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PubMed1985

Bilateral macular dysplasia ('colobomata') and congenital retinal dystrophy.

Three unrelated patients with bilateral macular dysplasia ('colobomata') with no relevant family history were found to have absent or substantially abnormal electroretinograms, implying that there was an associated retinal dystrophy. This may suggest that the macular lesions are associated with a global failure of retinal development, with a regional preponderance rather than a purely localised cause such as an intrauterine infection. It is important to distinguish between congenital infections such as toxoplasmosis and developmental macular colobomata, which have a somewhat similar ophthalmoscopic appearance as a cause of bilateral macular abnormalities seen in young children, since they have different implications for genetic advice and future ophthalmic care.

Adolescent↗
PubMed2002

A comparison of laser photocoagulation with cryotherapy for threshold retinopathy of prematurity at 10 years: part 1. Visual function and structural outcome.

OBJECTIVE: To assess visual and structural outcomes after laser photocoagulation and transscleral cryotherapy for threshold retinopathy of prematurity (ROP) after 10 years. DESIGN: Extended follow-up of a randomized controlled clinical trial. PARTICIPANTS: One hundred eighteen eyes from 66 patients were randomly assigned to receive either cryotherapy or laser photocoagulation for threshold ROP. Forty-four eyes from 25 patients were examined for 10-year follow-up evaluations. INTERVENTION: Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, slit-lamp, and fundus examination; fundus photography; and B-scans (eyes with retinal detachments) were performed. Patients' histories were taken to elicit past amblyopia therapy. Based on fundus photographs, independent observers graded the degree of retinal dragging as none, mild, moderate, or severe. MAIN AND SECONDARY OUTCOME MEASURES: Best-corrected ETDRS visual acuity (BCVA). The degree of dragging was determined clinically and photographically. In addition, the presence of strabismus or amblyopia and/or any history of treatment for amblyopia were noted accordingly. RESULTS: Eyes treated with laser had a mean BCVA of 20/66 (Snellen equivalent), whereas cryotherapy-treated eyes had a mean BCVA of 20/182 (Snellen equivalent) (P = 0.015, n = 42). Compared with eyes treated with cryotherapy, eyes treated with laser photocoagulation were 5.2 times more likely to have a 20/50 or better BCVA (95% confidence interval, 1.37-19.8, n = 42). Eyes treated with cryotherapy were 7.2 times (95% confidence interval, 1.54-33.6, n = 33) more likely to develop retinal dragging compared with laser treatment. By linear regression analysis, ETDRS visual acuity was inversely proportionate to the degree of retinal dragging in both laser (r = -0.637, P = 0.006) and cryotherapy (r = -0.517, P = 0.040) treated eyes. Among the 21 patients with favorable outcomes in both eyes, 13 had strabismus (62%) and 6 had received amblyopia therapy (29%). Ptosis, loss of cilia, and cortical cataract were among probable treatment-related complications that were noted in this study. CONCLUSIONS: Overall, laser-treated eyes had better structural and functional outcome compared with eyes treated with cryotherapy.

Child↗
PubMed1995

Mash-1 is expressed during ROD photoreceptor differentiation and binds an E-box, E(opsin)-1 in the rat opsin gene.

It has been shown previously that the transcription factor Mash-1 plays a significant role in mammalian neurogenesis. In the present study we show that Mash-1 is expressed during rat retinal development and that it interacts specifically with an E-box identified in the promoter of the opsin gene during rod photoreceptor differentiation. We propose that opsin may be one of the downstream neuronal genes regulated by Mash-1 during neurogenesis in the central nervous system.

Animals↗
PubMed1985

Taurine: its biological role and clinical implications.

