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At least 1,243 records · Page 69Linked to original sources
PubMed1997

Apoptosis of retinal photoreceptors during development in vitro: protective effect of docosahexaenoic acid.

When rat retinal cells are cultured in a serum-free medium, the photoreceptor cells start dying after 7 days. The addition of docosahexaenoic acid (DHA) to the cultures prevents the selective death of photoreceptors. Here it is shown that, unlike other retinal neurons, photoreceptors die through an apoptotic pathway. Hallmarks of apoptosis, such as nuclear fragmentation and condensation and DNA cleavage forming a ladder pattern on an agarose gel, were observed. The timing and high selectivity of the triggering of photoreceptor cell apoptosis suggest the existence of a programmed cell death. Compared with other fatty acids, DHA not only was the most effective in promoting photoreceptor survival, but also the only one to decrease the number of apoptotic nuclei. The results suggest that DHA is important among the factors preventing apoptosis of photoreceptors in the developing retina. A limitation in the availability of this fatty acid might trigger apoptosis as a result of the failure to develop functional photoreceptor outer segments.

Animals↗
PubMed2006

Early retinal activity and visual circuit development.

Does spontaneous retinal activity prior to vision play a role in the establishment of visual maps? In this issue of Neuron, two separate papers by Huberman et al. and Hooks and Chen demonstrate a role for early spontaneous retinal activity in the establishment of ocular dominance columns and synaptic refinement at retinogeniculate synapses.

Action Potentials↗
PubMed1983

Retinal adhesion.

The development of retinal adhesion after coagulation has been investigated by the use of an experimental model of detachment in which fluid is injected into the retinal pigment interface. This adhesion, which varied from day to day in a predictable manner was low on the third day. The possible reasons for this are discussed.

Adhesiveness↗
PubMed1988

Development of cholinergic retinal neurons from embryonic chicken in monolayer cultures: stimulation by glial cell-derived factors.

In recent years evidence has indicated that, like the PNS, the development of the CNS is influenced by neuronotrophic polypeptide factors. In the present study, cultures of dissociated retinal neurons from 8-d-old chicken embryos were used to investigate the role of neuronotrophic factors (NTF) in the development of the neural retina. CAT, which in vivo is located in amacrine cells of the retina, served as a marker for studying the in vitro development of cholinergic retinal neurons. Differentiation of cholinergic cells under control conditions was indicated by a 10-fold increase of enzyme activity during a 7-d culture period. Addition of media conditioned by high-density retinal cultures resulted in a further stimulation of CAT activity by 100-400%. The CAT-stimulating activity was associated with a high-molecular-weight component of the retina conditioned medium (RCM) and was sensitive to protease treatment, but was not affected by other hydrolytic enzymes. The putative cholinergic factor was secreted by retinal cultures virtually free of neurons, suggesting that it is mainly produced by Müller cells. CAT-stimulating activity was also present in extracts from embryonic chicken retinae and medium conditioned by rat retinal cultures. NGF, anti-NGF antiserum, extracts from chicken brain tissues, and a number of other extracts and conditioned media, all known to contain neuronotrophic activities, were found to have no influence on cholinergic development in chicken retinal cultures. An extract from non-retinal eye tissue containing ciliary neuronotrophic factor (CNTF) stimulated CAT activity to the same extent as did RCM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Spontaneous retinal activity mediates development of ocular dominance columns and binocular receptive fields in v1.

The mechanisms that give rise to ocular dominance columns (ODCs) during development are controversial. Early experiments indicated a key role for retinal activity in ODC formation. However, later studies showed that in those early experiments, the retinal activity perturbation was initiated after ODCs had already formed. Moreover, recent studies concluded that early eye removals do not impact ODC segregation. Here we blocked spontaneous retinal activity during the very early stages of ODC development. This permanently disrupted the anatomical organization of ODCs and led to a dramatic increase in receptive field size for binocular cells in primary visual cortex. Our data suggest that early spontaneous retinal activity conveys crucial information about whether thalamocortical axons represent one or the other eye and that this activity mediates binocular competition important for shaping receptive fields in primary visual cortex.

