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.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources

PubMed2000

Retinal vein thrombosis associated with chronic hepatitis C: a case series and review of the literature.

The role of procoagulant autoantibodies in hepatitis C virus (HCV) infection is unclear. Three individuals with HCV infection and a unique genetic hypercoagulable state developed retinal vein thrombosis (RVT) in association with interferon-alpha (IFN-alpha) therapy. It is probable that a combination of active HCV infection in a genetically susceptible individual receiving IFN-alpha accounted for the observed RVT.

Adult↗

PubMed1992

[Loss of ganglion cells in the retina secondary to vincristine therapy].

We report the case of a 25-year-old black female from Zaire with AIDS diagnosed 2 years earlier. Nine months before her death, she was treated for a disseminated Kaposi sarcoma with vincristin, adryamycin and bleomycin. At that time, visual acuity was normal and ophthalmologic examination was unremarkable except for the presence of bilateral Drusen and a cotton wool spot OS. Three months after the onset of chemotherapy, the patient complained of progressive visual field constriction, which progressed to blindness within a 4 month period. Five months after the onset of the tri-therapy a bilateral CMV retinitis developed, which was successfully treated by intravitreous injections of ganciclovir. This therapy was stopped as soon as blindness was established, with subsequent massive bilateral recurrence of the CMV retinitis. Histologic examination showed complete atrophy of the retinal ganglion cells and areas of CMV retinitis. The optic nerve was demyelinated and exhibited astrocytic gliosis. Immunohistochemistry confirmed the presence of CMV in infected retina and revealed the absence in the optic nerve of the class III beta-tubulin isotype and of the 200 kd neurofilament subunit. In contrast, oculomotor nerves appeared intact. The presence of HIV in the eye and in the optic nerve was excluded using PCR technique. The retinal ganglion cell loss and optic nerve atrophy appeared to be purely degenerative in nature, since there was no evidence of vascular occlusion, inflammation or retrobulbar compressive process. We therefore conclude that blindness was caused by vincristine therapy. The patient actually received 22 mg of vincristin intravenously in 11 courses over 7 months, although discontinuation was recommended by us after 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1993

Spatial and temporal differences between the expression of short- and middle-wave sensitive cone pigments in the mouse retina: a developmental study.

In an earlier study we found a topographic separation of middlewave-sensitive (M) and shortwave-sensitive (S) cones in the adult mouse retina. In the present study we investigated the development of the two colour-specific cone types to see whether there is also a temporal difference between the expression of the specific cone visual pigments. Using two anti-cone visual pigment antibodies, COS-1 and OS-2, we compared the densities of immunopositive cone outer segments on retinal whole mounts derived from mice of various ages. The first detectable cone outer segments were the S-cones which appeared in the inferior half of the retina on postnatal day 4. At this stage, the density of the S-cones was very low (30-40 cones/retina) but increased steadily on the following days to reach a value comparable to that of adults by P30 (18,000/mm2). This cone type always remained much more abundant in the lower part of the retina throughout the whole retinal development. In the superior half of the retina, a few S-cones appeared from postnatal day 7; however, their number always remained about one order of magnitude lower than in the inferior part. In contrast, M-cone outer segments were not identifiable earlier than postnatal day 11 and were confined exclusively to the superior part of the retina during the whole developmental process. On postnatal day 12, their density was 1,900/mm2 and increased to a value of 11,000/mm2 by postnatal day 30, which represented the adult stage. As shown by comparison of isodensity lines derived from immunocytochemical reactions of whole mount retinas, the two cone types occupied complementary halves of the mouse retina with maximum density centres located in opposite retinal quadrants. We conclude that 1) in contrast to the primate retina, mouse S-cones precede the M-cones in their development, and 2) the spatial arrangements of the two cone types is maintained throughout the whole differentiation process.

Animals↗

PubMed1992

A recombinant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retina.

Recombinant retroviruses encoding the histochemically detectable enzyme beta-galactosidase have been used to investigate lineage in the vertebrate nervous system. Identification of the descendants of individual progenitors is straightforward when progeny cells are arranged in a reproducible, clustered pattern, but difficulties in interpretation arise when progeny migrate extensively and/or in an irregular pattern. To better resolve clonal boundaries, additional histochemical marker viruses that engender distinctive reaction products can be used in combination with lacZ-bearing viruses. To this end, we have created a retrovirus vector, DAP, encoding an easily assayable enzyme, human placental alkaline phosphatase. DAP was found to be at least as useful as a lacZ-encoding retrovirus (e.g., BAG) with respect to high viral titer, stability of expression, and in identification of infected cells in vivo. Moreover, it was found to be neutral with respect to postnatal rodent retinal development and offered superior staining characteristics relative to lacZ. Coinfection of rodent retina with DAP and BAG allowed an examination of the clonal nature of radial arrays of labeled retinal cells that previously had been described as products of a single infected progenitor. Of 1100 radial arrays examined for the presence of both DAP- and BAG-infected cells, only 1.2% were the result of infection with more than one virus.