More than simply cataloging the numerous experimental models in which taurine plays a modulating role, this discussion aims at stimulating further investigation of the potential clinical value of this abundant sulfur amino acid. Both the biomedical investigator and clinician must be struck by the enormous amount of taurine floating freely in the intracellular water of the cells. In cardiac tissue alone, taurine levels of 20 mM or higher may be found. Given this abundance of taurine, why is our understanding of its function so elusive? Although it is clear taurine is important in conjugating bile acids to form water-soluble bile salts, only a fraction of available taurine is used for this function, predominantly in young animals and children. While taurine conjugation is the preferred route of bile acid conjugation in the young, changes in adults given 250 mg of taurine daily for two to three weeks are insignificant. Total pool size of bile acid and chenodeoxycholic acid declines. Unchanged are the rate of bile acid synthesis or the secretion rates of biliary cholesterol, bile acid and phospholipids. Biliary cholesterol saturation also stays the same. The finding that taurine availability protects against cholestasis induced by monohydroxy bile acids remains confined to guinea pigs. The abundance of taurine suggests it may be an osmoregulator of cell volume, and there is convincing evidence that it serves this function in fish. Taurine may play this role in the brain under high osmotic states such as hypernatremia, dehydration and uremia. Evidence is strong that taurine is vital in maintaining retinal function, which may explain why taurine is so abundant in human breast milk. Prolonged TPN feeding of infants demonstrates the importance of taurine in retinal development. We have begun to appreciate the role of the kidney in conserving taurine and how this is perturbed in the neonatal period. Taurine has recently been added to infant formulas (about 50 mg/L). Cataloging what we know of taurine function, however, produces a list of "maybes." Now is the time for exhaustive, careful taurine research that will produce more definite answers.

Animals↗
PubMed1986

[Bilateral cytomegalovirus retinitis in an infant with fatal congenital AIDS].

The authors report on a baby born on August 25, 1984 with a birthweight of 1100 g. Her parents used drugs intravenously and her mother had anti-HTLV III antibody. In the clinical course an immune deficiency syndrome with pathologic reduction of T4:T8 (T-helper: T-suppressor cells) was apparent. The child had no anti-HTLV III antibody, but exposition, typical clinical course and immunological data led to the diagnosis Acquired Immune Deficiency Syndrome (AIDS). In the 9th month bilateral progressive retinitis developed; it was thought to have been induced by cytomegalovirus. Complement-fixation antibody titer for cytomegalovirus was negative, but the virus was found in the urine. In the 12th month the baby died of cardiac arrhythmia caused by cytomegalic myocarditis. Macroscopic and light-microscopic illustrations of the inflammatory changes in both eyes are presented; in the retina there were large multinucleated cells which were visible macroscopically.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Changes in retinal structure during development and settlement of the goatfish Upeneus tragula.

The retinal structure of the goatfish Upeneus tragula was examined at various stages of the fish's development from pre-settlement pelagic larvae to benthic juveniles. Histological investigation revealed a double layer of cone inner segments in the dorsal retina and high cone and bipolar cell densities in both dorsal and ventral retina prior to settlement. During settlement reorganisation of the dorsal retina was found to occur, with the two cone layers slotting together to form a single layer. In both the dorsal and ventral retina cone and bipolar cell densities were rapidly reduced. Visual acuity, as calculated from histological data on cone density and lens diameter, was found to increase rapidly prior to settlement to an asymptote of approximately 27 minutes of arc, which corresponded to settlement. The changes in the visual system are thought to be associated with changes in both habitat and feeding behaviour at settlement when the fish leave the surface waters and begin a benthic mode of life using sensory barbels to search for sediment dwelling prey.

Animals↗
PubMed1991

GABA-like immunoreactivity in the developing chick retina: differentiation of GABAergic horizontal cell and its possible contacts with photoreceptors.

