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Electrophysiological properties of rat retinal Müller (glial) cells in postnatally developing and in pathologically altered retinae.

Retinal glial Müller cells are characterized by dominant K(+) conductances. The cells may undergo changes of their membrane currents during ontogeny and gliosis as described in rabbit and man. Although the rat retina is often used in physiological experiments, the electrophysiology of rat Müller cells is less well studied. The aim of the present study was to characterize their membrane currents in postnatal development and in two models of retinal degeneration. Freshly isolated cells were subjected to whole-cell patch clamp recordings. During the first 4 weeks after birth of rats, their Müller cells displayed an increase in all membrane currents, particularly in the inward currents elicited at hyperpolarizing potentials. The decrease of the membrane resistance from more than 760 MOmega to less than 50 MOmega was accompanied by a shift of the zero current potential from about -20 mV to -80 mV, similar as earlier observed in developing rabbit Müller cells. These developmental changes were found in pigmented Brown Norway rats as well as in rats with inherited retinal dystrophy (RCS rats). Moreover, an infection of Lewis rats with the Borna disease virus caused substantial neuroretinal degeneration but did not result in a strong reduction of inward currents and of the zero current potential of the Müller cells. Thus, rat Müller cells fail to change their basic membrane properties in two different models of retinal pathology. This is in contrast to human and rabbit Müller cells, which have been shown to undergo dramatic changes of their membrane physiology in response to retinal diseases and injuries.

Animals↗

Tissue oxygen levels control astrocyte movement and differentiation in developing retina.

Astrocytes play a key role in the development of retinal vessels by detecting hypoxia in developing retina and secreting the hypoxia-induced angiogenic factor VEGF to induce vessel formation. The astrocytes which play this role are themselves spreading over the retina, just ahead of the growing vessels. To understand the mechanisms which keep astrocytes in this strategic 'just ahead' position we have studied the effects of hyperoxia and hypoxia on astrocyte differentiation and movement in situ in neonatal rat retina and in primary culture. Hyperoxia in situ inhibited the stellation of astrocytes, so that they persisted in a relatively unbranched form, which accumulated at the edge of their spreading population; hyperoxia permitted but did not accelerate migration. Conversely, hypoxia induced unstellated astrocytes to stellate within 6 h. If the hypoxia was abnormally severe, it caused the astrocytes to hyperstellate and slowed their spread. Astrocytes in primary culture did not change morphology or motility when challenged by hypoxia. When treated with medium conditioned by retina however, astrocytes became mobile and, if the medium was conditioned by hypoxic retina, became stellate. These results suggest that the oxygen released by retinal vessels maintains the mobility of astrocytes, via a diffusible factor released by other retinal cells. Conversely, naturally generated hypoxia of developing retina plays a triple role, inducing astrocytes to stellate, to end their migration and to produce VEGF, thereby inducing vessel formation. The induction of stellation is mediated by a diffusible factor released by other retinal cells. Thus hypoxia of the retina generated by neural maturation induces key events in both the differentiation of astrocytes and the formation of blood vessels.

Aging↗

The relation of retinal sensitivity and rhodopsin in developing rat retina.

The authors have studied the relations of rhodopsin and retinal sensitivity in developing albino rats, (1) in the dark-adapted state and (2) after exposure to light that bleaches greater than 90% of rhodopsin. Developmental increases in dark-adapted b-wave sensitivity and rhodopsin content were related directly as has been reported previously for rhodopsin and PIII sensitivity of other developing retinas. During dark-adaptation, infant rat log a-wave and log b-wave sensitivities and adults' log b-wave sensitivity were related linearly to the proportion of rhodopsin present. The authors suspect that the sensitivity-rhodopsin relations of infant rat retina are determined mainly by photoreceptor processes. Thus, the infant rat provides a model for investigation of mechanisms underlying both (1) the direct relation of sensitivity and rhodopsin and (2) the log sensitivity-rhodopsin relation.

Animals↗

Selective photoreceptor damage in albino rats using continuous blue light. A protocol useful for retinal degeneration and transplantation research.

