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Optical coherence tomography in the detection of retinal break and management of retinal detachment in morning glory syndrome.

PURPOSE: To determine the efficacy of optical coherence tomography (OCT) in the management of retinal detachment in morning glory syndrome (MGS). DESIGN: Prospective, interventional case series. METHODS: Five eyes of five consecutive MGS patients who developed retinal detachment between August 2000 and June 2004 were enrolled and examined by OCT at presentation of retinal detachment. Four eyes were found to have a slit-like break at the margin of the excavation by careful OCT scanning 360 degrees around the excavation. All four eyes underwent pars plana vitrectomy, gas injection and postoperative laser photocoagulation. Postoperative OCT was performed to confirm the closure of the retinal break and reattachment of the retina. RESULTS: Optical coherence tomography detected a slit-like break at the margin of excavation in four of five patients. The retina reattached in all five eyes over the subsequent 3-50-months (average 28 months) follow-up period. Postoperative OCT showed retinal break closure at the margin of the excavation. In the one eye in which no retinal break could be detected by OCT, the retina was reattached after pars plana vitrectomy and removal of gel-like tissue. CONCLUSIONS: Optical coherence tomography is beneficial in the detection of subtle slit-like breaks at the margin of excavation in retinal detachment in MGS. It provides good guidance in subsequent surgery and is very helpful in confirming the closure of the retinal break.

Adult↗

Course of diabetic retinopathy following cataract surgery.

Five patients with mild to moderate retinopathy to both eyes underwent complication-free cataract surgery in one eye. Within three months of surgery deterioration of the retinopathy was observed in the operated eye only. In four patients there was an increase of intraretinal haemorrhages and hard exudates, accompanied by clinically significant macular oedema manifested as retinal thickening and extensive fluorescein leakage from both the macular and the peripapillary capillary networks. Of these four patients one also developed retinal ischaemia, evident ophthalmoscopically by flame-shaped haemorrhages and cotton-wool spots and angiographically by areas of capillary non-perfusion. The fifth patient showed proliferation of new blood vessels and vitreous haemorrhage. Diabetic patients scheduled for cataract surgery should undergo a thorough preoperative evaluation of any existing retinopathy. Postoperatively they should be followed up at close intervals so that any progression of retinopathy can be promptly detected and considered for laser treatment.

Aged↗

The sequential development of the higher visual centers in the C.N.S. of the quail.

The development of the optic tectum and the main nuclei of the visual pathways were studied in the quail and correlated with retinal development. The lateral geniculate nuclei began to establish by the 8th day of ineubation and the optic fibre reached the optic tectum by the 10th day, a time when the retina acquired its inner segments. By the 14th day when the retina became fully development, the cytological architecture in the tectum and the appearing of the other visual nuclei were completed.

Animals↗

Internal limiting membrane removal for macular detachment in highly myopic eyes.

PURPOSE: To present a treatment option for highly myopic eyes developing retinal detachment over a posterior staphyloma. DESIGN: Interventional case report. METHODS: Pars plana vitrectomy with peeling of the internal limiting membrane and gas tamponade; no laser retinopexy. RESULTS: Retinal reattachment with marked visual improvement. CONCLUSIONS: It appears that the rigid internal limiting membrane is responsible for the retina's inability to conform to the posterior staphyloma. Intraoperative findings suggest that this rigidity may also play a role in subsequent macular hole development. Internal limiting membrane removal should be considered in eyes with retinal detachment over a posterior staphyloma, whether or not a macular hole is present.

Aged↗

Hypoplasia of the optic nerve.

Premorbid ophthalmoscopic and histopathologic findings were correlated in a case of bilateral optic nerve hypoplasia in a 9-month-old infant with bilateral hydranencephaly. The double-ring sign was due to an extension of retina and retinal pigment epithelium (RPE) over the outer portion of the lamina cribrosa. The outer ring was the junction between sclera and lamina cribrosa, and the inner ring was the termination of the RPE. The center of the inner ring was the hypoplastic nerve head, which appeared whitish because of fibroglial tissue surrounding the central retinal vessels where they entered the optic nerve head. We speculate that an in utero vascular insult, after the third month of development, led to cystic cavitation of the anterior cerebral hemispheres, with subsequent retrograde degeneration of developing retinal ganglion cells.

Abnormalities, Multiple↗

Acquired immunodeficiency syndrome-related primary intraocular lymphoma.

A 37-year-old man with acquired immunodeficiency syndrome and cytomegalovirus retinitis developed primary intraocular and central nervous system lymphoma. Intraocular involvement was documented before death with vitrectomy. Autopsy demonstrated the presence of cytomegalovirus retinitis in the right eye and lymphoma in both eyes and the brain. We believe this is the first report of autopsy-confirmed primary intraocular lymphoma in a patient with the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Dysplastic canine retinal morphogenesis.