The morphology of gamma-aminobutyric acid (GABA)-containing horizontal cells was examined in mature and developing chick retinas by GABA immunocytochemistry. In the outer plexiform layer of the mature retina, GABA-immunoreactive components were located in three different sublayers. In the inner (vitreal) layer most positively-stained fibres were laterally oriented processes from horizontal cells. Thick processes were found in the middle layer, and the relatively thin fibres in the outer (scleral) layer showed a concave curvature, suggesting their termination on photoreceptor terminals. By electron microscopy it was found that the principal cone pedicles were usually indented by immunoreactive lateral neurites of horizontal cells but that rod spherules faced only occasionally immunoreactive fibres. Accessory cones and single cones were also not usually indented by immunoreactive fibres. These observations may indicate that horizontal cells regulate the excitation of cone photoreceptors by several different inhibitory mechanisms. During retinal development, horizontal cells begin to extend lateral fibres by the ninth embryonic day, and some GABAergic horizontal cells also possess inwardly extending fibres until embryonic day 11. Between embryonic days 13 and 15, some immunoreactive cells were found among the bipolar cells, suggesting that they were still migrating to their final position. On embryonic day 17, the staining pattern was very similar to that of the mature retina. These results suggest that GABA immunohistochemistry may be an excellent tool for studying horizontal cell differentiation.

Animals↗
PubMed2000

Spatiotemporal expression patterns of 6B4 proteoglycan/phosphacan in the developing rat retina.

PURPOSE: To investigate expression of 6B4 proteoglycan/phosphacan, the major constituent of chondroitin sulfate proteoglycan and a possible modulator of neural network formation in the developing central nervous system, in developing rat retina. METHODS: Changes in expression and localization of 6B4 proteoglycan in developing rat retina were investigated by reverse transcription-initiated polymerase chain reaction (RT-PCR), immunohistochemistry, and immunoblot analysis. RESULTS: Semiquantitative RT-PCR revealed that mRNA expression of 6B4 proteoglycan in retinas peaked at postnatal day 14 (P14) and then decreased at P42. Immunohistochemical analyses using MAb 6B4, a monoclonal antibody against 6B4 proteoglycan, revealed faint immunoreactivity in the inner aspects of the retina at embryonal day 16 (E16). At birth, weak immunoreactivity was present in the nerve fiber layer (NFL) and inner plexiform layer (IPL). At P7 and P14, the NFL, IPL, and outer plexiform layer (OPL) stained intensely, but the ganglion cell layer (GCL) remained unstained. Between P21 and P42, immunoreactivity in the NFL and IPL weakened slightly. Immunoblot analyses showed a MAb 6B4 immunopositive band in the retinal soluble fraction treated with chondroitinase ABC. The amount of the immunopositive band increased rapidly as retinal development proceeded. Surprisingly, a significant amount of the immunopositive band was present in the retina even before digestion with chondroitinase ABC, indicating that at least part of 6B4 proteoglycan in rat retina exists in a non-proteoglycan form. CONCLUSIONS: The existence of 6B4 proteoglycan/phosphacan was thus demonstrated in rat retina, although some biochemical parameters were different from those of the 6B4 proteoglycan seen in brain.

Animals↗
PubMed2004

Developmental plasticity of photoreceptors.

During development, retinal ganglion cells undergo conspicuous structural remodeling as they gradually attain their mature morphology and connectivity. Alterations in their dendritic organization and in their axonal projections can also be achieved following early insult to their targets or their afferents. Other retinal cell types are thought not to display this same degree of developmental plasticity. The present review will consider the evidence, drawn largely from recent experimental studies in the carnivore retina, that photoreceptors also undergo structural remodeling, extending their terminals transiently into inner plexiform layer before retracting to the outer plexiform layer. The determinants of this transient targeting to the inner plexiform layer are considered, and the role of cholinergic amacrine cells is discussed. The factors triggering this retraction are also considered, including the concurrent maturational changes in outer segment formation and in the differentiation of the outer plexiform layer. These results provide new insight into the life history of the photoreceptor cell and its connectivity, and suggest a transient role for the photoreceptors in the circuitry of the inner retina during early development, prior to the onset of phototransduction.

Aging↗
PubMed1996

Reorganization of membrane contacts prior to apoptosis in the Drosophila retina: the role of the IrreC-rst protein.

