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Delayed filling of retinal and ciliary circulation after central retinal artery occlusion.

The filling times of the retinal and choroidal circulation were evaluated in 17 patients with central retinal artery occlusion by means of fluorescein angiography. A correlation between the filling times of the two circulations was found. However, two filling patterns were seen: first, both fillings delayed; second, both fillings normal. It is probable that in the former case an obstructive disease of the carotid arteries exists, while in the latter case an important pathology of the carotid arteries is lacking, favouring a rapid restoration of the retinal circulation. This hypothesis seems to be confirmed by the results of the Doppler velocimetry of the carotid arteries.

Aged↗

Dispersion of retinal pigment epithelial cells from experimental retinal holes.

The effects of cryotherapy, transcleral massage, or directed irrigation on exposed retinal pigment epithelial (RPE) cells at the base of an experimental retinal hole were studied in living rabbit eyes. Cryotherapy or massage with or without vitrectomy failed to release RPE cells or result in preretinal membrane formation. Directed irrigation dispersed viable RPE cells into the vitreous and produced cellular precipitates with membranes on the inferior retina, although the membranes tended to regress within 6 weeks after surgery. These results suggest that healthy RPE cells at the base of retinal tears are not easily released into the vitreous and may not contribute to the formation of preretinal membranes found in proliferative vitreoretinopathy.

Animals↗

New approaches to ophthalmic electrodiagnosis by retinal oscillatory potential, drug-induced responses from retinal pigment epithelium and cone potential.

New clinical methods are proposed to assess (1) neuronal activities of the retinal inner layers including amacrine cells by means of the oscillatory potential, (2) photopic function through the rapid decay in the off-response and (3) activities of the retinal pigment epithelium through susceptibility of the standing potential of the eye to osmotic stress and to Diamox. These new methods are able to reveal otherwise undetectable retinal disorders.

Acetazolamide↗

Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation from high to low glucose levels: a comparative study with retinal capillary endothelial cells.

A number of clinical observations concerning cases of glycemic fluctuation have prompted us to study whether or not a rapid change in blood glucose concentration can aggravate retinal microvascular pathology during the early stage of diabetic retinopathy. We conducted a comparative study of retinal capillary pericytes and endothelial cells in vitro. Both types of cells, either in single culture or in co-culture, were initially incubated in medium with high glucose (20-40 mmol/l), followed by a rapid reduction of glucose to 3.5, 1, or 0.5 mmol/1. This type of reduction of extracellular glucose resulted in depletion of intracellular glucose, occurring much faster in pericytes than in endothelial cells. The abrupt reduction in glucose caused pericyte cell shrinkage and nuclear condensation associated with DNA fragmentation, followed by loss of cell viability. All of these pericyte changes are apoptosis-like characteristics. This apoptotic process was prevented by the addition of cycloheximide, a protein synthesis inhibitor, or by platelet-derived growth factor BB, which is known competent factor for pericyte growth. In analysis of signalling pathways during the abrupt fluctuation of glucose, the occurrence of pericyte apoptosis was an intracellular calcium-dependent, protein kinase C and protein kinase A mediated, and poly (ADP-ribose) synthetase-dependent process. Interestingly, a larger degree of DNA fragmentation was observed with a higher magnitude and a longer duration of pre-existing hyperglycaemia. These results suggest that the magnitude and duration of pre-existing hyperglycaemia prime the apoptotic responsiveness of pericytes. Retinal capillary endothelial cells, after an identical glucose fluctuation treatment did not undergo an apoptotic process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Production of specific retinal S antigen antibodies in patients with retinal detachment.

One hundred patients with retinal detachment (61 primary operations and 39 reoperations) were studied for titers of autoantibodies to human retinal S antigen using the enzyme-linked immunosorbent assay technique (ELISA). There was no statistically significant difference when comparing the group of patients with primary retinal detachment with the control group. However, a statistically significant increase in anti-S titers was recorded when a comparison was made between the group of reoperated patients and the control group (chi 2, P less than 0.001) and between the group of reoperated subjects and the group of patients operated on for the first time (chi 2, P less than 0.005).

Antibody Specificity↗

Surgical posterior vitreous detachment combined with gas/air tamponade for treating macular edema associated with branch retinal vein occlusion: retinal tomography and visual outcome.