Action Potentials↗
PubMed1990

In ovo and in culture development of chick retinal angiotensin converting enzyme.

The activity of angiotensin I-converting enzyme (ACE, EC 3.4.15.1), measured using Hip-His-Leu as substrate, was determined in the developing chick retina, and in monolayer and aggregate cultures of embryonic retinal cells. ACE specific activity in chick retinal homogenate increased 86-fold from embryonic day 13 until the 7th post-hatching day. The development of ACE activity occurred in parallel with that reported for synapse and photoreceptors. ACE activity expression in aggregates, but not in monolayer culture, was similar to that observed in the developing retina in ovo. At culture, day 13, ACE specific activity was 11.8-fold higher in the aggregate than in the dispersed cell culture, and was comparable to that in a 21-day-old embryonic intact retina. Our results suggest that histotypic association of retinal cells during development may be an important event controlling the expression of ACE activity in the CNS.

Animals↗
PubMed1996

Transient retinal ganglion cells in the developing rat are characterized by specific morphological properties.

To determine whether dendritic development of mammalian retinal ganglion cells (RGCs) is affected by axonal target specificity, the morphology of three populations of maturing RGCs was examined. These included RGCs that exhibited either a transient, topographically incorrect, projection to the caudal superior colliculus (SC), or a transient projection to the caudal inferior colliculus (IC), in addition to a control group that exhibited a topographically correct projection to the caudal SC. Projection populations were identified by retrograde transport of rhodamine labeled latex microspheres injected into target nuclei. Labeled RGCs were then injected in vitro with Lucifer yellow to reveal the details of their dendritic morphology. Retinal ganglion cells making target errors, most of which ultimately die, were found to undergo a remarkable degree of morphological differentiation and could be categorized according to the adult type I, II, or III criteria. However, the relative proportions of these cell types were different among RGCs making transient connections versus those whose projections were preserved. Approximately half of the RGCs making topographically incorrect projections to the SC belonged to type III, in contrast to 6% that made a topographically correct projection. In addition, the population of cells sending axons to caudal IC did not include type III RGCs, but consisted of small type II neurons. The development of the basic dendritic form of each RGC type was only modestly influenced by its projection pattern; dendritic trees of cells making transient projections were essentially normal with only a slight, but statistically significant, reduction in dimensions. Moreover, dendritic remodeling was evident during maturation of neurons making either transient or normal projections. Together, these findings indicate that target specificity plays a relatively minor role on dendritic development of retinal ganglion cells.

Animals↗
PubMed1995

Development of the retinal circulation in the pig.

Retinal angiogenesis was studied in 300 eyes of 150 porcine fetuses by means of semithin histologic sections and vascular corrosion casts. In the embryonic and early fetal period, the retina is avascular and nourished via diffusion from the choriocapillaris and the vascular tunic of the lens. The development of the inner vascular plexus of the retina occurs in three different stages. In the first stage (angioblast phase), during gestational weeks 6-7, mesenchymal precursor cells arising from the arterial and venous circle around the optic nerve invade the nerve fiber layer of the retina via the otic disc border. They form a network of angioblasts that gives rise to an immature capillary network in the second stage (angiogenesis phase). This vascular monolayer is located within the nerve fiber layer and reaches the ora serrata around gestational weeks 9-10. Initially, the immature retinal capillaries have an irregular appearance with wide lumina and relatively small intercapillary meshes. Subsequently, the lumina become smaller by involution and atrophy. In the third stage (maturation and remodeling phase) the immature blood vessels differentiate into retinal arterioles, capillaries and venules. From gestational week 11 onwards, the larger retinal arterioles are surrounded by a distinct periarteriolar capillary-free zone. The three stages start at the optic disc and extend centrifugally towards the retinal periphery. The development of the outer vascular plexus is essentially different from the angiogenesis of the inner vascular plexus. The outer retinal vessels that are located in the inner nuclear layer arise from previously developed capillaries and venules located in the inner vascular plexus. Moreover, the development of the outer vascular plexus starts at the macula and proceeds along with the maturation of the neural retina.

Animals↗
PubMed2001

Variegated expression and delayed retinal pigmentation during development in transgenic mice with a deletion in the locus control region of the tyrosinase gene.