Alkaline Phosphatase↗

PubMed2004

Ciliary neurotrophic factor promotes muller glia differentiation from the postnatal retinal progenitor pool.

Ciliary neurotrophic factor (CNTF) exhibits multiple biological effects during vertebrate retinal development, including regulating the differentiation of photoreceptor cells and promoting the survival and axonal growth of ganglion cells. We report here that in addition to affecting the differentiation of retinal neurons, CNTF also promotes Muller glia genesis in the postnatal mouse retina. In both retinal monolayer and explant cultures, CNTF increases the number of progenitor cells adopting the Muller cell fate. Exogenous CNTF induces phosphorylation of signal transducers and activators of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) among neonatal progenitor cells and newborn Muller cells. In addition, increased levels of endogenous STAT3 and ERK phosphorylation have been observed at around postnatal day 5, coinciding with the peak of Muller glia genesis. Perturbation of STAT and ERK signaling using protein kinase inhibitors and a dominant-negative STAT3 mutant demonstrates that both CNTF-induced STAT and ERK activation are involved in promoting Muller cell production. Moreover, absorbing epidermal growth factor (EGF) signals with a neutralizing antibody did not affect CNTF-induced Muller glial genesis, indicating that the effect of CNTF is not mediated by the known Muller-enhancing activity of EGF. Together, these results support a novel function of CNTF-like cytokines in retinal gliogenesis.

Animals↗

PubMed1985

The topography of ganglion cell production in the cat's retina.

The ganglion cells of the cat's retina form several classes distinguishable in terms of soma size, axon diameter, dendritic morphology, physiological properties, and central connections. Labeling with [3H]thymidine shows that the ganglion cells which survive in the adult are produced as several temporally shifted, overlapping waves: medium-sized cells are produced before large cells, whereas the smallest ganglion cells are produced throughout the period of ganglion cell generation (Walsh, C., E. H. Polley, T. L. Hickey, and R. W. Guillery (1983) Nature 302: 611-614). Large cells and medium-sized cells show the same distinctive pattern of production, forming rough spirals around the area centralis. The oldest cells tend to lie superior and nasal to the area centralis, whereas cells in the inferior nasal retina and inferior temporal retina are, in general, progressively younger. Within each retinal quadrant, cells nearer the area centralis tend to be older than cells in the periphery, but there is substantial overlap. The retinal raphe divides the superior temporal quadrant into two zones with different patterns of cell addition. Superior temporal retina near the vertical meridian adds cells only slightly later than superior nasal retina, whereas superior temporal retina near the horizontal meridian adds cells very late, contemporaneously with inferior temporal retina. The broader wave of production of smaller ganglion cells seems to follow this same spiral pattern at its beginning and end. The presence of the area centralis as a nodal point about which ganglion cell production in the retinal quadrants pivots suggests that the area centralis is already an important retinal landmark even at the earliest stages of retinal development. This sequence of ganglion cell production differs markedly from that seen in the retinae of nonmammalian vertebrates, where new ganglion cells are added as concentric rings to the retinal periphery, and also bears no simple relationship to the cat's retinal decussation line. However, it can be related in a straightforward manner to the organization of axons in the cat's optic tract, suggesting that the fiber order in the tract represents a grouping of fibers by age.

Animals↗

PubMed2000

RINX(VSX1), a novel homeobox gene expressed in the inner nuclear layer of the adult retina.