PURPOSE: To assess the effectiveness of surgical posterior vitreous detachment (PVD) together with gas/air tamponade in treating visual impairment from macular edema associated with branch retinal vein occlusion (BRVO-macular edema). METHODS: A cohort study was conducted. To treat visual disturbance caused by BRVO-macular edema in 19 consecutive patients at a University Hospital, phacoemulsification, intraocular lens implantation, and vitrectomy were performed, together with gas/air tamponade. Patients were followed up postoperatively for 3-18 months. Foveal structure was defined using optical coherence tomography (OCT). Preoperative visual acuity, central retinal thickness, and interval between BRVO onset and operation were compared between patients with postoperative visual improvement and those without improvement. RESULTS: Ten patients recovered normal or near-normal foveal configuration, while nine patients did not. Mean postoperative visual acuity in the former group of patients was significantly higher than in the latter. Mean foveal retinal thickness decreased significantly after the operation. The interval from onset of BRVO until operation was significantly shorter in patients with improved postoperative vision than in other patients, and patients operated on within 11 months had significantly increased postoperative visual acuity. CONCLUSIONS: Surgical PVD and gas/air tamponade appears effective in treating BRVO-macular edema, although relatively short duration from disease onset until operation is critical for improvement of vision. When a good postoperative foveal contour is seen, it seems to be associated with better visual outcome.

Adult↗

Visual outcome in central retinal and branch retinal artery occlusion.

PURPOSE: To study retrospectively the presenting visual acuity and the visual outcome in patients with central retinal artery occlusion (CRAO) and in patients with branch retinal artery occlusion (BRAO). METHODS: We studied the visual acuity and outcome in 23 patients (23 eyes) with CRAO and in 30 patients (30 eyes) with BRAO that met the inclusion criteria: a funduscopic appearance of retinal whitening, a delay in arterial dye filling in a fluorescein angiogram, the first examination in our hospital within 7 days of onset, and a minimum follow-up period of 90 days. RESULTS: Both presenting acuity and final acuity were far worse in patients with CRAO than in patients with BRAO. A final acuity worse than 0.1 was observed in 14 of the 23 (61%) patients with CRAO and in only 1 of the 30 (3%) patients with BRAO. Only 5 of the 23 (22%) patients with CRAO and 24 of the 30 (80%) patients with BRAO showed a final acuity of 0.5 or better. CONCLUSION: Visual acuity in patients with CRAO is poor at presentation, and the prognosis is generally poor, with a few exceptions. In contrast, the visual acuity in patients with BRAO is far better both at presentation and at the final visit.

Adolescent↗

Retinal ganglion cell survival and neurite regeneration in vitro after cell death period are dependent upon target derived trophic factor and retinal glial factor(s).

Retinal ganglion cells (RGCs) obtained from the rat retina after the cell death period were maintained in vitro by target derived retinal ganglion cell neurotrophic factor (RGNF). However, only 15% of surviving RGCs expressed neurites. On the other hand, when the culture was supplemented with retinal glia conditioned medium, nearly 80% of surviving RGCs expressed neurites which were longer than two cell diameter. Expression of neurites is not due to the presence of laminin in the glial conditioned medium as laminin coated substratum had no significant effect on the neurite growth from mature RGCs in the absence of glial factors.

Animals↗

Collagens of the retinal microvascular basement membrane and of retinal microvascular cells in vitro.

We have analysed the collagens present in vascular basement membranes isolated from bovine retinal and cerebral microvessels and bovine renal glomeruli, and from the non-vascular basement membrane of bovine lens capsule. These are compared with the collagens produced by cultured bovine retinal microvascular pericytes and lens epithelial cells, and by canine retinal microvascular endothelial cells, in vitro. Biochemical and immunocytochemical analyses indicate that all of the vascular basement membrane preparations have an identical collagenous composition, consisting of the same polypeptides present in lens capsule (primarily type IV collagen), together with other polypeptides that are identified as type I, and a small amount of type III collagen. Identification of the latter is based on two-dimensional gel electrophoresis in the presence and absence of a reducing agent. Immunocytochemical studies, however, demonstrate type I, type IV and some type V collagen in the basement membranes of the isolated microvessels. The cultured microvascular cells produce predominantly type I collagen molecules, but they also produce other collagen peptides that appear to be type IV, and, at least in some experiments, small amounts of type III collagen. The biochemical identification of collagens type I and IV is confirmed by immunocytochemistry. However, results with anti-type I collagen and procollagen antibodies in cultured pericytes vary with antibodies from different sources. The quantities of the type IV peptides produced by the cultured cells also vary in different experiments.