The final step of pattern formation in the developing retina of Drosophila is the elimination of excess cells between ommatidia and the differentiation of the remaining cells into secondary and tertiary pigment cells. Temporally and spatially highly regulated expression of the irregular chiasmC-roughest protein, an adhesion molecule of the immunoglobulin superfamily known to be involved in axonal pathfinding, is essential for correct sorting of cell-cell contacts in the pupal retina without which the ensuing wave of apoptosis does not occur. Irregular chiasmC-roughest accumulates strongly at the borders between primary pigment and interommatidial cells. Mutant and misexpression analysis show that this accumulation of the irregular chiasmC-roughest protein is necessary for aligning interommatidial cells in a single row. This reorganisation is a prerequisite for the identification of death candidates. Irregular chiasmC-roughest function in retinal development demonstrates the importance of specific cell contacts for assignment of the apoptotic fate.

Animals↗
PubMed2002

Cataract extraction in high myopic eyes.

BACKGROUND: According to the high prevalence of myopia in Taiwan, we analyze the adopted cataract extractions, identify predicting factors for postoperative vision, and to assess the incidence of retinal complications after Nd: YAG laser capsulotomy in high myopic eyes. METHODS: One hundred and twenty-five eyes, which the axial lengths were longer than 26 mm, following cataract extraction were enrolled. Surgeries adopted included phacoemulsification with intraocular lens implantation, extracapsular cataract extraction with intraocular lens implantation, phacoemulsification, and extracapsular cataract extraction. Logistic regression was utilized to assess predictive factors for postoperative vision. RESULTS: Postoperative vision of 41 eyes (32.8%) of the 125 high myopic eyes improved at least 4 lines of Snellen acuity. Thirty-two eyes (25.6%) achieved good postoperative vision (BCVA > or = 20/40), and 26 eyes (20.8%) demonstrated poor postoperative vision (BCVA < 20/200). Younger age and shorter axial length were appreciated for better visual outcome (p < 0.05). Nd: YAG laser capsulotomy is required for posterior capsular opacity. Three in 125 eyes (2.4%) developed retinal complications and 2 of them had retinal detachment subsequently within one month after Nd: YAG laser capsulotomy. CONCLUSION: Most high myopic patients achieved visual improvement after cataract surgeries. Age and axial length are the predictive factors in high myopic patients. It is crucial to examine retina prior to Nd: YAG laser capsulotomy to prevent retinal complication.

Adult↗
PubMed1996

Development of retino-tectal arborizations in the trout.

In order to visualize the organization and the morphology of developing retinal axons in the trout (Oncorhynchus mykiss), HRP or DiI crystals were applied on the central part of the retina at different stages ranging from 21 days postfertilization (stage 27) to one month post-hatching (stage 36). Retinal axons and arborizations were observed on tectal whole mounts with a light microscope. The earliest stage investigated (stage 27) showed two groups of axons entering the tectum by its ventro-rostral part and extending in a dorso-caudal direction. As the tectum grows, these two groups separate to outline the dorsal and the ventral borders of the tectum. At three weeks post-hatching (stage 35) we observed three distinct brachia: the dorsal and ventral fascicles, and a small group in the middle that we called the intermediate fascicle. At hatching (stage 30), retinal axons start to arborize in the centre of the tectum. During the first month post-hatching, these axons migrate dorso-caudally and exhibit various morphologies. Until two weeks post-hatching (stage 34), they sprout a few long side branches, bearing numerous filopodial growth cones, in a phase of exploratory growth towards their target site. At stage 36, four types of terminal arborizations can be identified on the basis of their tangential and radial location in the tectum, and on their gross morphology. Three of these arbor types are already present at earlier stages and undergo refinements in their shape--reduction in their branching axes, loss of branches that are behind the terminal arborization, and the sprouting of more numerous branches at their extremities. These findings confirm that the widely branched arborizations are transient during development.

Age Factors↗
PubMed2004

Cloning of chicken choline acetyltransferase and its expression in early embryonic retina.