The locus control region (LCR) of the human red and green visual pigment genes is critical for the formation of functional red and green cones in the retina. A 37-bp core of the LCR is perfectly conserved among mammals and binds specific retinal nuclear proteins. Here, we employed a yeast one-hybrid screen of an adult retinal cDNA library to clone and characterize these proteins. We identified clones encoding homeodomain (HD) transcription factors Pax6, Rx, and Chx10 and a novel paired-like HD protein, RINX. In the adult retina, RINX is exclusively expressed in a subset of cells (likely to be bipolar cells) of the retinal inner nuclear layer (INL). RINX is closely related to Chx10, which is also exclusively expressed in the INL of the adult retina and is critical for retinal development. The RINX gene is expressed in two classes of mRNA. One class encodes proteins that lack either part of or all of the HD, but retain the transcriptional activation domain. The RINX gene maps to chromosome 20p11.2 to which no retinal disease has been assigned. In conclusion, the LCR contains two adjacent motifs that are targets for binding of HD proteins that may specify the development and differentiation of cone photoreceptors and a subset of INL bipolar cells. Mutations in the related human CHX10 gene cause microphthalmia in a subset of families, and, therefore, the RINX gene is a candidate for this phenotype in another subset of patients. Since the RINX gene is likely an ortholog of the goldfish Vsx1 gene, it has been named VSX1 by the Human Gene Nomenclature Committee.

Adult↗

PubMed2002

Distinct functions of photoreceptor cell-specific nuclear receptor, thyroid hormone receptor beta2 and CRX in one photoreceptor development.

PURPOSE: To clarify the functions of a specific subtype of thyroid hormone receptor (TR), TRbeta2, and photoreceptor cell-specific nuclear receptor (PNR) in the development of cone photoreceptors. METHODS: The expression of short (S)- and medium (M)-wavelength cone opsins was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis in mice without a functional PNR (rd7/rd7 mice), and levels of plasma thyroid hormones and expression of TRbeta2 were also examined. Concomitantly, by means of reporter assays, the roles of PNR and TRbeta2 in the S- and M-cone opsin expression were explored at the transcriptional level. RESULTS: In rd7/rd7 mice, an abnormal increase in cone photoreceptors was observed immediately before retinal maturation normally occurs. Although an increase in S-cone opsin in the retina was observed during and after retinal development, the expression of M-cone opsin expression was not perturbed during retinal maturation. Plasma concentrations of thyroid hormone and levels of TRbeta2 expression in the rd7/rd7 mouse retina over the developmental period were normal. Transcriptional studies demonstrated that TRbeta2, but not PNR, activated the M-cone opsin gene promoter function, while suppressing the S-cone opsin promoter function enhanced by CRX in a thyroid hormone-dependent manner. CONCLUSIONS: The results indicate that PNR may suppress proliferation of cone photoreceptor progenitor cells and that the regulation of S- and M-cone opsin gene expression is mediated by TRbeta2 and CRX, but not by PNR. Thus, our results partly disclosed the molecular mechanism of cone photoreceptor development, highlighting the distinct functions of PNR and TRbeta2.

Animals↗

PubMed1999

Complications after implantation of intraocular devices in patients with cytomegalovirus retinitis.

PURPOSE: The authors report their surgical experience after sustained-release ganciclovir treatment, as well as replacing empty ganciclovir implants in patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis. METHODS: Between November 1995 and August 1998, 79 eyes of 49 patients received 99 intravitreal ganciclovir implants. Patients were examined monthly after implant surgery. Follow-up periods ranged from 6 to 128 weeks. RESULTS: At the first 3-week postoperative visit, 73 eyes (97.2%) of 46 patients exhibited stable conditions. In 6 eyes (3.8%) of 3 patients, further progression was noted due to resistance to ganciclovir. The most common early complication (within 6 weeks after implantation) was cystoid macular edema, observed in 7 eyes receiving implants. Retinal detachment was the most common late complication (over 6 weeks after implantation) in 11 eyes. In almost all eyes with CMV retinitis and retinal detachment, involvement of more than 25% of the retina was observed. Additional severe complications included extrusion of the first pellet in 2 eyes and cataract as a late complication in 5 eyes. A total of 28 eyes (35.4%) of 16 patients receiving a second implant did not experience significant three-line loss by the end of the follow-up period. CONCLUSION: In the treatment of CMV retinitis, sustained-release ganciclovir implantation seems to be an alternative to intravenous ganciclovir. Early implantation and additional replacement of the device has the potential to decrease the risk of developing retinal detachment. We would recommend additional systemic antiviral CMV therapy to avoid infection of the fellow eye and CMV disease.

AIDS-Related Opportunistic Infections↗

PubMed1990

Acetylcholinesterase activity as a marker for the development of the ciliary epithelium in the chicken embryo.