PURPOSE: To develop a retinal degeneration model with selective photoreceptor loss and RPE sparing, to be used as recipient for evaluating retinal transplants. METHODS: Albino rats were exposed to blue light, continuously, for 1-7 days (24-168 h) in a specially designed cage. Eyes were histologically analyzed at periods between 2 h and 8 months after the light exposure. Electroretinograms (ERGs) were recorded from some rats at 12-216 days after exposure. Using behavioral methods, visual thresholds of some rats were determined before exposure and re-measured between 18 and 52 days following exposure. RESULTS: Apoptotic nuclei appeared exclusively in the photoreceptor layer after 1-5 days exposure to blue light. Light microscopy revealed that 2-4 days of light exposure reduced the outer nuclear layer (normally eight to ten rows) to 1 row of cells in the central retina and to two to three rows in the periphery, both in the superior and the inferior retina. Average ERG a- and b-wave amplitudes of light-damaged rats were both reduced by about 98%. Visual performance in the behavioral test was substantially impaired. CONCLUSIONS: Continuous exposure of albino rats to moderate blue light for 2-5 days selectively eliminates most of the photoreceptors while leaving the RPE initially intact.

Animals↗

Unilateral varicella zoster virus ophthalmicus and contralateral acute retinal necrosis.

We report two patients who developed varicella zoster virus (VZV) ophthalmicus complicated by ipsilateral keratouveitis, and within 4 weeks developed acute retinal necrosis (ARN) in the contralateral eye. The ipsilateral retina was spared in each case. One patient had systemic lupus erythematosus (SLE) and the other Hodgkin's disease. Both patients were in remission at the time of presentation.

Adult↗

Seasonal variations in the onset of retinal vein occlusion.

Seasonal variation in the development of retinal vein occlusion in 1003 consecutive patients with various types of retinal vein occlusion was studied prospectively from 1973 to 1990. No seasonal variation in the onset of any type or combination of types of retinal vein occlusion was found. This refutes previous reports of such seasonal variation, which were based on small retrospective series.

Adult↗

The diagnosis of cytomegalovirus retinitis.

Immunosuppressed patients are at risk for developing cytomegalovirus retinitis. This disorder is the most common cause of vision loss in patients with the acquired immunodeficiency syndrome (AIDS). Cytomegalovirus retinitis is probably the result of hematogenous spread of the virus to the retina after systemic reactivation of a latent cytomegalovirus infection. Although the ophthalmic infection may initially be asymptomatic, the retinal necrosis it produces may result in both loss of visual field and decreased visual acuity. Routine screening of these patients is required for early diagnosis. The retinitis is detected with ophthalmoscopy as either a perivascular yellow-white retinal lesion frequently associated with retinal hemorrhage or as a focal white granular infiltrate, often without hemorrhage. Both lesions enlarge in a progressively expanding "brushfire" pattern. The diagnosis of cytomegalovirus retinitis, as well as the evaluation of its response to therapy, is determined primarily by clinical criteria. Serial retinal photography is an objective method to assess the changing appearance of these lesions. Ganciclovir and foscarnet are investigational antiviral drugs that appear to be effective in treating cytomegalovirus retinitis. However, maintenance therapy with these medications is required after initial treatment because the disease often relapses. The combined expertise of the internist and the ophthalmologist is needed to diagnose and treat these patients.

Acquired Immunodeficiency Syndrome↗

Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress.

The retina experiences mitochondrial dysfunction in diabetes, superoxide levels are elevated, and mitochondrial superoxide dismutase (MnSOD) activity is decreased. Inhibition of superoxide accumulation in diabetes prevents mitochondrial dysfunction, apoptosis of retinal capillary cells, and the development of retinal histopathology. The purpose of this study is to examine the effect of overexpression of MnSOD on oxidative stress, DNA damage, and nitrative stress in the retina of diabetic mice. After 7 weeks of diabetes in MnSOD overexpressing (hemizygous) mice (MnSOD-Tg) and in their age-matched nontransgenic mice, parameters of oxidative stress and nitrative stress were measured in the retina. Overexpression of MnSOD prevented diabetes-induced decreases in retinal GSH levels and the total antioxidant capacity. In the same retina, MnSOD overexpression also inhibited diabetes-induced increases in the levels of 8-OHdG and nitrotyrosine. This suggests that MnSOD could be implicated in the pathogenesis of retinopathy by protecting the retina from increased oxidative damage experienced in diabetic conditions. Thus, understanding how changes in mitochondrial function result in the development of diabetic retinopathy could help identify SOD mimics to inhibit its development.

Animals↗

Retinal ganglion cell dendritic development and its control. Filling the gaps.