Deletion of the tyrosinase locus control region (LCR) in transgenic mice results in variegated expression in the skin. Here we investigate the pigmentation pattern of other tissues that express tyrosinase: iris, choroid, and retina in the same animals. A mosaic distribution of pigmentation appears in the iris and choroid. Interestingly, a markedly different mosaic pattern is found in the retina, where central areas contain little or no melanin while pigmentation rises to normal levels towards periphery. Further, there is a temporal delay in the initiation and accumulation of pigment in retinal pigmented epithelium (RPE) cells during development, and patterns of adult retinal melanisation in these mice appear arrested at a stage found in early embryogenesis in wild-type mice. These results demonstrate that the tyrosinase LCR is needed for the correct establishment and maintenance of this expression domain throughout development, but particularly during the later stages of retinal melanisation.

Alleles↗
PubMed2001

The Ath5 proneural genes function upstream of Brn3 POU domain transcription factor genes to promote retinal ganglion cell development.

During retinogenesis, the Xenopus basic helix-loop-helix transcription factor Xath5 has been shown to promote a ganglion cell fate. In the developing mouse and chicken retinas, gene targeting and overexpression studies have demonstrated critical roles for the Brn3 POU domain transcription factor genes in the promotion of ganglion cell differentiation. However, the genetic relationship between Ath5 and Brn3 genes is unknown. To understand the genetic regulatory network(s) that controls retinal ganglion cell development, we analyzed the relationship between Ath5 and Brn3 genes by using a gain-of-function approach in the chicken embryo. We found that during retinogenesis, the chicken Ath5 gene (Cath5) is expressed in retinal progenitors and in differentiating ganglion cells but is absent in terminally differentiated ganglion cells. Forced expression of both Cath5 and the mouse Ath5 gene (Math5) in retinal progenitors activates the expression of cBrn3c following central-to-peripheral and temporal-to-nasal gradients. As a result, similar to the Xath5 protein, both Cath5 and Math5 proteins have the ability to promote the development of ganglion cells. Moreover, we found that forced expression of all three Brn3 genes also can stimulate the expression of cBrn3c. We further found that Ath5 and Brn3 proteins are capable of transactivating a Brn3b promoter. Thus, these data suggest that the expression of cBrn3c in the chicken and Brn3b in the mouse is initially activated by Ath5 factors in newly generated ganglion cells and later maintained by a feedback loop of Brn3 factors in the differentiated ganglion cells.

Animals↗
PubMed1995

Protein tyrosine phosphatases expressed in developing brain and retinal Müller glia.

Regulation of protein function through tyrosine phosphorylation is critical to many developmental processes involving cell-cell communication. A number of protein tyrosine phosphatases (PTPs) have been identified in the early postnatal and mature central nervous system (CNS), but the PTPs expressed during its development have not been well characterized. Using a polymerase chain reaction with degenerate primers, we analyzed PTPs expressed in fetal (E18) rat brain and Müller glia cultures from embryonic chick retina, two systems in which cell-to-cell contacts are numerous. Fetal rat brain expressed four known receptor-like PTPs (PTP delta, LAR, LAR-PTP2, LRP (PTP alpha)) and the non-receptor phosphatase PTP1B. Müller glia exhibited a distinct but overlapping pattern of expression: four known receptor PTPs (PTP alpha, PTP gamma, PTP delta, PTP zeta) and PTP1B. In addition, two novel PTPs, termed MG-PTP1 and 2 (Müller glia PTP 1 and 2) were identified in Müller glia cDNA. MG-PTP1 was related to, but distinct from PTP delta, while MG-PTP2 was related to, but distinct from the cytosolic T-cell phosphatase. These results demonstrate that a distinct but overlapping set of PTPs is expressed in the developing brain and retinal Müller glia, including two novel PTPs that may participate in neural cell communication.

Animals↗
PubMed2000

Therapeutic developments in cytomegalovirus retinitis.

