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At least 955 records · Page 53Linked to original sources
PubMed2005

The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina.

BACKGROUND: With the advent of genome-wide analyses, it is becoming evident that a large number of noncoding RNAs (ncRNAs) are expressed in vertebrates. However, of the thousands of ncRNAs identified, the functions of relatively few have been established. RESULTS: In a screen for genes upregulated by taurine in developing retinal cells, we identified a gene that appears to be a ncRNA. Taurine Upregulated Gene 1 (TUG1) is a spliced, polyadenylated RNA that does not encode any open reading frame greater than 82 amino acids in its full-length, 6.7 kilobase (kb) RNA sequence. Analyses of Northern blots and in situ hybridization revealed that TUG1 is expressed in the developing retina and brain, as well as in adult tissues. In the newborn retina, knockdown of TUG1 with RNA interference (RNAi) resulted in malformed or nonexistent outer segments of transfected photoreceptors. Immunofluorescent staining and microarray analyses suggested that this loss of proper photoreceptor differentiation is a result of the disregulation of photoreceptor gene expression. CONCLUSIONS: A function for a newly identified ncRNA, TUG1, has been established. TUG1 is necessary for the proper formation of photoreceptors in the developing rodent retina.

Amino Acid Sequence↗
PubMed1998

Retinal detachment following intracapsular cataract extraction. A 10-year follow-up study.

PURPOSE: To examine the incidence of and risk factors for retinal detachment during a 10-year follow-up on intracapsular cataract extraction (ICCE). METHODS: Retrospective analysis of medical records of 1041 eyes operated on with ICCE in the years 1984-86. A complete follow-up was achieved, and actuarial methods were used in the risk assessment. The risk time averaged 82 months. RESULTS: Twenty-two (2.1%) eyes developed retinal detachment; half of the cases occurred during the first postoperative year, but new cases emerged throughout the period. The cumulative incidence of RD amounted to 2.8%; 95% confidence interval: 1.5-4.2%. Multivariate Cox regression analysis identified younger age at surgery (relative risk for each 10-year increase in age=0.6; 95% confidence interval: 0.39-0.95) and male gender (relative risk=2.5; 95% confidence interval 1.04-6.04) as significant risk factors for RD. Eleven eyes, 50% of eyes with RD and 1% of the total number of eyes, lost useful vision in spite of retinal surgery. CONCLUSION: Even though the risk for both RD and an unfavourable result following retinal surgery may be smaller using contemporary surgical techniques, the present study indicates a substantial morbidity following cataract surgery, when a sufficiently long observation period is considered.

Age Distribution↗
PubMed1981

The emergence, localization, and maturation of neurotransmitter systems during development of the retina in Xenopus laevis: II. Glycine.

The high-affinity uptake and release of glycine was studied in retinas of Xenopus laevis. In the toad and tadpole retina, 3H-glycine was accumulated by a population of cells located predominantly in the inner nuclear layer. When retinas preloaded with 3H-glycine were subjected to high K+-concentrations, these retinas released large amounts of 3H-glycine by a Ca++-dependent mechanism. The appearance and maturation of these putative glycinergic properties was followed during retinal development. Our results indicate that the high-affinity uptake of glycine first appears around stage 33/34 whereas K+-stimulated glycine release cannot be detected until stage 42.

Animals↗
PubMed2006

Expression of olig2 in retinal progenitor cells.

Olig2 is a basic helix-loop-helix transcription factor that is specifically expressed in oligodendrocyte precursors in the central nervous system. Owing to the absence of oligodendrocytes in the retina, however, the role of olig2 in retinal development remains unclear. In the present study, we demonstrated for the first time that olig2 is expressed in embryonic and postnatal mouse retina. Interestingly, a subset of the bromodeoxyuridine-positive cells expressed olig2 in the embryonic retina. On the other hand, olig2-positive cells did not express nestin, neuron-specific class III beta-tubulin, neurofilament, or various retinal cell-type-specific markers. These results suggest that olig2 is involved in the maintenance of the undifferentiated state of retinal progenitor cells.

