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[Development of traumatic retinal detachment].

Post-traumatic retinal detachment occurs frequently as a late consequence of progressive vitreous changes, especially following penetrating injuries. Occasionally, it develops soon after the trauma, without preceding proliferative vitreoretinopathy, is based on posterior vitreous detachment and morphologically resembles an idiopathic retinal detachment. It is possible that the posterior vitreous detachment in these cases is encouraged by the presence of intravitreal hemorrhage.

Adolescent↗

Voltage-dependent sodium channels develop in rat retinal pigment epithelium cells in culture.

Whole-cell patch-clamp recordings were made from isolated cells of the retinal pigment epithelium (RPE) of neonatal rats. After 24 hr in cell culture, RPE cells developed a transient, voltage-activated inward current that was never observed in acutely isolated cells. The kinetics, voltage-dependence, and reversal potential of the current and its dependence on external sodium demonstrated that the current was due to the expression of voltage-activated Na+ channels in cultured RPE cells. The current was partly blocked by tetrodotoxin at low concentrations (< 100 nM), but a second component of Na+ current was unblocked by tetrodotoxin at concentrations up to 10 microM. Na+ channels were present in cultured RPE cells at sufficient density to support regenerative action potentials in voltage recordings. Both the epithelial cells of the RPE and the neurons of the retina derive embryonically from neural origin, and it is known that under certain circumstances, nonmammalian RPE cells retain the ability to take on neuronal characteristics. The development of voltage-activated Na+ channels and the presence of action potentials demonstrate that neonatal mammalian RPE cells are also capable of expressing neuronal characteristics in cell culture.

Animals↗

Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease.

Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal rat, vascular pruning began centrally and extended peripherally, leaving behind a less dense, smaller-caliber vasculature. The pruning was correlated with retinal vascular expression of intercellular adhesion molecule-1 (ICAM-1) and coincided with an outward-moving wave of adherent leukocytes composed in part of cytotoxic T lymphocytes. The leukocytes adhered to the vasculature through CD18 and remodeled it through Fas ligand (FasL)-mediated endothelial cell apoptosis. In a model of oxygen-induced ischemic retinopathy, this process was exaggerated. Leukocytes used CD18 and FasL to obliterate the retinal vasculature, leaving behind large areas of ischemic retina. In vitro, T lymphocytes isolated from oxygen-exposed neonates induced a FasL-mediated apoptosis of hyperoxygenated endothelial cells. Targeting these pathways may prove useful in the treatment of retinal ischemia, a leading cause of vision loss and blindness.

Animals↗

[Electron microscopic and morphometric research on the development of the outer segments of the photoreceptor cells in mutant Campbell rats with hereditary retinal dystrophy].

Development of rod outer segment (ROS) in the posterior area of the retina in normal (GR) and mutant Campbell rats with inherited retinal dystrophy was studied using transmission electron microscopy and morphometry. In both strains of rats primitive cilia appear first after birth and their number progressively increases up to postnatal day 9. The first ROS membrane disks (MD) appear at postnatal day 5. Originally MD are randomly oriented but later they acquire a regular arrangement. At day 7 MD occupy about 14% area of posterior retina in transverse sections in Campbell rats versus 7% in normal animals. By day 9 MD occupy about 35% area in the same region of the retina in both lines of rats. The retina of 15-day-old rats possesses the definitive number of differentiated ROS. The data obtained show that during the period between birth and eyelid opening ROS morphogenesis in Campbell rats is not slow or disturbed as compared with that in normal rats.

Aging↗

Cell adhesion molecules in the early developing mouse retina: retinal neurons show preferential outgrowth in vitro on L1 but not N-CAM.

Both L1 and N-CAM are present on optic axons early in the developing mouse retina and optic nerve. In in vitro assays on substrates of purified cell adhesion molecules cells derived from E13 mouse retinae showed vigorous neurite extension on L1 but not on N-CAM. Although retinal neurons on N-CAM showed only limited attachment to the substrate, they were able to form lamellipodia immediately around the cell perimeter. In contrast, similarly derived cortical cells showed extensive neurite outgrowth on both substrates. Under these culture conditions, nearly all of the L1 and N-CAM present in the cell membrane appeared to be sequestered on the lower surface of the growth cones and neurites, indicating that most of these cell adhesion molecules were involved in homophilic interactions. Our results suggest differential roles for L1 and N-CAM in initiation and establishment of the optic pathway.