The incidence of cytomegalovirus (CMV) retinitis in AIDS has declined significantly due to the use of highly active antiretroviral therapy (HAART). However, patients with HIV, especially those failing HAART, may still suffer with CMV retinitis, which can lead to significant loss of vision and blindness. Ganciclovir has traditionally been considered the recommended treatment for CMV retinitis; however, due to side effects and the possibility of developing viral resistance, other agents may be preferred in certain situations. Foscarnet, which has similar efficacy to ganciclovir but a different side effect profile, is more difficult to administer and is less well-tolerated. Intravenous cidofovir, which may be more effective than either iv. ganciclovir or foscarnet, can also be used as a first line agent; however, it is associated with toxicity (renal and ocular) and thus needs careful use. Local therapy for CMV retinitis has been a significant advance. The intraocular ganciclovir implant has the highest efficacy of the approved agents and is well-tolerated. Fomivirsen, an oligonucleotide injected intravitreally, is a newly approved agent which offers alternative treatment. Intravitreal ganciclovir or foscarnet, although not approved, have been used successfully in some patients especially those with recurrent or refractory disease. The development of new anti-CMV agents has been stalled by the decreased incidence of the disease. Valganciclovir, a prodrug of ganciclovir, offers excellent oral bioavailability and is the closest to approval of all the new anti-CMV drugs. High ganciclovir blood levels are achieved without the complications associated with the requirement for long-term iv. access. The monoclonal antibody (mAb) MSL-109, did not offer a significant advantage when added to traditional anti-CMV therapy. Development plans of other agents such as cyclic HPMPC and lobucavir have been put on hold by their respective manufacturers. Adefovir is a nucleotide analogue that possesses anti-CMV activity, but is currently only being pursued for the treatment of hepatitis B virus. Other compounds possessing significant anti-CMV activity, including BAY 38-4766 and GW1263W94 are still in the early stages of development.

Adenine↗
PubMed1995

Retinal ellipsosomes: morphology, development, identification, and comparison with oil droplets.

We report some unique features of retinal cone ellipsosomes in mountain-stream teleosts. They have also been compared with oil droplets occurring predominantly in many reptilian and avian retinas. Ontogenetically, ellipsosome differentiation from ellipsoidal mitochondria occurs with advanced eye growth (diameter > 1 mm). In juvenile loaches, they arise almost simultaneously in the dorsal and ventral retina, whereas in cyprinids, they appear first dorsally in bottom-dwelling early juveniles (approximate age 3-4 months), and then in the ventral retina in migratory late juveniles (eye diameter > 4 mm, approximate age 2 years). The significance of the pattern of ontogeny of ellipsosomes in these stream fishes is discussed in relation to their utilization of a complex habitat during life. All adult cones possess conspicuous ellipsosomes. Histochemically, they react strongly with phosphotungstic-acid hematoxylin, a dye specific for proteins, whereas oil droplets refuse to do so (studied in turtle and pigeon). This reflects a major chemical difference between the two types of globules. Since ellipsosomes are present in the double cone accessory unit (which in higher vertebrates lacks an oil droplet) and since they appear late ontogenetically during advanced eye growth, they cannot be related to oil droplets, which have an embryonic developmental program.

Animals↗
PubMed1990

Morphological changes in the zonula adhaerens during embryonic development of chick retinal pigment epithelial cells.

Retinal pigment epithelial cells from chicks at various stages of development were examined by transmission electron microscopy to determine how the adult form of the zonula adhaerens, composed of subunits termed zonula adhaerens complexes, is acquired. During early stages of development, between embryonic day 4 and embryonic day 7, the intermembrane discs of zonula adhaerens complexes appear to be formed from material already present between the junctional membranes of the zonulae adhaerentes. In contrast, the cytoplasmic plaque material of the zonulae adhaerentes is difficult to detect before hatching; it is seen as a dense band along the junctional membranes at hatching and as individual subunits in register with the intermembrane discs in adult retinal pigment epithelial cells. After embryonic day 16, when the zonulae adhaerentes increase dramatically in size, single zonula adhaerens complexes are also present basal to the zonulae adhaerentes along the lateral cell membrane. This suggests that, during later stages of development, the junctions grow in size and/or turn over by the addition of pre-assembled zonula adhaerens complexes.

Animals↗
PubMed2006

The development of a multichannel electrode array for retinal prostheses.