The way in which central neurons acquire their complex and precise dendrite arbors is of considerable developmental interest. Using retinal ganglion cells (RGCs) as a model, the mechanisms that pattern dendritic development are beginning to emerge. As in other systems, final dendrite phenotype is achieved by a mixture of intrinsic and extrinsic determinants. The extrinsic determinants of RGC dendrite shape reflect the anatomical constraints of producing a paracrystalline mosaic of arbors that laminates the inner plexiform layer of the retina. In this article, the key features of RGC dendrite development are reviewed. The emerging molecular mechanisms behind dendritic laminar segregation and "dendritic competition" are described. The role of afferent extrinsic influences are contrasted with those of retrograde, activity-dependent target influences that may regulate the final maturational phase of dendrite remodeling.

Animals↗

Association of candidemia and retinopathy of prematurity in very low birthweight infants.

OBJECTIVE: To determine if the presence of candidemia in infants is associated with an increased incidence of threshold retinopathy of prematurity (ROP). DESIGN: Retrospective, case-controlled study. PARTICIPANTS AND CONTROLS: Forty-six infants admitted to the Texas Children's Hospital Neonatal Intensive Care Unit between 1989 and 1999 with a birth weight 1500 g or less, estimated gestational age (EGA) 28 weeks or less, and in whom candidemia developed were matched to a control group of 46 infants based on corresponding birth weight, EGA, and year of birth. METHODS: Records of each infant were reviewed to determine the presence and severity of ROP. MAIN OUTCOME MEASURES: Development of threshold ROP, including retinal detachment. RESULTS: Forty-three infants (93.5%) with candidemia and 39 (84.8%) without candidemia had ROP. Twenty-four infants (52.2%) with candidemia reached threshold and required surgical intervention, compared with 11 infants (23.9%) without candidemia (adjusted odds ratio [OR], 7.4; 95% confidence interval [CI], 1.7-32.1; P = 0.008). Retinal detachment developed in 10 of 24 candidemic infants (41.7%) who reached threshold ROP, compared with 2 of 11 infants (18.2%) without candidemia (OR, 4.4; 95% CI, 0.73-26.9; P = 0.1). CONCLUSIONS: Candidemia is associated with increased risk of threshold ROP. Infants with Candida sepsis should be monitored closely for the development of ROP and progression after treatment.

Candidiasis↗

Retinal topography in reef teleosts. I. Some species with well-developed areae but poorly-developed streaks.

The retinal ganglion cell layer of five species of teleosts has been studied from Nissl-stained whole-mounts and the distribution of neuronal elements determined quantitatively. Isodensity contour maps of neurons in the ganglion cell layer revealed areas of high density (areae centrales) predominantly in the temporal retina, but other areae were also found in the nasal and dorso-nasal retina. Neuronal densities within the ganglion cell layer at the areae centrales ranged from 0.4 x 10(4) to 4.7 x 10(4) cells/mm2. Species that were found to lack a horizontal streak of high ganglion cell density appear to be those whose behaviour suggests they possess an interrupted view of the sand-water horizon and are 'enclosed' species. Concentric density contours around an area centralis seem to be associated with enclosed environments. The relationship between retinal topography and niche is also discussed.

Animals↗

Spatial arrangement of radial glia and ingrowing retinal axons in the chick optic tectum during development.

Neuroanatomical tracing of retinal axons and axonal terminals with the fluorescent dye, DiI, was combined with immunohistochemical characterization of radial glial cells in the developing chick retinotectal system. Emphasis was placed on the mode of the tectal innervation by individual retinal axons and on the distribution and fate of the tectal radial glial cells and their spatial relation to retinal axons. It was obvious from fluorescent images obtained from anterogradely filled axons that these axons deserted the superficial stratum opticum (SO) to penetrate the stratum griseum et fibrosum superficiale (SGFS) by making right-angled turns within the SO. Frequently, axons which had invaded the SGFS were bifurcated and had a superficial branch which remained within the SO. Terminal axonal arborization occurred at various depths within the SGFS. Characterization of the tectal glial cells and their radial fibers by means of the anti-filament antibody, R5, and post-mortem staining with the fluorescent dye, DiI, revealed the following. (a) At least from day E8 to P1, tectal glial fibers traversed all tectal layers from the periventricular location of their somata to the superficial interface between SO and pia mater. In this interface they enlarged and formed characteristic endfeet. (b) Glial endfeet covered the whole tectal surface. They showed at early ages anterior-posterior differences having a higher density in the posterior tectum. These differences disappeared at embryonic day E13. (c) After innervation, glial endfeet of the anterior tectal third were arranged in rows parallel to the retinal fibers within the SO. This arrangement was not observed in eyeless embryos. (d) Radial glial fibers could be stained with R5 from day E8 to late embryonic stages throughout their entire length. (e) At the first posthatching days, only the segments of the radial glial fibers restricted to the thickness of the SO were R5-positive, although the fibers still traversed throughout the depth of the tectum. The results are discussed in context to the genesis of the retinotectal projection.

