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Inhibition of alpha(1-6)-linked fucose decreases inner retinal cells and increases photoreceptors in chicken retinal reaggregates.

We investigated the developmental role of alpha(1-6)-linked fucose, applying Aleuria aurantia lectin to a specific retinal regeneration system. Thereby, dissociated retinal cells of chicken embryos reaggregate, proliferate, and differentiate in vitro into histotypical spheres, so-called retinospheroids. Under the influence of A. aurantia lectin, processes of proliferation, differentiation and histogenesis of retinospheroids were disturbed. Extending these in vitro studies, we here show that A. aurantia lectin treatment decreases cells of the inner half retina and their processes into inner plexiform layer areas, as revealed by quantitative enzyme histochemistry for butyryl- and acetylcholinesterase, and immunohistochemistry using antibodies to acetylcholinesterase, Pax-6, calbindin-D, and F11. Concomitantly, the number of rod and red/green photoreceptors dramatically increases, using the antibodies rho4D2 and CERN901 (both specific for rods) and CERN906 (specific for red/green cones). These findings show that glycoproteins exhibiting fucose in alpha(1-6)-linkage are involved in processes determining retinal cell fate, strongly shifting the relative ratio of cells of the inner towards cells of the outer retina.

Acetylcholinesterase↗

Retinal cyclic GMP and AMP in rod-cone dysplasia: comparison of assays in fixed and unfixed retinal tissues.

The effects of 3 fixatives (formalin, Bouin's solution and glutaraldehyde-paraformaldehyde) on retinal cyclic AMP and GMP content were determined in canine eyes with a known abnormality of cyclic GMP metabolism. Cyclic nucleotides were measured by radioimmunoassay on perchloric acid (PCA)-precipitated retinal samples from fixed (left) and unfixed (right) eyes from nine 6-week-old rod-cone-dysplasia-affected Irish setter dogs. Cyclic AMP values were significantly lower for fixed retinas than for unfixed controls. Retinal cyclic GMP values were also lower from glutaraldehyde-paraformaldehyde-fixed samples, but were not different from control values for formalin- or Bouin's-fixed eyes, when the retina was PCA-precipitated promptly after fixation.

Animals↗

Clinical survey of the forms, number and localization of retinal tears in cases of relapses and recurrences in retinal detachment.

This study deals with the clinical observations of the different forms and shapes of retinal tears, their number and localizations in cases of relapses and recurrences in retinal detachement surgery. Two groups of patients were considered, the first belongs to our own centre and the second to referred patient operated in other hospitals. 45.1% of both groups account for relapses. We find 7.35% of undetected retinal breaks. The greater number of tears are mainly distributed in the temporal quandrants. The most common shapes of breaks are the punched-out hole, fingernail-tip-like tears, small and medium horseshoe tears, oval and 'pebbled'-like (cluster of microholes) holes. Approximately 25% of the breaks were seen in areas where thermotherapy had not been applied and 15% of them were found beside most probably overtreated areas.

Female↗

Retinal leakage in retinal vein occlusion: reduction after hyperbaric oxygen.

A 54-year-old woman with a history of bilateral central retinal vein occlusion, probably due to an inflammatory process, developed a hemispheric retinal vein occlusion with cystoid macular edema in her only seeing eye. Five months later, in the absence of improvement in vision and macular edema, she received on two occasions a 2-weekly course of twice daily 100% hyperbaric oxygen. After each course retinal leakage, as assessed by vitreous fluorophotometry, decreased from abnormal to the normal range while visual acuity improved by two lines. The possible implications are discussed.

Female↗

The relationship between retinal ganglion cell function and retinal nerve fiber thickness in early glaucoma.

PURPOSE: To compare relative reduction of retinal ganglion cell (RGC) function and retinal nerve fiber layer (RNFL) thickness in early glaucoma by means of steady-state pattern electroretinogram (PERG) and optical coherence tomography (OCT), respectively. METHODS: Eighty-four persons with suspected glaucoma due to disc abnormalities (GS: mean age 56.6 +/- 13.8 years, standard automated perimetry [SAP] mean deviation [MD] -0.58 +/- 1.34 dB) and 34 patients with early manifest glaucoma (EMG, mean age 65.9 +/- 10.7 years, SAP MD -2.7 +/- 4.5 dB) were tested with PERG and OCT. Both GS and EMG patients had small refractive errors, corrected visual acuity > or =20/25, and no systemic or retinal disease other than glaucoma. RESULTS: MDs from age-predicted normal values were larger for PERG amplitude (GS: -1.113 dB; EMG: -2.352 dB) compared with the PERG-matched RNFL thickness (GS: -0.217 dB; EMG: -0.725 dB). Deviations exceeding the lower 95% tolerance intervals of the normal population were more frequent for PERG amplitude (GS: 26%; EMG: 56%) than PERG-matched RNFL thickness (GS: 6%; EMG: 29%). CONCLUSIONS: In early glaucoma, reduction in RGC electrical activity exceeds the proportion expected from lost RGC axons, suggesting that a population of viable RGCs in the central retina is dysfunctional. By combining PERG and OCT it is, in principle, possible to obtain unique information on reduced responsiveness of viable RGCs.