The development of a multielectrode array is the key issue for retinal prostheses. We developed a 10 x 10 platinum electrode array that consists of an 8-microm polyimide layer sandwiched between 5-microm polymonochloro-para-xylylene (parylene-C) layers. Each electrode was formed as a 30-microm-high bump by Pt/Au double-layer electroplating. We estimated the charge delivery capability (CDC) of the electrode by measuring the CDCs of two-channel electrode arrays. The dimensions of each electrode of the two-channel array were the same as those of each electrode formed on the 10 x 10 array. The results suggest that for cathodic-first (CF) pulses, 80% of electrodes surpassed our development target of 318 microC/cm2, which corresponds to the charge density of pulses of 500 micros duration and 200 microA amplitude for a 200-microm-diameter planar electrode.

Electrodes, Implanted↗
PubMed1978

Fellow eyes of giant retinal breaks.

INCIDENCE OF RETINAL BREAKS AND DETACHMENT IN FELLOW EYES. The fellow eyes of 226 giant retinal breaks were followed in order to determine the incidence and natural course of chorioretinal and vitreous pathology. During the period of observation which ranged from 18 months to 16 years, the incidence of retinal breaks and retinal detachment increased from 36.1 percent to 51.3 percent. By the end of the follow-up period, the incidence of bilateral giant retinal breaks was 12.8 percent; retinal tears 11.9 percent, retinal holes 10.2 percent, retinal dialysis 0.4 percent, and retinal detachment 15.9 percent. The average duration of follow-up was 3.7 years, therefore, the incidence of retinal breaks in fellow eyes is probably significantly higher. VITREORETINAL CHANGES PRECEDING THE DEVELOPMENT OF RETINAL BREAKS. Syneresis, liquefaction, and condensation of the vitreous base were observed in the majority fellow eyes that developed retinal tears or giant retinal breaks. Follow-up of fellow eyes revealed that the development of a giant retinal break is often preceded by increasing white with pressure associated with increasing condensation of the vitreous base. MANAGEMENT OF FELLOW EYES. Bcause of the high incidence of retinal breaks developing in the fellow eye, regular and thorough examination of the vitreous and retinal breaks even though the fundus may appear normal at the initial examination. PROPHYLACTIC TREATMENT. This study suggests that prophylactic treatment is beneficial in the management of fellow eyes of giant retinal breaks. During this study, retinal breaks developed in 27.3 percent of untreated eyes and in 2.4 percent of eyes treated prophylactically. PROPHYLACTIC TREATMENT OF FELLOW EYES OF GIANT RETINAL BREAKS. Its seems prudent to prophylactically treat retinal holes or dialyses in eyes without retinal detachment with cryotherapy. Scleral bucking seems justified in the prophylactic treatment of eyes with retinal tears of lattice-like degeneration with retinal breaks or highly myopic eyes with increasing white with pressure and increasing condensation of the vitreous base.

Adolescent↗
PubMedDate not supplied

Possible role of HHV-6 in the development of AIDS retinitis.

Majority of AIDS patients experience visual loss due to AIDS-associated retinitis or commonly known as CMV retinitis. It has been reported that CMV infection of the retina is a late manifestation of AIDS and a poor prognostic sign. The etiology and mechanism(s) involved in the development of AIDS-associated retinitis is currently unknown. It is of critical importance to understand the pathobiology of this disease process in order to develop a rational approach to therapeutic intervention. We have determined the frequency and proximity of simultaneous occurrence of HIV-1 and HHV-6 in retinal tissues of AIDS patients in the absence of CMV infection. Active infection of HIV-1 has been identified in the retinal tissues of 30-60% of AIDS patients analyzed. HHV-6 antigens and transcripts were detectable in about 50% of HIV-1 positive retinas. Most significant finding of our studies is the presence of HIV-1 and HHV-6 antigens and transcriptional activity in retinal tissue in the absence of CMV infection. These observations suggest that HIV-1 in association with HHV-6 may predispose certain retinal cells to other opportunistic agents such as CMV in late stages of AIDS-associated retinitis.

AIDS-Related Opportunistic Infections↗