Animals↗

Comparison of retinal lesions in alloxan-diabetic rats and galactose-fed rats.

Galactose-fed rats develop a retinal microvascular disease, but retinopathy has not been found to develop reproducibly in diabetic rats. We sought to determine which retinal lesions can be reproducibly produced by long-term diabetes in rats, the extent to which the capillary lesions in diabetic rats and galactosemic rats are similar, and whether the retinopathy induced by 50% galactose can be reproduced satisfactorily by a lower concentration of galactose. Alloxan-diabetic rats and rats fed either a 50% galactose diet or a 30% galactose diet were killed after comparable durations of study (18 to 22 months). Rats fed 50% galactose showed greater than normal frequency of retinal pericyte ghosts and acellular capillaries, and thickening of capillary basement membranes by 18 months of galactosemia. Rats eating 30% galactose developed similar retinal lesions, and tended to be healthier than rats fed 50% galactose. Diabetes of 1 1/4 years or more likewise resulted in retinal pericyte ghosts, acellular capillaries and thickened capillary basement membrane. IRMAs and other vascular abnormalities were not reproducibly demonstrated at this duration of study, and saccular microaneurysms were not seen in any groups. In a number of diabetic rats, the severity of diabetes diminished spontaneously (after 1 to 1 1/2 years of insulin deficiency), thus making it essential that glycemia be systematically monitored. Both diabetic rats and experimentally galactosemic rats develop microvascular lesions that are consistent with at least the early stages of diabetic retinopathy, and these models should be useful to screen potential therapies for their ability to inhibit the development of retinopathy.

Alloxan↗

Development and role of retinal glia in regeneration of ganglion cells following retinal injury.

AIMS/BACKGROUND: Recent observations have shown that the glial scar resulting from a surgical lesion of the immature retina differs from elsewhere in the central nervous system, in that it permits the through growth and reconnection of regenerating axons. This study in the opossum examines in detail the development and reaction to injury of retinal glia at different developmental stages, and specifically examines the distribution of the gliosis related inhibitory molecule, chondroitin sulphate proteoglycan (CSPG), making comparisons with a control site of gliosis in the cerebral cortex. METHODS: A linear slit was cut into the retina or cortex with a fine tungsten probe. After a variable time delay, immunocytochemistry of the resulting gliosis was employed to detect astrocytes with glial fibrillary acidic protein (GFAP), Müller cells with vimentin, and CSPG with CS-56 antibodies. GFAP was also used at different ages to examine the normal development of astrocytes in the retina of this species. RESULTS: Astrocytes entered the retina 12 days after birth (P12), closely associated with blood vessels in the nerve fibre layer. In experiments at all ages studied, cellular continuity was re-established across the lesioned retina, which did not result in a significant astrocyte proliferation or CSPG expression. In contrast, cortical injury led to the development of a cystic cavity surrounded by astrocytes and CSPG. Müller cells expressed GFAP but not CSPG in the lesioned retina. CONCLUSION: Successful regrowth of ganglion cells through a retinal lesion may be partly the result of the scarcity of astrocytes in the retina, which results in minimal gliosis, or of their apparent inability to express inhibitory molecules.

Animals↗

Effects of X-rays on the induction of somatic mutations and growth in the retinal pigmented epithelium during development of the mouse eye.