Animals↗

Role of the vitreous in posterior segment neovascularization in central retinal vein occlusion.

We retrospectively studied the relationship between the vitreous condition and the development of retinal or optic disc neovascularization in 60 eyes with central retinal vein occlusion associated with extensive retinal ischemia. At initial examination, 24 of 60 eyes (40%) with central retinal vein occlusion had complete posterior vitreous detachment, a prevalence significantly higher than in the fellow eyes. During a mean follow-up period of 43 months, 13 of 34 eyes (38%) without posterior vitreous detachment developed retinal or disc neovascularization, or both, but none of the 24 eyes with complete posterior vitreous detachment developed neovascularization (P less than .001). Our results suggest that central retinal vein occlusion may induce the development of posterior vitreous detachment, and that posterior vitreous detachment may play a role in protecting eyes with central retinal vein occlusion from posterior segment neovascularization.

Adult↗

The development of non-retinal afferent projections to the frog optic tectum and the substance P immunoreactivity of tectal connections.

Accessibility in early development and the presence of a retinotopic map have made the amphibian optic tectum a popular system for exploration of the role of synaptic function in central map refinement. Although a great deal is known about the development of retinal innervation of the tectum, little information exists about the development of non-retinal tectal inputs. Since these other afferent systems may contribute to the synaptic drive of developing tectal cells and thereby be involved in the activity-dependent refinement of the retinotectal map, we sought to determine whether these inputs are present at the early tadpole stages when the first retinal axons refine their synaptic order within the tectal neuropil. Rhodamine-labelled latex beads, retrogradely transported from injection sites in the optic tecta, were used to identify tectal afferent projections. Projection patterns in very young tadpoles were identical to those found in juvenile frogs and heavily labelled regions included areas of the posteroventral tegmental field, the posterior tuberculum, the ventromedial thalamic nucleus, the ventral part of the ventrolateral thalamic nucleus, the suprachiasmatic nucleus and discrete regions within the central and anterior thalamic nuclei. Ipsilateral nucleus isthmi cells were also labelled, indicating the existence of an isthmo-tectal projection in even the youngest animals examined. Additionally, substance P-like immunoreactive tecto-isthmal fibers were traced from the optic tectum to the nucleus isthmi. The presence of these connections suggests that feedback from the nucleus isthmi and/or input from the other brain areas projecting to the tectum may play a role in modulating the cellular mechanisms that underlie the formation of the visual map.

Afferent Pathways↗

360 degrees prophylactic cryoretinopexy. A clinical and experimental study.

Complications occurred after 360 degrees prophylactic cryoretinopexy in three of six eyes in which fellow eyes had previously developed aphakic retinal detachment. Two of the six prophylactically treated eyes developed retinal detachment in advance of anticipated cataract surgery, and a third developed vitreitis and progressive preretinal membrane formation after uncomplicated cataract extraction. In an experiment study with rhesus monkeys, preretinal membrane formation was produced by administering heavy freezes with 360 degrees cryoretinopexy. Although the quantities of cold were considered excessive for clinical use, the cryoretinopexy used clinically in this series must also be considered excessive. The use of 360 degrees cryoretinopexy in the management of eyes at high risk for retinal detachment must be considered judiciously. Particular caution must be exercised in administering cryoretinopexy to nondetached retinas so as to avoid heavy freezes, which destroy the linear retinal layers.

Aged↗

Adenoviral-mediated gene transfer to retinal explants during development and degeneration.