Animals↗
PubMed1993

Wegener's granulomatosis with rapidly progressive retinitis and anterior uveitis.

A case of a Wegener's granulomatosis with severe retinitis and anterior uveitis is presented. The diagnosis of Wegener's granulomatosis was based on the clinical features and on histologic findings of multiple lesions. Anterior uveitis and severe retinitis developed in both eyes, resulting in decreased visual acuity. This case indicates that thorough examinations of the ocular fundus should be performed routinely during the follow-up of patients with Wegener's granulomatosis.

Cytomegalovirus Retinitis↗
PubMed2001

Regulation of choroid development by the retinal pigment epithelium.

PURPOSE: The choroidal vasculature is essential for normal retinal function. However, mechanisms that control choroid development are unknown. In the present study, we provide evidence that the retinal pigment epithelium (RPE) plays an essential role in regulation of the choroid development in the mouse eye. METHODS: Transgenic mice that transiently express FGF9 in the embryonic RPE were generated. Postnatal eyes were analyzed by histology and in situ hybridizations. RESULTS: In the transgenic mice, most of the RPE was converted to neural retina. The choroid formed only in regions where patches of RPE were present. The choroid failed to develop in the absence of the RPE. CONCLUSIONS: The presence of the RPE appears to be required for choroid development, suggesting that molecular interactions between RPE and periocular mesenchyme are essential for melanocyte differentiation and vascular development in the choroid.

Animals↗
PubMed1999

Extrinsic and intrinsic factors control the genesis of amacrine and cone cells in the rat retina.

The seven major classes of cells of the vertebrate neural retina are generated from a pool of multipotent progenitor cells. Recent studies suggest a model of retinal development in which both the progenitor cells and the environment change over time (Cepko, C. L., Austin, C. P., Yang, X., Alexiades, M. and Ezzeddine, D. (1996). Proc. Natl. Acad. Sci. USA 93, 589-595). We have utilized a reaggregate culture system to test this model. A labeled population of progenitors from the embryonic rat retina were cultured with an excess of postnatal retinal cells and then assayed for their cell fate choices. We found that the postnatal environment had at least two signals that affected the embryonic cells' choice of fate; one signal inhibited the production of amacrine cells and a second affected the production of cone cells. No increase in cell types generated postnatally was observed. The source of the inhibitor of the amacrine cell fate appeared to be previously generated amacrine cells, suggesting that amacrine cell number is controlled by feedback inhibition. The progenitor cell lost its ability to be inhibited for production of an amacrine cell as it entered M phase of the cell cycle. We suggest that postmitotic cells influence progenitor cell fate decisions, but that they do so in a manner restricted by the intrinsic biases of progenitor cells.

Animals↗
PubMed2003

Ibuprofen improves oxygen-induced retinopathy in a mouse model.

PURPOSE: Retinopathy of prematurity is a developmental vascular anomaly occurring in the incompletely vascularized retina of the premature infant. Ibuprofen is a nonsteroidal anti-inflammatory agent similar to indomethacin, but with less pronounced side-effects. The goal of the study was to test the hypothesis that ibuprofen would improve oxygen-induced retinopathy in a mouse model. METHODS: C57BL6 mice pups were exposed to 75% oxygen from postnatal day 7 through postnatal day 12. Ibuprofen was administered along with oxygen exposure as a single subcutaneous dose of 40 mg/kg/day for 5 days. Animals were sacrificed on postnatal day 17 through postnatal day 20. The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein-conjugated dextran-perfused retinal flat mounts and by quantitation of extra-retinal nuclei by use of periodic acid-Schiff-stained retinal sections. RESULTS: Animals that received ibuprofen during hyperoxia exposure had a significantly lower median (25th, 75th quartile) retinopathy score of 6 (5, 7.5) compared with animals that received oxygen only, with a score of 12 (10.5, 12.5), with p < 0.005. Animals given ibuprofen during hyperoxia exposure had a significantly lower extra-retinal nuclei count per section (14.2 +/- 3.6) compared with animals that were only exposed to oxygen (26.8 +/- 5.8), with p < 0.005. Ibuprofen did not affect the growth of the animals. CONCLUSION: Ibuprofen improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development of the animals.

