across the developing arborization.

Acetylcholine↗
PubMed1989

Optic nerve sectioning does not affect the development of the retina.

The development of the retina of the albino rat was studied after sectioning of the optic nerves on the 2nd postnatal day. The 2nd day represents a stage at which the retina shows only the ganglion cell layer clearly delineated from an undifferentiated mass. Section of optic nerves at this stage did not affect the subsequent retinal development. Both control and experimental eyes developed at the same pace. Some minor degrees of 'retardation' e.g. the sizes of outer segments, appeared to deviate in the experimental retinae.

Animals↗
PubMed2003

Expression of photoreceptor-associated molecules during human fetal eye development.

PURPOSE: A characteristic feature of the human retina is the early differentiation of foveal cells followed by a central to peripheral wave of maturation. This can obscure the true onset of differentiation when regions other that the fovea are sampled, or when methods based on whole retina or whole eye tissue are employed, such as reverse transcription-polymerase chain technique (RT-PCR). In order to assess the suitability of RT-PCR based approaches during human retinal development and to gain insight into the developmental progression of photoreceptor differentiation and maturation in the human, we analyzed the expression of several photoreceptor-associated genes by immunocytochemical labeling (ICC) of the foveal region as well as by RT-PCR of total RNA from whole fetal eyes from different developmental stages. METHODS: Expression of phosphodiesterase beta (PDEB), interphotoreceptor binding protein (IRBP), tubby-like protein (TULP), short wavelength specific (S) opsin, long and medium wavelength specific (L/M) opsin, rod opsin and the transcription factors Crx and Nrl were assessed by RT-PCR from total RNA prepared from snap frozen intact human fetal eyes ranging from fetal week 9 (Fwk 9) to Fwk 18. ICC labeling was performed in a large number of eyes within an age group for IRBP, TULP, Nrl, S opsin, L/M opsin and rod opsin on frozen sections that included the fovea centralis. RESULTS: All ICC markers appeared first in or around the fovea. We detected PDEB and Crx expression as early as Fwk 10, by RT-PCR. TULP and IRBP were first observed with ICC in a small number of foveal cones at Fwk 9, although the first transcripts were not detected until Fwk 12. Nrl-positive nuclei appeared around the fovea by Fwk 11 and S opsin-positive cones by Fwk 12. L/M opsin-positive cones and rod opsin-positive rods were first detected between Fwk 15-16. In general, ICC labeling in the fovea was present for most genes up to 2 weeks before the corresponding transcripts could be successfully amplified by RT-PCR from whole eye tissue. CONCLUSIONS: Our results indicate that in order to pinpoint exactly when and where a molecule appears, ICC labeling of the fovea is a more reliable indicator. RT-PCR was prone to underestimate the exact onset of expression of the molecules tested, yet it faithfully recapitulated the sequence in which they appeared. In addition, our data show that in the human fetal retina, Crx and Nrl are both expressed when the first rod photoreceptors are being generated. This agrees well with previous in vitro results suggesting a synergistic action of both proteins during differentiation of human rod photoreceptors.

Biomarkers↗
PubMed2006

Unique vascular phenotypes following over-expression of individual VEGFA isoforms from the developing lens.

Formation of a correctly organised vasculature and subsequently embryonic survival is critically dependent on the dosage and site-specific expression of VEGF. Murine VEGF exists in three common isoforms (viz. 120, 164 and 188 amino acids) having different organ specific distribution levels. Gene knock-in studies show that expression of any of the individual isoforms of VEGF extends survival until birth, although each is associated with distinct organ-specific abnormalities. Comparison of the effects of VEGF isoform expression is complicated by the general lethality of mis-expression, in addition to cumulative effects of adjacent tissues from the inappropriately patterned vasculature. Here we investigate the effects of over-expression of individual VEGFA isoforms from the lens-specific alphaA-Crystallin promoter and characterise their effects on the vessel morphology of the hyaloid and developing retinal vasculature. Since the hyaloid vasculature is an anatomically distinct, transient vasculature of the eye, comprising 3 cell types (endothelium, pericytes and macrophages) it is possible to more readily interpret the role of individual VEGF-A isoforms in vascular pattern formation in this model. The severity of the vascular phenotype, characterised by a hyperplastic hyaloid at E13.5 and subsequently retinal vascular patterning and ocular defects, is most severe in transgenics over-expressing the more diffusible forms of VEGFA (120 and 164), whereas in VEGFA(188) transgenics the hyaloid vascular defects partially resolve post-natally. The results of this study indicate that individual isoforms of VEGFA induce distinct vascular phenotypes in the eye during embryonic development and that their relative doses provide instructive cues for vascular patterning.

Animals↗
PubMed1997

Levels of dopamine and noradrenaline in the developing of retina--effect of light deprivation.