Amino Acids↗

Systemic immunostimulation after retinal laser treatment in retinitis pigmentosa.

Systemic immunostimulation followed an experimental treatment trial of scatter argon laser photocoagulation directed to the retina of one eye of 10 patients with heredo-degenerative retinitis pigmentosa (RP). Significantly increased RP lymphocyte CD25, CD26, and CD4/CD26 activation epitope expressions over prelaser values and controls were found with a normalization of soluble interleukin-2 receptor secretion after laser treatment. Serum interferon-gamma was low both pre- and postlaser. Interestingly, when a panel of viral antibodies was tested, only those to rubella virus were elevated in the early postlaser period. The character of RP immunostimulation after laser-induced inflammation could be consistent with an antigenic stimulus from laser-released retinal proteins which might be of autoimmune or latent infectious origin. Enhanced immune responses may be a common but unrecognized sequellae of retinal laser.

Adolescent↗

Retinal growth hormone is an anti-apoptotic factor in embryonic retinal ganglion cell differentiation.

Cells of the neural retina in the chick embryo undergo several waves of apoptosis during development, including peaks at approximately embryonic day (ED) 7 and 12. Prominent among the cells involved in these phases of cell death are the retinal ganglion cells (RGCs). We have previously shown that growth hormone (GH) is expressed in the neural retina, and particularly, in the RGCs. Here we study the ability of GH to rescue retinal cells from apoptosis, both in vitro and in vivo. When retinas from embryos at ED 6-8 are explanted on collagen gels, the application of recombinant GH, at 10(-6)m, significantly reduced the incidence of apoptotic cells in the cultures as judged by terminal deoxynucleotide transferase-mediated dUTP-biotin nick end labelling (TUNEL). GH was delivered to neural retinas in ovo, by microinjection into the eye cup at ED 2. When these embryos were examined at ED 6-8, no reduction in cell death was observed below the normal low control levels. However, when antibodies to GH were microinjected, the incidence of cell death increased significantly at ED 6, providing evidence that in vivo immunoneutralization of endogenous GH results in triggering of apoptotic signaling pathways. Evidence that RGCs are a particular target of this neuroprotective effect of GH was provided by examination of cultures enriched for RGCs by immunopanning. In serum-free culture, RGCs, identified by anti-Islet 1 immunolabelling, were found to be susceptible to the effect of GH immunoneutralization, which approximately quadrupled the incidence of apoptosis in the cultures. We propose that GH is a naturally occurring autocrine and/or paracrine neuroprotective agent in the developing retina which is involved in the regulation of retinal cell numbers during early embryogenesis.

Animals↗

Organization of the canine gene encoding the E isoform of retinal guanylate cyclase (cGC-E) and exclusion of its involvement in the inherited retinal dystrophy of the Swedish Briard and Briard-beagle dogs.

Intracellular cyclic GMP concentration is known to change in response to a wide variety of agents, including hormones, neurotransmitters or light. In vertebrate photoreceptors, different membrane-bound guanylate cyclase isoforms are responsible for cGMP synthesis and thus directly involved in termination of light signalling via the phototransduction cascade and recovery of the dark state. We have characterized a 4.7 kb long cDNA for the canine retinal guanylate cyclase isoform E (cGC-E) predicting a polypeptide of 1109 amino acids. The genomic structure and the complete sequence of the canine GC-E gene, which consists of 20 exons and spans about 14.5 kb, has also been determined. Northern blot analysis showed that GC-E was expressed in the canine retina as a 4.7 and 6.1 kb large transcript. RT-PCR analysis also detected low expression in cerebrum (occipital lobe). We performed a sequence analysis of the cGC-E gene in animals of a Swedish Briard and Briard-Beagle dog kinship in which an inherited retinal dystrophy is segregating. Several intragenic DNA polymorphisms were identified and used for segregation analysis which excluded cGC-E as a candidate gene for this type of canine retinal dystrophy.