Animals↗
PubMed2005

Long-chain (n-3) polyunsaturated fatty acids are more efficient than alpha-linolenic acid in improving electroretinogram responses of puppies exposed during gestation, lactation, and weaning.

Long-chain PUFAs (LCPUFAs) are essential for proper neural and retinal development in many mammalian species. We investigated puppies born to dogs fed diets containing varying amounts of vegetable and marine (n-3) fatty acids during gestation/lactation. The fatty acid compositions of dogs' milk and puppy plasma phospholipids were evaluated, and electroretinographic responses of the young dogs were determined after they were weaned to the same diets. Dogs' milk fatty acid composition reflected the diets fed during gestation/lactation. The milk of dogs fed a high alpha-linolenic acid (ALA) diet was enriched in ALA but not docosahexaenoic acid (DHA). Puppies fed this ALA-enriched milk accumulated more plasma phospholipid DHA than the low (n-3) fatty acid group. However, this accumulation was less than that obtained in puppies fed preformed DHA during development and suckling (P < 0.05). Electroretinograms (ERGs) of 12-wk-old puppies revealed significantly improved visual performance in dogs fed the highest amounts of (n-3) LCPUFAs (P < 0.05). These puppies demonstrated improved rod response (improved amplitude and implicit time of the a-wave, P < 0.05). Puppies from the low (n-3) fatty acid group exhibited the poorest ERG responses compared with the high-marine or high-vegetable (n-3) groups. A novel parameter devised in this study, the initial intensity at which the a-wave was detectable (i.e., threshold intensity), also demonstrated that retinal response of puppies consuming the (n-3) LCPUFA-containing diets occurred at lower light intensity, thereby exhibiting greater rod sensitivity, than the other diet groups. These findings indicate that preformed dietary (n-3) LCPUFA is more effective than ALA in enriching plasma DHA during perinatal development and results in improved visual performance in developing dogs.

Animals↗
PubMed2004

Roles of the bHLH gene Hes1 in retinal morphogenesis.

During retinal development, common precursors give rise to various types of cells in a time course specific to each cell type. Previously, we demonstrated that the bHLH gene Hes1 inhibits neuronal differentiation whereas, in Hes1-null retina, precursors prematurely differentiate into neurons and form abnormal rosette-like structures. Thus, Hes1 is essential for maintenance of precursors and morphogenesis of the neural retina. However, the precise causal link between premature differentiation and abnormal structures remains to be determined. Here, we found that misexpression of Hes1 in the developing retina promotes formation of undifferentiated precursor-like cells, whereas in Hes1-null retina, precursors are not properly maintained and prematurely differentiate into ganglion cells. Strikingly, those prematurely differentiated ganglion cells erupt into the subretinal space through the regions where precursors and the outer limiting membrane are lost. These results indicate that Hes1 maintains precursors and the outer limiting membrane and thereby regulates retinal morphogenesis.

Animals↗
PubMed2003

Analysis of EphB receptors and their ligands in the developing retinocollicular system of the wallaby reveals dynamic patterns of expression in the retina.