The effect of light deprivation on the levels of dopamine and noradrenaline was studied in the developing rat retina. These transmitters were estimated in three groups of rats: (i) cycling light reared; (ii) dark reared since birth; and (iii) dark reared since birth, but exposed to cycling light for 1 day prior to the estimation of catecholamines. Our results show that (1) there is a progressive decrease in the levels of dopamine and noradrenaline in the cycling light and dark reared rats during postnatal development; (2) dark rearing further reduces the content of dopamine and noradrenaline; and (3) restoration of physiological (light) stimulus in the dark-reared rats during the early postnatal period results in the recovery of noradrenaline to a greater extent than that of dopamine. This study demonstrates a progressive decrease in the plasticity of dopaminergic system during retinal development, while such a decrease is not apparent in the noradrenergic system.

Animals↗
PubMed1992

Developmental potential.

In summary (and probably to no one's genuine surprise), it seems clear that some of the key themes in the mechanisms employed during development reiterate themselves throughout the animal kingdom. Yet, as our understanding becomes more refined, new and beguiling observations point to unique aspects of each developmental program. The concentration and absolute position of a variety of positional signaling molecules is likely to be very important in determinative events (establishment of the anteroposterior positioning in a field as in retinal development, establishment or enactment of a hox code, and selector gene regulation through gradients in Drosophila). Appropriate signalling responses are virtually certain to depend critically on the appropriate expression of each component of cellular signal transduction pathways (initiated by the activation of cell-surface receptor protein kinases to finally eliciting gene expression changes through the differential activity of specific transcription factors). The important biochemical details of transcription factor activation of specific respondent genes may be either simpler (as indicated from the murine/Drosophila domain swap experiments) or more complicated (from the responses of mim-1 to cellular versus viral myb proteins) than we had heretofore anticipated.

Animals↗
PubMed1984

Transplantation of tectal tissue in rats. IV. Maturation of transplants and development of host retinal projection.

We have examined the time course of maturation of embryonic tectal tissue transplanted to the midbrain region of newborn rats and studied the development of the host retinal projection to the grafts. Transplants were examined 2-19 days after transplantation. The morphology of developing transplants was studied using Holmes silver and neutral red stained material. Tectal transplants attained their mature morphology about 17 days after transplantation. The time course of tectal transplant maturation appeared to be similar to that of normal superior colliculus in situ. The development of the host retinal projection into the transplants was examined by injecting the host eyes with horseradish peroxidase (HRP) at various times after transplantation. Retinal fibers anterogradely labeled with HRP were first seen growing into the transplants 3-4 days after transplantation. Ingrowing fibers were always located close to the surface of the transplants. The rate of growth of optic axons into the grafts was estimated to be about 250 to 300 micron per day. Patch-like arborizations of retinal afferents were formed soon after innervation and the mature pattern of optic innervation was established by about two weeks. There was no evidence for an initial transitory phase in which the axons invaded the whole transplant. The development of the host retinal projection preceded morphological maturation of the transplants. The mode of ingrowth of retinal axons into tectal grafts was in many respects similar to the way optic fibers grow into the superior colliculus during normal in situ development. The transplant technique thus provides an opportunity to manipulate and analyze the factors which guide optic fiber growth in intact brains.

Animals↗
PubMed1994

Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53.

A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen-transforming activity is attributable, at least in part, to the inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins, we addressed the role of p53 in the development of retinoblastoma in mice. Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact. Rather than developing retinoblastomas, the retinas of these mice degenerate due to photoreceptor cell death at a time in development when photoreceptors are normally undergoing terminal differentiation. The dying cells exhibit the histological and ultrastructural features of apoptosis and contain fragmented DNA. p53 is required for the induction of apoptosis in this model, because mice expressing E7 in a p53 nullizygous background develop retinal tumors instead of undergoing retinal degeneration.

Animals↗
PubMed1986

Extended retinal tamponade in the treatment of retinal detachment with proliferative vitreoretinopathy.

We have used intraocular sulphur hexafluoride or liquid silicone as an adjunct to vitreous surgery in the treatment of a non-randomised sequential series of 19 eyes with retinal detachment complicated by proliferative vitreoretinopathy. We have studied the surgical results and complications of these two tamponades and drawn preliminary conclusions on their use in retinal reattachment surgery. After a seven-month minimum follow-up 13 (68%) of the eyes have reattached retinas. Six (60%) of 10 eyes treated only with silicone have reattached retinas, and four (67%) of six eyes treated only with sulphur hexafluoride gas tamponade have reattached retinas. An additional three eyes treated initially with silicone oil subsequently developed retinal detachments; all were successfully reattached with sulphur hexafluoride tamponade after silicone oil removal. Intraoperative pneumatic retinal reattachment to assess relief of retinal traction combined with the production of widespread chorioretinal adhesions to wall off persistent anterior traction and detachment, as well as extended postoperative gas tamponade of the retina, appears to enhance the surgical results in retinal detachment complicated by proliferative vitreoretinopathy. Silicone oil tamponade of the retina appears to be useful in cases where retinal traction cannot be entirely relieved and in patients who are unable to tolerate the head positioning required for effective gas tamponade of the retina. A controlled clinical study recently begun will be required to define further the precise role of these methods of retinal tamponade.

Adult↗