Naturally occurring mutations of the beta subunit of the cyclic guanosine monophosphate (cGMP) phosphodiesterase (beta-PDE) gene in rod photoreceptors of mice and dogs are similar to one of the inherited retinal degenerations termed retinitis pigmentosa in humans. Defects in the rod beta-PDE gene leading to photoreceptor cell degeneration in retinal degenerative (rd) mice can be corrected by transfer of a wild type beta-PDE gene. However, the rapid photoreceptor degeneration in this mutant makes the study of gene therapy difficult. Since the retinal degeneration is slowed in vitro, we have employed retinal explants from rd mice to study factors influencing viral transduction. Retinal explants provide a rapid, efficient method to compare the transduction efficiency of adenoviral vector-mediated reporter gene delivery at different ages in normal and rd mice. Retinal explants from postnatal day (P)2 to P28 control (C57BL/6J) and P2-P42 rd mice were exposed for 20 hr to 2.5 x 10(8) plaque forming units (pfu) ml(-1) of adenoviral vector with a beta-galactosidase (Lac Z) reporter gene (Ad-CMV-Lac Z). After incubation in vector-free media for an additional 3 days, the explants were fixed and histochemically stained for beta-galactosidase to reveal Lac Z gene expression. The explants were also embedded and sectioned for light microscopic observation. Transduction efficiency was higher in rd mice than in controls on all postnatal days examined. In normal retinal explants, expression of the Lac Z gene increased from P2 to a peak around P7-P8, then decreased at subsequent ages; little transduction could be found after P17. In rd mice transduction efficiency of Ad-CMV-Lac Z increased from P2 to P7, decreased by P10 and increased again after P10. The most dramatic increase in the transduction efficiency occurred in the rd retina between P10 and P15 when Lac Z was intensely expressed throughout the retina. Microscopic examination of retinal sections revealed the types and distribution of Lac Z-positive cells responsible for the deep blue staining in the retinal whole mount. In normal and rd mice, Lac Z-positive cells were located throughout the retina. However, larger numbers of Lac Z-positive cells were present at all ages examined in retinal explants from rd mice compared to normal mice. These data indicate a difference in transduction efficiency between normal and rd mice, especially after P12, and suggest efficient adenovirus-mediated gene transfer is more attainable in developing or degenerating retina. Thus, transduction efficiency in rd mice depends on the relationship between development, maturation and the degenerative state of the photoreceptor cells.

3',5'-Cyclic-GMP Phosphodiesterases↗

Complications of pneumatic retinopexy.

Twenty-eight patients with rhegmatogenous retinal detachment were treated by pneumatic retinopexy using intravitreal perfluorpropane (C3F8) gas. Reattachment was successfully achieved in 22 eyes (78.6%) after one treatment. Most of the eyes were myopic and had a single retinal break or group of breaks within one o'clock hour. All retinal complications developed in the inferior retinal quadrants with postoperative proliferative vitreoretinopathy (PVR) as one of the most serious complications, occurring in 3 (10.7%) eyes. New retinal breaks developed in 2 (7.1%) eyes.

Adult↗

Retinal cysts in the eye of the Asian musk shrew, Suncus murinus, (Mammalia, Insectivora).

The development of retinal cysts in the eye primordia of Suncus murinus embryos was studied. Retinal infoldings were first identified in the 17.5-day-old embryo (crown rump length--CRL = 6.3 mm). At this time, the apex of the developing retinal fold could be identified attached to the lens. The pigmented epithelium did not take part in the formation of the cyst. The retinal fold closed, to form a cyst, by day 23 of embryonic development (CRL = 14.0 mm). The newly formed retinal cyst remained continuous with the retina and extended toward the lens where it attached to the lens epithelium. Retinal cysts had an oval, bilaterally symmetrical shape and a narrow lumen, which, lined by the internal limiting membrane, occasionally contained cellular debris. The dimensions of the cysts were usually 100 to 150 microns (diameter) by 200 to 250 microns (length). Retinal cysts appeared in 45 per cent of the embryos examined.

Animals↗

Differential regulation of tight junction permeability during development of the retinal pigment epithelium.