The expression of EphB1 and B2 receptors and ephrins-B1, -B2 and -B3 in the retina and superior colliculus of the wallaby (Macropus eugenii) was examined during the development of the retinocollicular projection, using reverse transcription-polymerase chain reaction and immunohistochemistry. There was an early transient differential expression of EphB2 that was higher in ventral retina and restricted to the outer neuroblast layer, whereas a high ventral to low dorsal gradient of ephrin-B2 expression occurred there throughout the study period. However, there was no dorsoventral gradient of receptors or ligands in retinal ganglion cells or a mediolateral gradient of ephrins in the colliculus. These findings suggest a limited role for these molecules in topographic mapping across the mediolateral colliculus in the wallaby. Early in retinal development there is a complementary pattern of expression of ephrin-B1 and -B2 in the outer neuroblast layer that overlaps with expression of EphB2. Ganglion and amacrine cells also express EphB2. As development proceeds subpopulations of putative horizontal and bipolar cells, also expressing EphB2, come to reside in the inner nuclear layer and ephrin-B1 is expressed throughout the outer nuclear layer. At the same time cells expressing ephrin-B2, and subpopulations of horizontal and bipolar cells come to reside in the inner nuclear layer and there is a corresponding decrease in ephrin-B2 expression in the outer nuclear layer. This pattern of coexpression of receptors and ligands suggests a role for them in cell migration and maintenance of laminar boundaries.

Aging↗
PubMed2004

Proteolytic shedding of the extracellular domain of photoreceptor cadherin. Implications for outer segment assembly.

Photoreceptor cadherin (prCAD) is a distinctive cadherin family member that is concentrated at the base of rod and cone outer segments and is required for their structural integrity. During retinal development, prCAD localizes to the site of the future outer segment before rhodopsin or other phototransduction proteins. In vivo, prCAD undergoes a single proteolytic cleavage that releases the ectodomain as a soluble fragment. The C-terminal fragment containing the transmembrane and cytosolic domains remains associated with the outer segment. In rds(-/-) retinas, in which outer segment assembly is severely disrupted because of the absence of retinal degeneration slow (RDS)/peripherin, an essential outer segment structural protein, the level of prCAD is increased, whereas the levels of other outer segment proteins are decreased relative to wild type retinas. Additionally, the ratio of intact:cleaved prCAD polypeptides is increased in rds(-/-) retinas. These data imply that prCAD ectodomain cleavage is an integral part of the outer segment assembly process, and they further suggest that outer segment assembly might be driven, at least in part, by the near irreversibility of proteolysis.

Amino Acid Sequence↗
PubMed2002

Emergence of multiple drug-resistant human cytomegalovirus variants in 2 patients with human immunodeficiency virus infection unresponsive to highly active antiretroviral therapy.

In 2 patients infected with human immunodeficiency virus (HIV), highly active antiretroviral therapy was unable to suppress HIV replication as a result of the emergence of drug-resistant HIV variants. Human cytomegalovirus (HCMV) retinitis developed in both patients, and an unusually complex mixture of drug-resistant HCMV variants was detected in both patients.

AIDS-Related Opportunistic Infections↗
PubMed2006

Making the gradient: thyroid hormone regulates cone opsin expression in the developing mouse retina.

Most mammals have two types of cone photoreceptors, which contain either medium wavelength (M) or short wavelength (S) opsin. The number and spatial organization of cone types varies dramatically among species, presumably to fine-tune the retina for different visual environments. In the mouse, S- and M-opsin are expressed in an opposing dorsal-ventral gradient. We previously reported that cone opsin patterning requires thyroid hormone beta2, a nuclear hormone receptor that regulates transcription in conjunction with its ligand, thyroid hormone (TH). Here we show that exogenous TH inhibits S-opsin expression, but activates M-opsin expression. Binding of endogenous TH to TRbeta2 is required to inhibit S-opsin and to activate M-opsin. TH is symmetrically distributed in the retina at birth as S-opsin expression begins, but becomes elevated in the dorsal retina at the time of M-opsin onset (postnatal day 10). Our results show that TH is a critical regulator of both S-opsin and M-opsin, and suggest that a TH gradient may play a role in establishing the gradient of M-opsin. These results also suggest that the ratio and patterning of cone types may be determined by TH availability during retinal development.

Animals↗
PubMed1983

Synaptic interactions in the GABA system during postnatal development in retina.