Amino Acid Sequence↗

Development of the blood-retinal barrier in vitro: formation of tight junctions as revealed by occludin and ZO-1 correlates with the barrier function of chick retinal pigment epithelial cells.

To elucidate the molecular mechanisms of the blood-retinal barrier (BRB), we examined chick retinal tissues histochemically using antibodies against tight junction proteins such as ZO-1, 7H6 antigen, and occludin. Retinal pigment epithelial (RPE) cells in situ in chickens and late chick embryos expressed all of the tight junctional proteins examined, showing that tight junctions seal the cell borders of chick RPE cells in vivo. On the other hand, RPE cells isolated from late chick embryos and transferred in vitro did not express occludin, ZO-1 and 7H6 antigen. The effects of differentiation-inducing agents, such as retinoic acid, dexamethasone and dimethyl sulfoxide (DMSO) were tested. Only DMSO induced an increase in transepithelial electrical resistance (TER) in a time-dependent manner. Under supplementation with DMSO, immunofluorescently demonstrable occludin and ZO-1 were induced progressively at cell borders in parallel with the increase in TER that occurred with decreases in inulin and dextran permeability. Electron microscopically tight junction-like junctional apparatus were induced in RPE cells. These results indicated that tight junctions of RPE cells play an important role in the formation of the BRB.

Animals↗

Multicenter genetic study of retinitis pigmentosa in Japan: II. Prevalence of autosomal recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of genetically heterogeneous diseases with autosomal recessive (AR), autosomal dominant, and X-linked modes of inheritance. Autosomal recessive retinitis pigmentosa (ARRP) is the most common form in Japan. A genetic analysis was done to determine the prevalence of ARRP indirectly, to provide an estimation of changing trends in the overall prevalence of RP. Data on the frequency of consanguinity and marriage year of normal parents of 59 ARRP patients were obtained from a nationwide multicenter survey of typical retinitis pigmentosa conducted in 1990. The gene frequency of ARRP was 0.01145 (Dahlberg's formula). In 1990, the number of young symptomatic ARRP patients decreased, while the number of patients aged 40 years and older increased. The total number of symptomatic ARRP patients in 1990 was nearly 21% higher than in 1970. Despite a dramatic decline in consanguinity in recent decades in Japan, the number of ARRP patients has increased. This increase is attributed to greater longevity and overall population growth. Our results suggest that the total number of RP patients has not decreased, and may even have increased.

Adolescent↗

Assessment of local retinal function in patients with retinitis pigmentosa using the multi-focal ERG technique.

To assess local retinal function in patients with retinitis pigmentosa (RP), multi-focal ERGs and local thresholds (static visual fields) were obtained on eight RP patients with visual acuities of 20/25 or better. All eight patients showed multi-focal responses with normal timing within the central 5 deg. However, there were few responses with normal timing in the areas outside the central 7.5 deg, except in the case of the only patient with a 30 Hz full-field response with normal timing. Since full-field ERGs are dominated by responses from the periphery, this finding supplies a foundation for the commonly observed delays in the full-field cone ERGs of patients with RP. With respect to amplitude, only two patients showed multi-focal responses with near normal amplitudes anywhere in the field. The loss of amplitude at any point was not a good predictor of visual sensitivity in the Humphrey visual field. On the other hand, all areas with normal timing had near normal sensitivity. Timing changes appear to be an early indication of local retinal damage to the cone system. Nearly all areas with sensitivity losses greater than 0.5 log unit, and some areas with near normal sensitivity, showed significantly delayed multi-focal ERGs. Finally areas with extreme sensitivity loss show multi-focal responses with a wide range of amplitudes and implicit times across patients, suggesting different mechanisms of disease action in different patients.

Adult↗

Retinal detachment with atopic dermatitis similar to traumatic retinal detachment.

PURPOSE: The cause of retinal detachment (RD) with atopic dermatitis remains uncertain. The purpose of this study is to show that the probable cause of RD with atopic dermatitis is ocular contusion. METHODS: The authors retrospectively compared the fundus findings of 24 eyes (16 patients) that had RD and atopic dermatitis with 36 eyes (36 patients) that had traumatic RD. RESULTS: The authors found similar characteristics. Retinal breaks at vitreous base borders characterized by ocular contusion occurred in 79.2% of eyes with RD and atopic dermatitis and in 75.0% of eyes with traumatic RD. Irregular retinal traumatic breaks in the equatorial zone occurred in 20.8% of eyes with RD and atopic dermatitis and in 47.2% of eyes with traumatic RD. Objective signs of ocular contusion outside the retina appeared in 54.2% of eyes with RD and atopic dermatitis. CONCLUSIONS: The authors' data support the conclusion that self-inflected ocular contusion by tapping the eyes can cause RD with atopic dermatitis.