The retinal pigment epithelium (RPE) is an epithelial region of the blood-brain barrier. During embryogenesis, permeability of the barrier gradually decreases. A culture model of RPE development revealed differences in how tight junctions regulate the paracellular diffusion of ionic and nonionic solutes (Ban Y and Rizzolo LJ. Mol Vis 3: 18, 1997). To examine these differences, the permeation of ionic and nonionic monosaccharides was compared with mannitol, and the permeation of the alkali metals was compared with sodium. The order of permeation was 3-O-methlyglucose = glucosamine = mannitol > N-acetylneuraminic acid. The ratio of N-acetylneuraminic acid to mannitol permeability decreased with embryonic age of the RPE or exposure to retinal-conditioned medium. Neither the ratio nor the permeability was affected by inhibiting transcytosis. The ratio increased if tight junctions were disrupted in low-calcium medium. The permeation of cations followed the sequence cesium > rubidium > potassium = sodium > lithium and was unaffected by embryonic age or retinal-conditioned medium. These results are considered in terms of a model in which the size distribution, charge, or number of open junctional pores could be modulated. It suggests that different subpopulations of pores can be regulated independently during development.

Animals↗

Dendritic growth and remodeling of cat retinal ganglion cells during fetal and postnatal development.

We have studied the development of retinal ganglion cell morphology in the cat's visual system from early fetal to postnatal times. In particular, we have examined the contribution of growth and remodeling to the establishment of mature retinal ganglion cell form. Ganglion cells were identified by retrograde labeling with rhodamine latex microspheres deposited in the superior colliculus and lateral geniculate nucleus between embryonic day 34 (E34; birth = E65) and adulthood. To reveal the fine morphological details of retrogradely labeled ganglion cells, 48 hr later Lucifer yellow was injected intracellularly in living retinae that had been dissected and maintained in vitro. Our results show that at E35-37 the majority of ganglion cells are very simple in morphology, with a few dendritic processes that are generally aligned in a radial direction towards or away from the optic disc. During the ensuing 2 week period, there is a progressive growth and elaboration of dendrites. By E50, some ganglion cells resembling the adult alpha, beta, and gamma classes can be identified based on comparisons of the appearance and dimensions of their dendritic trees and somata with neighboring filled cells. However, ganglion cell dendrites and axons at this age express several transient morphological features. The axons of ganglion cells give rise to delicate processes originating from the intraretinal portion of the axon, including side branches, present in about half of the cells, and occasionally bifurcations that give rise to axon collaterals. These transient axonal features are present throughout development, including the neonatal period; no axon collaterals were observed after postnatal day 15, while axonal side branches persisted even at P31 but were gone by adulthood. Ganglion cell dendrites exhibit excessive branches and exuberant somatic and dendritic spines. Quantitative analysis of these processes shows that after E45 dendritic trees increase dramatically in complexity, reaching the peak number of spines and branch points by the first week of postnatal life. The number of dendritic processes then falls abruptly to reach near-adult levels by the end of the first postnatal month. Even though dendritic morphology closely resembles that seen in the adult at this age, ganglion cell bodies and dendrites must continue to grow to reach their adult size.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pars plana vitrectomy for refractory diabetic macular edema.

OBJECTIVE: The aim of this study is to describe the results of pars plana vitrectomy (PPV) for refractory diabetic macular edema (DME). METHODS: Review of the relevant peer-reviewed scientific literature identified using Medline. MAIN OUTCOME MEASURES: The anatomical and functional outcome of surgery. RESULTS: Vitrectomy with or without internal limiting membrane (ILM) peeling can be beneficial for the treatment of DME that is resistant to laser photocoagulation or sub-Tenon's steroid injection. Visual improvement has been reported in approximately 40-90% of patients, with approximately 85-100% experiencing either improvement or stabilization of vision. Retinal edema decreases or resolves in approximately 70-100% of patients. Complications range in severity with approximately 5-20% of patients developing peripheral retinal breaks, approximately 1-2% developing retinal detachment, approximately 2% developing macular hole, and approximately 10-60% developing cataract. Severe complications such as rubeosis iridis and the fibrinoid syndrome have also been reported. CONCLUSION: Pars plana vitrectomy can be an effective treatment for diabetic macular edema refractory to laser therapy and/or sub-Tenon's capsule steroid injection.

Diabetic Retinopathy↗

Growth and development of the mouse retinal pigment epithelium. I. Cell and tissue morphometrics and topography of mitotic activity.