Retinal dysplasia is a failure in normal retinal development. The morphologic sequence of the dysplastic processes was examined in fetuses and neonates from dogs affected with an inherited form of retinal dysplasia. The dysplastic change has its onset at 45-50 days' gestation and is most prominent in the dorsal peripapillary retina. Morphologic characteristics of involved sensory retina include the focal loss of cell junctions forming the external limiting membrane, folding of the sensory retina, disorganized proliferation of neuroblasts in the retina and subretinal space, and formation of rosettes composed of multiple layers of neuroblasts. These morphologic changes suggest that there is an intrinsic abnormality of neural retinal differentiation.

Animals↗

Chronic retinitis in rats infected as neonates with lymphocytic choriomeningitis virus: a clinical, histopathologic, and electroretinographic study.

The long-term sequelae to infection of neonatal rats with lymphocytic choriomeningitis virus were studied by a variety of approaches, including indirect ophthalmoscopic, electroretinographic, and histopathologic methods. Data from these studies demonstrated that a progressive chronic retinitis develops after the acute, virus-specific, immune-mediated retinopathy. This chronic inflammation eventually leads to a total destruction of the retinal architecture. An autoimmune reaction against normally sequestered retinal antigens, released during the acute state of necrotizing retinitis, is probably the initiating mechanism of the chronic disease. This experimental disease, triggered by infection with a relatively harmless virus, constitutes a very convenient animal model of chronic retinitis.

Animals↗

Analysis of a distinctive protein in chick retina during development.

Soluble proteins from the chick retina were analyzed at various developmental stages by SDS-polyacrylamide gel electrophoresis. A peptide of about 24,000 daltons (24 Kd protein) appeared in the 14-day embryo and gradually increased with embryonic age, maintaining a fairly steady level after hatching. Polypeptides which correspond to actin and tubulin, however, remained almost unchanged during development. The 24 Kd protein was not detected in the cerebrum, tectum, pigment epithelium or vitreous body at any age. To characterize this protein, it was partially purified by gel filtration and ion exchange column chromatography, and its isoelectric point was measured. It was focused in a diffuse spot at about pH 5.5. In the bovine retina, a protein was observed at 24,000 daltons on SDS-polyacrylamide gel, but its isoelectric point was more basic than that of chick retina. It is suggested that the 24 Kd protein is one of the distinctive proteins that increase in concentration during the chick retinal development, and would be closely associated with retinal functions.

Animals↗

Properties of K+ conductances in cat retinal ganglion cells during the period of activity-mediated refinements in retinofugal pathways.

During ontogeny retinal ganglion cells manifest pronounced changes in excitable membrane properties. To further our understanding of the ionic conductances underlying such functional changes, the whole-cell voltage-clamp variation of the patch-clamp technique was used to record potassium currents in 220 ganglion cells dissociated from cat retinas ranging in age from embryonic day 31 to postnatal day 10. Potassium currents were isolated by blocking voltage-gated Na+ and Ca2+ currents with tetrodoxin (TTX) and CoCl2 respectively and were characterized by their pharmacology, kinetics and voltage-dependence of activation and inactivation. In all cases, a combination of three currents accounted for the total outward calcium-independent K+ current: (i) a steady linear conductance; (ii) a voltage-gated transient current, IA, and (iii) a voltage-gated sustained current, IK. Both voltage-gated currents were affected by the application of 4-aminopyridine and tetraethylammonia (TEA): IA showed a greater sensitivity to 4-aminopyridine, while IK was more sensitive to TEA. Both voltage-gated currents were present throughout the developmental period examined; however, the percentage of retinal ganglion cells (RGCs) expressing IA showed a marked decline from 82% at E31 to 45% at postnatal ages. During this developmental period there was an increase in the density of the two voltage-gated and the linear conductance. Additionally, with maturation, significantly slower inactivation kinetics were observed for IK. These findings, and our previous results dealing with maturational changes in the TTX-sensitive voltage-gated Na current, are related to the generation of excitability in developing retinal ganglion cells. Furthermore, the presence of cells with and without transient K+ conductance throughout development suggests that the different spiking patterns observed in RGC classes may be partially due to differences in their membrane properties.

Aging↗

Naturally occurring cell death and migration of microglial precursors in the quail retina during normal development.