Specific histochemical staining for acetylcholinesterase was first visible in the presumptive ciliary epithelium on day 4 of embryonic development. The enzyme did not appear in the neural retina until day 6. The presence or absence of this enzyme activity enabled us to differentiate the presumptive ciliary epithelium from the adjacent presumptive neural retina early in development. In the rat embryo, acetylcholinesterase was not found in the ciliary epithelium at any stage, although its appearance in the neural retina followed a temporal pattern similar to that seen in chicken embryos. Weak AChE staining was seen in the ciliary epithelium of the rat by 15 days after birth. The function of acetylcholinesterase in the developing ciliary epithelium is unknown, but from the data currently available it is unlikely to be involved in the degradation of acetylcholine. Our observations suggest that some previous studies of retinal development may have misinterpreted events occurring in the embryonic ciliary epithelium as characteristics of the peripheral retina.

Acetylcholinesterase↗

PubMed2005

Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway.

An important step in retinal development is the positioning of progenitors within the eye field where they receive the local environmental signals that will direct their ultimate fate. Recent evidence indicates that ephrinB1 functions in retinal progenitor movement, but the signalling pathway is unclear. We present evidence that ephrinB1 signals through its intracellular domain to control retinal progenitor movement into the eye field by interacting with Xenopus Dishevelled (Xdsh), and by using the planar cell polarity (PCP) pathway. Blocking Xdsh translation prevents retinal progeny from entering the eye field, similarly to the morpholino-mediated loss of ephrinB1 (ref. 2). Overexpression of Xdsh can rescue the phenotype induced by loss of ephrinB1, and this rescue (as well as a physical association between Xdsh and ephrinB1) is completely dependent on the DEP (Dishevelled, Egl-10, Pleckstrin) domain of Xdsh. Similar gain- and loss-of-function experiments suggest that Xdsh associates with ephrinB1 and mediates ephrinB1 signalling through downstream members of the PCP pathway during eye field formation.

Adaptor Proteins, Signal Transducing↗

PubMed1980

Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations.

We observed the course of cytomegalovirus (CMV) retinitis in 21 eyes of 14 immunosuppressed patients. In two patients, other organisms, specifically Toxoplasma and Candida, also appeared to be causing retinal disease simultaneously. Post-mortem examination was done on 10 eyes from seven patients. At initial presentation, the retinitis was often asymptomatic and diagnosed during routine examination. The ophthalmoscopic picture was characteristic of cytomegalovirus; the early lesion was a small opaque, white granular area of retinal necrosis that spread in a centrifugal, brush-fire-like manner over 1 to 8 months. Vessel sheating and hemorrhages appeared as the disease progressed. In two patients new foci of retinitis developed remote from the original lesion. Four weeks to 4 months (average, 10 weeks) elapsed from the most extensive disease to total resolution. Resolution of active disease left a subtle retinal scar, and final visual acuity was reduced in one half the eyes. Repeated ophthalmoscopic examinations can aid in early diagnosis of CMV retinitis and in ascertaining which persons are most at risk for visual loss.

Candidiasis↗

PubMedDate not supplied

Regulation of proliferation, cell fate specification and differentiation by the homeodomain proteins Prox1, Six3, and Chx10 in the developing retina.

The coordination of proliferation and cell fate specification is of particular importance in the developing central nervous system, because different classes of neurons are generated at different stages of development. As a consequence, if too many or too few multipotent progenitor cells exit the cell cycle during the early stages of development, then a predictable shift in the ratio of neuronal cell types would occur. Such a perturbation could prove devastating for normal neural function. In the past several years, we have made numerous advances toward understanding the roles of cell cycle proteins in the development of the retina, a specialized region of the central nervous system. More recently, researchers have identified and characterized a number of homeodomain transcription factors that regulate the proliferation of retinal progenitor cells and the specification of cell fate. In this review, I will present recent findings about the homeodomain protein Prox1 and compare them with studies of two other homeodomain proteins that are important regulators of retinal development, Chx10 and Six3. Together, the research on the genes that encode these three proteins raises several new questions about the mechanisms underlying the coordination of proliferation and cell fate specification in the developing central nervous system.

Animals↗

PubMedDate not supplied

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behçet disease.

PURPOSE: To report a case of posterior uveitis with retinal neovascularization in a patient with Behçet disease treated with infliximab. METHODS: A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. RESULTS: Retinal neovascularization regressed 8 months after the first anti-tumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. CONCLUSIONS: The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behçet disease.

Adult↗

PubMed1976

Retinopathy of prematurity and retinal detachment.