A computer-assisted morphometric and kinetic analysis of retinal pigment epithelium (PE) development was carried out in C57BL/6J and hybrid mice from Embryonic Day 13 (E13) to Postnatal Day 250 (P250). Total cell number rose from 14,000 at E15 at the rate of about 4000 cells/day to P1 and then at about 1500 cells/day to reach a stable level of 54,000 cells at P15. Compared to the 4-fold rise in cell number, PE area increased about 10-fold, in part through cell hypertrophy which continued beyond P15. Cell concentration increased with distance from the optic nerve head during development, but the gradient disappeared by P20 except for a consistent population of small cells around the optic nerve head and a late-appearing population of very large cells at the ora serrata. Binucleate cells constitute 2.1% of the PE cell population at P1 and 26% at P30, almost all of them located in the posterior 75% of the PE where they comprise 70% of the cell population at some radial positions. Mitotic cells, detected by fluorescent monoclonal antibody R3, are distributed across the entire PE at E13. As the eye grows the mitotic zone occupies a progressively smaller and more distal proportion of the increasing radius; by P5 only the region near the ora serrata is highly active, with some additional mitotic cells trailing into a broad central zone. From P7 to P15 nuclear divisions persist only centrally to generate the youngest uninucleate and binucleate cells. The mouse PE thus shows a pattern of edge-biased interstitial growth (in contrast to amphibians with strict edge growth).

Animals↗

Regulation of glucose transporters during development of the retinal pigment epithelium.

The retinal pigment epithelium (RPE) separates the outer retina from its blood supply. To satisfy the retina's large requirement for glucose, the RPE expresses high levels of glucose transporters. In most rat cells, the transporter GLUT3 provides a basal level of transport, but the expression of GLUT1 can be regulated. The opposite is true in chicken (P. Wagstaff, H.Y. Kang, D. Mylott, P.J. Robbins, M.K. White, Characterization of the avian GLUT1 glucose transporter: differential regulation of GLUT1 and GLUT3 in chicken embryo fibroblasts, Mol. Biol. Cell 6 (1995) 1575-1589). We examined chick RPE to determine which isoform is regulated during development, and if the neural retina regulates GLUT expression. By RT-PCR, RPE expressed GLUT1 and GLUT3, but not GLUT2. Only the level of GLUT1 increased between E5 and E18. A corresponding increase in GLUT1 protein was observed by immunoblotting. Most of the increase occurred between E14 and E18, which corresponds to the late stage of tight junction development. A culture model of development was used to examine the intermediate phase, which extends from E7 to E14. While medium conditioned by the neural retina decreased paracellular diffusion across the tight junctions, it increased diffusion through the glucose transporters. Unlike mammals, chick upregulates different isoforms in quiescent RPE and proliferating fibroblasts. Further, the upregulation of glucose transport is coordinated with the development of tight junctions in the blood-retinal barrier.

Animals↗

[Risk of retinal detachment in pseudophakia and axial myopia].

The incidence of retinal detachment on axial myopic pseudophakic eyes after Nd:Yag laser capsulotomy or intraoperative complications varies in the literature. In this study we analysed the incidence of retinal detachment in 136 pseudophakic myopic eyes (axial length > or = 26.0 mm) with and without capsulotomy and after intraopertive complications. These results were compared with those published in the literature and those obtained in a control group of 136 pseudophakic eyes with an axial length of less than 26.0 mm. Both groups were followed up for 2 years following operations in 1989 and 1990. The incidence of retinal detachment in eyes with axial myopia > or = 26.0 mm was 3.6% (5/136), without capsulotomy 3.3% (3/90) and with capsulotomy 2.5% (1/40). Intraoperative defects of the posterior capsule occurred in 6 cases, and in 1 case retinal detachment (1/6) developed. No retinal detachment occurred in the control group. The risk of retinal detachment does not seem to be significantly higher after uncomplicated extracapsular cataract extraction in eyes with axial myopia than in myopic eyes in which cataract extraction has not been performed. The combination of capsulotomy and axial myopia does not seem to increase the risk of retinal detachment. However, intraoperative complications do increase the risk of retinal detachment. Retinal detachment is three times as likely to develop in pseudophakic myopic eyes as in eyes with normal axial length.

Adult↗