We compared chronotopographical patterns of distribution of naturally occurring neuronal death in the ganglion cell layer (GCL) and the inner nuclear layer (INL) with patterns of tangential and radial migration of microglial precursors during quail retinal development. Apoptotic cells were identified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling technique, and microglial precursors were identified by immunocytochemistry with an antibody recognizing quail microglial cells (QH1 antibody). Apoptotic cells were first detectable in the GCL at the seventh day of incubation (E7), were most abundant at E10, and were absent after E13. In the INL, apoptotic cells first appeared at E7, were most abundant at E12, and disappeared entirely after the third posthatching day (P3). In both retinal layers, cell death first appeared in a small central area of the retina and subsequently spread along three gradients: central-to-peripheral, temporal-to-nasal, and dorsal-to-ventral. The chronology of tangential (between E7 and E16) and radial migration (between E8 and P3) of microglial precursors was highly coincident with that of cell death in the GCL and INL. Comparison of the chronotopographical pattern of distribution of apoptotic nuclei in the GCL with the patterns of tangential and radial migration of microglial precursors neither supported nor refuted the hypothesis that ganglion cell death is the stimulus that triggers the entry and migration of microglial precursors in the developing retina. However, microglial cells in most of the retina traversed the INL only after cell death had ceased in this layer, suggesting that cell death in the INL does not attract microglial precursors migrating radially. Dead cell debris in this layer was phagocytosed by Müller cells, whereas migrating microglial cells were seen phagocytosing apoptotic bodies in the nerve fiber layer and GCL but not in the INL.

Aging↗

A critical role of the strychnine-sensitive glycinergic system in spontaneous retinal waves of the developing rabbit.

In the developing vertebrate retina, spontaneous electric activity occurs rhythmically in the form of propagating waves and is believed to play a critical role in activity-dependent visual system development, including the establishment of precise retinal and geniculate circuitry. To elucidate how spontaneous retinal waves encode specific developmental cues at various developmental stages, it is necessary to understand how the waves are generated and regulated. Using Ca(2+) imaging and patch clamp in a flat-mount perinatal rabbit retinal preparation, this study demonstrates that, in addition to the cholinergic system, a strychnine-sensitive system in the inner retina plays an obligatory and developmentally regulated role in the initiation and propagation of spontaneous retinal waves. This system, which is believed to be the glycinergic network, provided an excitatory drive during early retinal development. It then became inhibitory after postnatal day 1 (P1) to P2, an age when a number of coordinated transitions in neurotransmitter systems occurred concomitantly, and finally contributed to the complete inhibition and disappearance of spontaneous waves after P7-P9. This glycinergic contribution was notably distinct from that of the ionotropic GABAergic system, which was found to exert an inhibitory but nonessential influence on the early wave formation. Blocking glycine- and GABA-gated anion currents had opposing effects on spontaneous retinal waves between embryonic day 29 and P0, suggesting that Cl(-) transporters, particularly R(+)-butylindazone-sensitive K-Cl cotransporters, may have a synapse- and/or cell type-specific distribution pattern, in addition to an age-dependent expression pattern in the inner retina. Overall, the results revealed an important reliance of spontaneous retinal waves on dynamic and coordinated interactions among multiple, nonredundant neurotransmitter systems.

Aging↗

Branch vein occlusion. Retinal neovascularization outside the involved segment.

Three hundred sixty-six cases of branch vein occlusion entered within the multicenter Branch Vein Occlusion Randomized Clinical Trial have been reviewed. Four cases that developed retinal neovascularization outside of the retinal area involved with the occlusion have been documented by photography and fluorescein angiography.

Aged↗

Spatial organization of retinal information about the direction of image motion.

The visual stimuli that elicit neural activity differ for different retinal ganglion cells and these cells have been categorized by the visual information that they transmit. If specific visual information is conveyed exclusively or primarily by a particular set of ganglion cells, one might expect the cells to be organized spatially so that their sampling of information from the visual field is complete but not redundant. In other words, the laterally spreading dendrites of the ganglion cells should completely cover the retinal plane without gaps or significant overlap. The first evidence for this sort of arrangement, which has been called a tiling or tessellation, was for the two types of "alpha" ganglion cells in cat retina. Other reports of tiling by ganglion cells have been made subsequently. We have found evidence of a particularly rigorous tiling for the four types of ganglion cells in rabbit retina that convey information about the direction of retinal image motion (the ON-OFF direction-selective cells). Although individual cells in the four groups are morphologically indistinguishable, they are organized as four overlaid tilings, each tiling consisting of like-type cells that respond preferentially to a particular direction of retinal image motion. These observations lend support to the hypothesis that tiling is a general feature of the organization of information outflow from the retina and clearly implicate mechanisms for recognition of like-type cells and establishment of mutually acceptable territories during retinal development.

Animals↗

Retinal patterning in the zebrafish mutant cyclops.