The enzyme choline acetyltransferase [EC 2.3.1.6] (ChAT) synthesizes the neurotransmitter acetylcholine that plays a key morphogenic role in vertebrate retina development. As the embryonic avian retina is particularly useful for morphogenetic studies, we cloned the complete coding region of chicken ChAT cDNA. At the deduced amino acid level, chicken ChAT is approximately 76% identical to mammalian ChAT proteins. We also report here the cloning of the complete 5' end of the complex cholinergic locus. This locus contains both the ChAT gene and the nested intronless gene for the vesicular acetylcholine transporter (VAChT). The genomic organization of the 5' end of the chicken cholinergic locus is similar to that reported in other vertebrate species. A 5.7 kb mRNA corresponding to the ChAT message was detected in both embryonic retina and post-hatch brain. An analysis of the ChAT mRNA in embryonic chick retina shows that the message can be detected by E6 and its level increased during early retinal development. Vertebrate ChAT mRNAs can contain one or more of three non-coding exons, M, N or R and by RT-PCR we demonstrate, at least, a chicken ChAT mRNA containing exon M.

Amino Acid Sequence↗
PubMed2001

Evidence for two distinct mechanisms of neurogenesis and cellular pattern formation in regenerated goldfish retinas.

After its destruction by intraocular injection of ouabain, the goldfish retina regenerates, but little is known about the histogenesis of the new tissue, including the structure and formation of regenerated cell mosaic patterns. In an effort to determine how retinal cells are generated and spatially organized within retina regenerated after ouabain injection, in situ hybridization and immunocytochemical techniques were combined with computational analyses of two-dimensional spatial patterns of identified neurons. Labeling with specific opsin riboprobes revealed two distinct cone patterns in the ouabain-injected eyes, each of which was different from the relatively orderly cone patterns of native retina. Central, regenerated regions had sparse aggregates of cones, and a relatively lower density of each cone type. Peripheral regions of experimental retina, likely derived from the circumferential germinal zone, had high densities of all cone types, each of which tended to be distributed randomly. The spatial patterns of inner retinal neurons in experimental eyes were also disorganized with respect to native retina. These results indicate that although some aspects of retinal regeneration resemble normal retinal development and growth, ouabain-induced regeneration does not produce well-organized mosaics of neurons, indicating a failure of the developmental interactions needed for proper pattern formation, which in turn could compromise visual recovery. Furthermore, the distinct cone patterns in different regions of experimental retina support the hypothesis that new goldfish retina arises via two spatially and cellularly distinct mechanisms after exposure to ouabain.

Animals↗
PubMed1998

Interaction of calcium-permeable non-N-methyl-D-aspartate receptor channels with voltage-activated potassium and calcium currents in rat retinal ganglion cells in vitro.

Calcium-permeable non-N-methyl-D-aspartate receptor channels are now characterized in much detail, but still little is known about the consequences of Ca2+ influx through these channels in specific neuron types. We are interested in the role of Ca2+-permeable non-N-methyl-D-aspartate receptor channels during differentiation of retinal ganglion cells. However, in view of the conflicting data on the relative Ca2+ permeability of non-N-methyl-D-aspartate receptor channels in these neurons, a more systematic evaluation of permeation properties of different Na+ substitutes was necessary before proceeding with the main goal of the present study evaluating the effects of non-N-methyl-D-aspartate receptor activation on repetitive firing and voltage-activated K+ and Ca2+ conductances. Retinal ganglion cells were dissociated from the rat retina on postnatal day 5. They were selected by vital anti-Thy-1 immunostaining and repetitive firing behaviour and submitted to patch-clamp recording in the whole-cell configuration. Non-N-methyl-D-aspartate receptor channels were activated by application of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate. It was found that they were essentially impermeable to N-methyl-D-glucamine (P(NMDG)/P(Cs)<0.02), but not to choline (P(choline)/P(Cs)=0.24) and tetramethylammonium (P(TMA)/P(Cs)=0.23). When using N-methyl-D-glucamine as a substitute for Na+ to obtain bi-ionic conditions P(Ca)/P(Cs) varied between 0.08 to 1.40. Linear current voltage relation or little outward rectification corresponded to a low Ca2+ permeability (P(Ca)/P(Cs)=0.14). In about one third of the cells kainate-induced currents showed inward rectification and non-N-methyl-D-aspartate receptor agonists induced a substantially higher Ca2+ influx (P(Ca)/P(Cs)=0.64). Activation of non-N-methyl-D-aspartate receptors by kainate profoundly altered the repetitive discharge of retinal ganglion cells. In contrast to the continuously firing controls, cells generated only a few spikes at the beginning of a steady depolarization after kainate exposure. Among the candidates regulating the firing behaviour of retinal ganglion cells voltage-activated Ca2+ and K+ conductances were tested for their sensitivity to kainate application. It was found that even short conditioning pulses of kainate decreased the peak amplitudes of both voltage-activated K+ and voltage-activated Ca2+ currents. Only the latter effect required extracellular Ca2+ and was antagonized by increasing the intracellular Ca2+ buffering strength. Thus, suppression of calcium currents was induced by a non-N-methyl-D-aspartate receptor-mediated rise of the intracellular calcium concentration. The reduction of K+ currents did not depend on extracellular calcium and was insensitive to experimental manipulation of intracellular Ca2+ buffer strength. The interaction between Ca2+-permeable non-N-methyl-D-aspartate receptor channels and voltage-activated Ca2+ and K+ currents may represent an important regulatory mechanism to control the repetitive firing of developing retinal ganglion cells.