Adolescent↗

[Proliferative diabetic retinopathy: vitreo-retinal complications are often related to insufficient retinal photocoagulation].

INTRODUCTION: Panretinal photocoagulation proved to be effective in preventing complications related to vasoproliferative diabetic retinopathy. Surgery is most often a last resort in cases of recurrent or persistent vitreous hemorrhage or retinal detachment. The aim of our study is to point out that eyes requiring surgery for complications related to vasoproliferative diabetic retinopathy are often insufficiently photocoagulated. PATIENTS AND METHODS: Retrospective analysis of operating protocols and surgical results for a series of 39 eyes of 36 patients with complications of vasoproliferative diabetic retinopathy. RESULTS: The mean age at the intervention was 57 years. Eighty-five percent of the eyes had a vitreous hemorrhage, 17% a retinal detachment. Eighty-five percent of the eyes had undergone a partial retinal photocoagulation before surgery. All eyes underwent a vitrectomy with segmentation of fibrovascular membranes. In 85% of the eyes studied, endolaser photocoagulation was necessary, sometimes even in the mid-periphery. After 39+/-26 months of postoperative follow-up, 97% of eyes showed improvement of the anatomical state of the retina and improvement or stabilization of visual acuity. CONCLUSION: Our results confirm the benefit of vitreoretinal surgery in complications related to vasoproliferative diabetic retinopathy. Moreover, it should be emphasized that complications requiring surgery often result from incomplete preoperative photocoagulation. To be effective, photocoagulation has to destroy more than 35% and up to 50% of photoreceptors. An intraoperative laser extension can reduce the risk of regrowth of fibrovascular membranes.

Diabetic Retinopathy↗

Retinal ganglion cell axon diameter spectrum of the cat: mean axon diameter varies according to retinal position.

Axon diameters of retinal ganglion cells were measured from electron micrographs of the nerve fiber layer of the cat. Three adult retinae were examined which had mean axonal diameters of 1.18 +/- 0.86 (n = 5553), 1.12 +/- 0.79 (n = 7265), and 1.47 +/- 1.11 microns (n = 10,867). Cumulative histograms from several locations adjacent to the optic disc were unimodal (modal peaks: 0.6-0.8 microns). This unimodal distribution, however, did not reflect the regional differences in axonal diameters found throughout the retina. In many locations, especially those related to axons of the temporal retina, axon diameter distributions were clearly bimodal or even trimodal (modal peaks: 0.6-0.8, 1.4-2.1, and 3.3 microns). Measurements from one retina indicated that the mean diameters of axons arising from the area centralis and visual streak (0.94 +/- 0.63 and 0.98 +/- 0.68, respectively) were not significantly different from each other; however, when compared to other areas around the optic disc, the percentage of fibers with diameters between 1.5-2.0 microns was highest in the sample adjacent to the area centralis. Axons temporal to the optic disc were found to be on average larger than those nasal to the optic disc; similarly superior axons were larger than inferior axons. Axonal distributions at the retinal periphery were found to be significantly different from those at the optic disc (P < or = 0.05) and contained a higher percentage of medium-sized axons and fewer small axons. In each of the three retinae the proportions small, medium, and large axons were respectively gamma: 46; 47; 48, beta: 50; 49; 48, and alpha: 4; 4; 4; regional differences in the proportions of each axonal class are compared to previously published ganglion cell density maps. Differences between axonal bundles within each sample location were not significantly different; however, in one retina axons in the scleral half of the fiber layer were significantly larger (P < or = 0.01) than axons in the vitreal half of the nerve fiber layer adjacent to the optic disc. When compared to the axonal diameter distributions found within the optic nerve (Cottee et al., 1991) and optic tract (Reese et al., 1991), our data indicates that the diameter of retinal axons may increase by up to 30% along the length of the visual pathway.

Animals↗