Determination of cell fate in the vertebrate retina has been shown to be largely independent of lineage. After cell fates are determined, retinal neurons become organized in a precise laminar pattern. The mechanisms for this patterning could involve morphogens distributed in gradients or, alternatively, direct cell-cell interactions. In the zebrafish mutant cyclops (Cyc(b16)), most embryos have two partial retinas joined in the ventral midline. This presents developing retinal cells near the midline with abnormal cellular environments, whereas laterally the pattern of developing cells is normal. We examined the consequences of this for patterning in the mutant's retina. We found that the retinas are joined in the midline at the apical surfaces of the photoreceptor layers. A laminar pattern emerges in the midline that preserves normal positional relationships between retinal cell types locally but is abnormal with respect to patterning over the entire retina. Lateral to the midline, retinal patterning appears normal. Metabolic labeling experiments showed that late rounds of DNA synthesis precede the emergence of the novel pattern in this midline region. We conclude that these observations in the cyclops mutant are compatible with mechanisms of pattern formation in the retina involving local cell interactions.

Animals↗

Histogenesis of the retina in murine trisomy 19.

Retinal development of trisomy 19 (Ts19) mice has been studied by microscopy from postnatal day 2 (PD 2) to PD 15. Gross malformations of the eye or alterations of the cellular arrangement are not detectable; retinal differentiation follows the regular pattern observed in chromosomally balanced control littermates. At all stages examined, the development of the retina in Ts19 lags approximately 2 days behind littermate controls. The maturation of all cellular constituents examined is retarded to the same degree. Appearance of the outer plexiform layer, cessation of mitotic activity, penetration of blood vessels in the nerve fiber layer and in the outer plexiform layer, differentiation of the inner granular layer and receptor formation are each delayed about two days. On a cellular level, there is no indication for an asynchronous development in the retina of Ts19. In addition to the retarded maturation, the diameters of the eyes are reduced in Ts19 mice.

Animals↗

Nitric oxide regulates the proliferation of chick embryo retina cells by a cyclic GMP-independent mechanism.

Nitric oxide (NO) is an intercellular messenger involved in many physiological and pathological processes of vertebrate and invertebrate animal tissues. In the embryonic chick retina, nitric oxide synthase (NOS) activity and a system for l-arginine transport between neurons and glial cells were described, supporting the idea that nitric oxide is a critical molecule during retinal development. In the present work we show that nitric oxide is a modulator of cell proliferation in chick embryo retina. Mixed cultures of retinal neurons and glial cells were submitted to [(3)H]-thymidine incorporation after drug treatment. Incubation for 24h with the NO donors S-nitroso-N-acetyl-penicillamine (SNAP) or Spermine nitric oxide (SpNO) complex promoted a decrease of approximately 70% of [(3)H]-thymidine incorporation in a dose-dependent manner. SNAP did not increase Lactate dehydrogenase release and its effect was not mimicked by 8-bromo cyclic GMP, or blocked by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), indicating that the effect was not due to cell death or mediated by increases of cyclic GMP levels. The inhibition was completely prevented by dithiotreitol (DTT), strongly indicating the participation of an S-nitrosylation mechanism. SNAP blocked the increase of [(3)H]-thymidine incorporation induced by ATP. Using purified cultures of glial cells we showed that the NO donor SNAP produced an inhibition of 50% in cell proliferation and did stimulate ERK1/2 phosphorylation, indicating that the inhibition of this pathway was not involved in its cytostatic effect. [(3)H]-Thymidine autoradiography of mixed cultures showed labeling of oval nuclei of glial flat cells. The injection of eggs with SNAP also did promote an intense inhibition of [(3)H]-thymidine incorporation in retinas from 9-day-old embryos. These data suggest that nitric oxide affects the proliferation of chick embryo retina glial cells in culture or "in vivo" through cyclic GMP and ERK-independent pathways.

Animals↗

Vax genes ventralize the embryonic eye.

The vertebrate retina and optic nerve are strikingly different in terms of their size, organization, and cellular diversity, yet these two structures develop from the same embryonic neuroepithelium. Precursor cells in the most ventral domain of this epithelium give rise only to the astrocytes of the optic nerve, whereas immediately adjacent, more dorsal precursors give rise to the myriad cell types of the retina. We provide genetic evidence that two closely related, ventrally expressed homeodomain proteins-Vax1 and Vax2-control this neuroepithelial segregation. In the absence of both proteins, we find that the optic nerve is transformed in its entirety into fully differentiated retina. We demonstrate that this transformation results from the loss of ventralizing activity in the developing eye field, and that ventralization is mediated, at least in part, via Vax repression of the Pax6 gene, a potent inducer of retinal development.

Animals↗