Using biochemical analyses, we have demonstrated the presence of a high-affinity, sodium- and temperature-dependent uptake system for GABA in the retinas of newborn rabbits. The activity of this system two days after birth is approximately 70 percent of adult values, slowly increasing to adult level by postnatal day 6-8. An intraocular injection nipecotic acid (final concentration = 10 mM) into one-day-old rabbit pups resulted in a 60 percent inhibition in uptake activity. In order to study the possible role of the GABA uptake system in retinal development, we have determined the consequences of blocking GABA uptake with nipecotic acid on the postnatal development of post-synaptic GABA receptors, as measured by 3H-muscimol binding. Nipecotic acid treatment caused a significant increase in receptor binding in retinas prior to eye opening, with the maximal stimulation being one day after the intraocular injection. Our data indicate that the development of GABA receptor sites is influenced by the activity of the GABA uptake system and suggest that GABA may function as a trophic factor in the developing rabbit retina.

Animals↗
PubMed2000

Contact lens electroretinography in preterm infants from 32 weeks after conception: a development in current methodology.

AIM: To assess the feasibility of using a contact lens electrode to record the electroretinogram (ERG) in preterm infants less than 35 weeks after conception. METHODS: The ERG was recorded from seven very low birthweight preterm infants on a total of 14 occasions using an infant monkey contact lens electrode. Age at recording the first ERG ranged from 23 to 51 days (gestational age 32-34 weeks), and weight ranged upwards from 1100 g. RESULTS: No complications were observed. With advancing age and maturity the dark adapted rod threshold decreased, indicating increased retinal sensitivity. CONCLUSIONS: Contact lens recording of the ERG from extremely small immature preterm infants is a practicable and well tolerated procedure. This method of recording the ERG will enable further evaluation of retinal development in this vulnerable population.

Birth Weight↗
PubMed1990

Consequences for retinal growth when vision occurs in S2 space.

We postulate that the process of vision occurs in the S2 space. The retina is endowed with the topology of a part of a two-sphere S2, roughly, the topology of a hemisphere. There is a corresponding topology on the tectal surface, induced by the anatomy of the retino-tectal connections. Our analysis predicts the experimentally observed "near-neighbour" relationships between points in the visual field and their representation in the tectum. Further, in this context, topological arguments are presented to indicate that if the normal developing retinal disc in goldfish undergoes a process of deformation, a discontinuity is generated at the retinal surface. This discontinuity makes the differential patterns of the retinal and tectal tissues more compatible, and also enables the retina (which grows throughout the life of the animal) to conveniently connect to the tectum.

Animals↗
PubMed2006

Retinal vein thrombosis associated with pegylated-interferon and ribavirin combination therapy for chronic hepatitis C.

An estimated 300 million people worldwide suffer from chronic hepatitis C with a prevalence of 0.8%-1.0% of the general population in Canada. An increasing pool of evidence exists supporting the use of pegylated- interferon (pegIFN) and ribavirin combination therapy for hepatitis C. We report a 49-year old male of North American aboriginal descent with chronic hepatitis C (genotype 2b). Biopsy confirmed that he had cirrhosis with a 2-wk history of left eye pain and decreased visual acuity. He developed retinal vein thrombosis after 16 of 24 wk of pegIFN-alpha 2a and ribavirin combination therapy. He was urgently referred to a retinal specialist and diagnosed with non-ischemic central retinal vein occlusion of the left eye. PegIFN and ribavirin combination therapy was discontinued and HCV RNA was undetectable after 16 wk of treatment. Hematologic investigations revealed that the patient was a factor V Leiden heterozygote with mildly decreased protein C activity. Our patient had a number of hypercoagulable risk factors, including factor V Leiden heterozygosity, cirrhosis, and hepatitis C that alone would have most likely remained clinically silent. We speculate that in the setting of pegIFN treatment, these risk factors may coalesce and cause the retinal vein thrombosis.

Antiviral Agents↗