The coat and eye colour mutant beige (bg) leads to the production of distinctive retinal melanocytes with abnormally large pigment granules. Heterozygotes for bg were given 2 Gy acute X-irradiation at various times between day 11.5 of fetal life and 3 days after birth, at which age whole mounts were prepared of the retinal pigmented epithelium (RPE). These were scanned for the presence of mutant retinal melanocytes with large granules, either as single cells or as clones. The earlier the fetal irradiation, the greater was the effect on RPE area at 3 days post-partum (p.p.), which fell to about half normal with the 11.5-day fetal exposures. However, the ultimate size of the retinal melanocytes seemed little affected by the irradiation, although their normal size increased approximately 3-fold between 12.5 days post-coitum (p.c.) and 3 days p.p. Mean numbers of mutant melanocytes per eye were markedly higher than in +/bg controls at all irradiation ages other than 3 days p.p.; when allowance was made for final sizes of irradiated RPE's mutation frequencies fell steadily from 30.0 x 10(-5) at 11.5 days p.c. to 1.0 x 10(-5) at 3 days p.p., with 0.8 x 10(-5) in +/bg and 0.1 x 10(-5) in +/+ controls. The doubling dose of 0.18 Gy at 16.5 days p.c. was similar to that found at 17.5 days p.c. in a previous somatic mutation experiment in which follicular melanocytes were scanned for mutations at different (d and ln) loci.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Prophylactic laser photocoagulation in hereditary snowflake vitreoretinal degeneration. A family report.

Examination of 37 members of a family revealed that 17 had snowflake vitreoretinal degeneration. All those affected showed some evidence of vitreous degeneration and 13 had retinal changes with differing degrees of severity. Vitreal changes may thus present as an early stage when hardly any retinal pathology is apparent. Peripheral retinal neovascularization was seen in four patients. Rhegmatogenous retinal detachment developed in two eyes and retinal breaks in six additional eyes. Because of the poor surgical prognosis in such cases, prophylactic treatment with argon laser photocoagulation is recommended for any type of retinal break.

Adolescent↗

Central retinal artery occlusion after radial optic neurotomy in a patient with central retinal vein occlusion.

PURPOSE: To describe a patient with a central retinal vein occlusion (CRVO) who developed central retinal artery occlusion after radial optic neurotomy. DESIGN: Interventional case report. METHODS: A 70-year-old woman with CRVO underwent a radial optic neurotomy on her right eye. Her preoperative visual acuity in the affected eye was 20/400. RESULTS: Radial optic neurotomy was performed after phacoemulsification and aspiration for a cataract with intraocular lens implantation. At the insertion of a CRVO knife, pulsating bleeding occurred from the cup of the optic disk; the bleeding was stopped within 2 minutes by elevating the intraocular pressure to 80 mm Hg. On the following day, the patient noticed that she had lost light perception. Fluorescein angiography showed a marked delay of arterial filling, indicating a central retinal artery occlusion. Retinal circulation returned to normal 2 months later; however, her vision was still no light perception. CONCLUSIONS: Ophthalmologists should be aware that severe complications such as central retinal artery occlusion can be associated with radial optic neurotomy, which is an unproven surgical procedure with a questionable pathophysiologic mechanism.

Aged↗

Primary intraocular lens implantation in infants: complications and visual results.

PURPOSE: To evaluate the complications and visual results in a consecutive series of patients having cataract extraction with intraocular lens (IOL) implantation in the first year of life. SETTING: St. Erik's Eye Hospital, Stockholm, Sweden. METHODS: This retrospective study comprised 28 children (31 eyes) who had cataract surgery with primary IOL implantation. RESULTS: The median age at surgery was 2.5 months (range 8 days to 10 months). The median follow-up was 36 months. Two newborns with persistent fetal vasculature (PFV) who had surgery at 8 days and 17 days, respectively, developed intraoperative vitreous hemorrhage; a retinal detachment developed in 1 of the eyes. Intraocular lens luxation occurred in 2 infants with PFV. Seventy percent of eyes developed opacification of the visual axis that required additional surgery. Chronic glaucoma developed in 2 eyes and transitory glaucoma in 1 eye. Two of the glaucoma cases occurred in eyes with PFV. In 7 eyes of 4 infants with bilateral cataract, the median visual acuity was 20/63 (range 20/25 to 20/100). In 12 infants with unilateral cataract without PFV, 7 achieved a visual acuity between 20/32 and 20/200 (median 20/63), 4 achieved counting fingers (CF), and 1 achieved light perception. In 12 eyes with PFV, 2 achieved a visual acuity of 20/200 and the rest achieved CF or worse. CONCLUSIONS: After-cataract with membrane formation was the main complication in infants with primary IOL implantation. The glaucoma incidence was low at the last follow-up.

Acrylic Resins↗