Animals↗
PubMed2005

Functional maturation of the macaque's lateral geniculate nucleus.

Vision in infant primates is poor, but it is not known which structures in the eye or brain set the main limits to its development. We studied the visual response properties of 348 neurons recorded in the lateral geniculate nucleus (LGN) of macaque monkeys aged 1 week to adult. We measured spatial and temporal frequency tuning curves and contrast responses with drifting achromatic sinusoidal gratings. Even in animals as young as 1 week, the main visual response properties of neurons in the magnocellular (M) and parvocellular (P) divisions of the LGN were qualitatively normal, including the spatial organization of receptive fields and the characteristic response properties that differentiate M- and P-cells. At 1 and 4 weeks, spatial and temporal resolution were less than one-half of adult values, whereas contrast gain and peak response rates for optimal stimuli were about two-thirds of adult values. Adult levels were reached by 24 weeks. Analysis of correlations between S-potentials representing retinal inputs and LGN cells suggested that the LGN follows retinal input as faithfully in infants as in adults, implicating retinal development as the main driving force in LGN development. Comparisons with previously published psychophysical data and ideal observer models suggest that the relatively modest changes in LGN responses during maturation impose no significant limits on visual performance. In contrast to previous studies, we conclude that these limits are set by neural development in the visual cortex, not in or peripheral to the LGN.

Age Factors↗
PubMed2003

Adenosine regulates the survival of avian retinal neurons and photoreceptors in culture.

Adenosine modulates the survival of chick embryo retinal neurons in culture. When cultures were incubated for 3 days and refed with fresh medium, a large proportion of neurons died in the subsequent 3 days of culture. This cell death was prevented by preincubation of cultures for at least 24 h with adenosine plus the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), an adenosine uptake blocker nitrobenzylthioinosine (NBI), the adenosine A2A receptor agonist 2-[4-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680), or the permeant cyclic AMP analog 8-bromo cyclic AMP, but not the A1 receptor agonist cyclohexyladenosine (CHA). Adenosine deaminase induced cell death when added to culture medium, and this effect was prevented by EHNA. Cell death was not observed when the medium was replaced by a conditioned medium from sister cultures. The data strongly suggest that adenosine regulates the survival of developing retinal neurons by a long-term activation of A2A receptors and the increase of cyclic AMP levels.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Identification of crystals in kidneys of AIDS patients treated with foscarnet.

Three acquired immune deficiency syndrome patients given foscarnet to treat cytomegalovirus retinitis developed renal failure with crystal deposits within the renal glomeruli. We identified these crystals as a mixture of sodium salt, calcium salt, and a mixed salt containing both sodium and calcium ions. This composition has not been previously reported. Foscarnet can complex available ionized calcium and secondarily precipitate in glomeruli. The percentage of complexing depends on calcium concentration in serum and the poor calcium salt solubility.

AIDS-Related Opportunistic Infections↗