A group of 39 patients with retinopathy of prematurity or retrolental fibroplasia have been evaluated. Nine of these were prematures at the time of their examination and showed severe bilateral disease. One eye in each patient was treated with the other eye serving as a control using either Xenon photocoagulation or cryocoagulation. It will take many years to observe the effect of this form of therapy but initial changes suggest alterations in the amount of retinal traction and in the appearance of blood vessels at the posterior pole in some of the treated patients. Thirty older patients have been assessed and of these, 18 eyes developed retinal detachments. Of the 16 operated upon, 87% had successful scleral buckling surgery. Three additional patients had similar retinal findings to retrolental fibroplasia but no history of prematurity or oxygen therapy. These patients were not included in this study. Retinopathy of prematurity is much less common now that it was 2 decades ago, but still represents a significant cause of ocular morbidity and blindness.

Adolescent↗

PubMed1999

A pitfall in the diagnosis of child abuse: external hydrocephalus, subdural hematoma, and retinal hemorrhages.

External hydrocephalus has been associated with subdural hematomas in infancy, and the hematomas have been noted to be secondary to minor trauma or have even been described as spontaneous. The author reports the case of an infant with external hydrocephalus who developed retinal as well as subdural hemorrhages after sustaining a minor head injury. Although retinal hemorrhage in infancy has been considered virtually pathognomonic of child abuse, in the setting of external hydrocephalus a more cautious interpretation may be appropriate.

Journal Article↗

PubMed2003

Reduced programmed cell death in the retina and defects in lens and cornea of Tgfbeta2(-/-) Tgfbeta3(-/-) double-deficient mice.

We have previously shown that immunoneutralization of transforming growth factor-beta (TGF-beta) in the chick embryo significantly reduces programmed cell death (PCD) in peripheral neurons, spinal cord, and retina. In order to validate these results we have begun to analyze PCD in mice with targeted ablations of the TGF-beta2 and TGF-beta3 genes. Recent analyses of mice lacking TGF-beta3 had failed to reveal an overt eye phenotype, while retinae of TGF-beta2-deficient mice showed retinal hypercellularity. We report now that eyes of Tgfbeta2/Tgfbeta3 double-deficient mice display severe alterations in the morphology of the retina, lens, and cornea. The inner neural retina-the region where TGF-beta receptor (TbetaR) I and II immunoreactivities are most prominent-is significantly thickened, and numbers of TUNEL-positive cells are significantly reduced compared to wild-type littermates. In Tgfbeta2(-/-) Tgfbeta3(-/-) and Tgfbeta2(-/-) Tgfbeta3(+/-) littermates the retina was consistently detached from the underlying pigment epithelium. Cornea, corneal stroma, and lens epithelium were significantly thinner in these mutants. In contrast, retinal morphology in Tgfbeta2(+/-) Tgfbeta3(-/-)mutant littermates resembles the situation observed in wild-type retinae except for the retinal detachment. Thus, regression in the thickness of cornea and corneal stroma seems to be TGF-beta isoform and gene dose dependent. Our results substantiate the notion based on previous analyses of chick embryos with reduced levels of endogenous TGF-beta that TGF-beta, most notably TGF-beta2, is required to mediate PCD in developing retinal cells in vivo. Moreover, our data indicate that TGF-betas play essential roles in cornea and lens development.

Activin Receptors, Type I↗

PubMed2006

Severe combined hyperlipidaemia and retinal lipid infiltration in a patient with Type 2 diabetes mellitus.

Severe combined hyperlipidaemia has occasionally been associated with infiltration of tissues in addition to arteries and the skin. We report a woman with Type 2 diabetes mellitus (DM) and severe combined hyperlipidaemia who developed retinal lipid infiltration, resulting in blindness. A 61-year-old woman with a 15-year history of Type 2 DM was admitted following a two-week history of progressive visual loss. Examination identified lipid infiltration into the retina. Phenotypically she had severe combined hyperlipidaemia with elevated IDL cholesterol and a broad beta band on lipoprotein electrophoresis, raising the possibility of familial dysbetalipoproteinaemia. However, gene sequencing analysis indicated that the patient was homozygous for the E3/E3 allele of the ApoE gene with no mutations detected in either the coding region or intron-exon boundaries. Her lipid profile improved following dietary therapy and gemfibrozil treatment, but this had little effect on either her fundal appearances or her visual acuity. Type 2 DM plays a vital role both in allowing expression of severe combined hyperlipoproteinaemia, in addition to serving as a risk factor for complications such as tissue infiltration.

Aged↗