Aged↗

A mouse model of gyrate atrophy of the choroid and retina. Early retinal pigment epithelium damage and progressive retinal degeneration.

Gyrate atrophy (GA) of the choroid and retina is a blinding chorioretinal degeneration caused by deficiency of ornithine delta-aminotransferase (OAT). The phenotype of GA is characterized by progressive concentric reduction of the visual fields and ornithine accumulation. To understand better the pathogenesis of GA and to develop a model to test therapeutic strategies, we produced an OAT-deficient mouse by gene targeting. Like human GA patients, adult OAT-deficient mice exhibit chronic hyperornithinemia to levels 10-15-fold above normal and massive ornithinuria. Slowly progressive retinal degeneration is reflected by a gradual decline in electroretinogram amplitudes over the first 12 mo of life. At 2 mo, the retinal pigment epithelium is histologically normal, but electron microscopy reveals sporadic degeneration of scattered pigment epithelial cells. By 6 mo there are more diffuse abnormalities of the pigment epithelium with accumulation of large phagosomes and crystalloid inclusions. Although morphologically normal at 2 mo, the photo-receptor outer segments become highly disorganized and shortened to 60% of control length by 10 mo. Additionally, there is cumulative loss of the photoreceptor cells, which reaches 33% by 10 mo and is most pronounced in the central region of the retina. Our results indicate that retinal pigment epithelial cells are the initial site of insult in GA and that the OAT-deficient mouse is an excellent animal model of GA in human patients.

Animals↗

The directed growth of retinal axons towards surgically transposed tecta in Xenopus; an examination of homing behaviour by retinal ganglion cell axons.

The growth of optic axons towards experimentally rotated tecta has been studied. In stage 24/25 embryos, a piece of the dorsal neural tube, containing the dorsal midbrain rudiment, was rotated through 180 degrees. At later stages of development, the pathways of growing optic axons were investigated by labelling with either horseradish peroxidase or fluorescent dye. It is shown that retinal ganglion cell axons followed well-defined pathways, in spite of the abnormal structure of the brain, and were able to locate displaced tecta. This directed outgrowth of retinal axons in the optic tracts appears to be related either to the tectum or to some other component included in the graft operations. In tadpoles in which the midbrain rudiment was removed, optic axons still followed the normal course of the optic tract. This observation argues against long-range target attraction as being essential in guiding growing retinal axons towards the tectum. An alternative axon guidance mechanism, selective fasciculation, is discussed as a possible alternative to explain the directed axon outgrowth which occurs in both the normal and in these experimentally manipulated tadpoles.

Animals↗

Branch retinal vein occlusion decreases the potential of the inner retinal layer.

To identify the affected retinal layer in cases of branch retinal vein occlusion (BRVO), we analyzed the scotopic electroretinogram (ERG) and electrooculogram (EOG) obtained on the same day in 30 patients with unilateral BRVO. Patients with eye diseases other than unilateral BRVO were excluded. A dome-shaped Ganzfeld illuminator was used for scotopic ERG stimulation and EOG illumination under conventional recording conditions. There was no significant difference in the mean values of scotopic ERG variables between the eyes with BRVO and the normal eyes, but the EOG light peak and L/D ratio were significantly lower in the eyes with BRVO (p < 0.05). However, there was no significant difference between eyes with BRVO and normal eyes regarding the dark through value. Since the light rise potential is induced by background illumination, the low values for light peak and L/D ratio in the eyes with BRVO represent a decrease in the light rise potential compared with that of normal eyes. In addition, since the b wave amplitude of the ERG was normal in the eyes with BRVO, the scotopic ERG and EOG tests suggest that generalized mild hypoxia affects the inner retinal layer of the eyes with BRVO.

Aged↗

Viral resistance and CMV retinitis: design and methods of a prospective study. CRVR Research Groups. Cytomegalovirus Retinitis Viral Resistance Research Group.

A prospective study following a cohort of patients with newly diagnosed, previously untreated cytomegalovirus (CMV) retinitis is being conducted to study drug resistant CMV. Prior to initiation of treatment, patients undergo a baseline eye examination, fundus photography, and blood and urine culture for presence of CMV, and drug susceptibility testing against positive isolates. Patients are followed monthly with a detailed eye examination to diagnose progression of retinitis, and for fundus photography. Cultures are repeated at 1 and 3 months after enrollment, every 3 months thereafter, and at the time of treatment reinduction for the progression of retinitis. This study was designed to determine the prevalence and incidence of drug resistant CMV, as well as risk factors for the development of resistant CMV. It also will determine the correlation between clinical outcome, as measured both by eye examination and fundus photography, and viral resistance.

AIDS-Related Opportunistic Infections↗

The effect of oxygen on retinal degeneration in wild-type and hsp70.1 knockout neonatal retinal degeneration mice.

The present study examined the effect of oxygen on photoreceptor degeneration in the retina of heat shock protein 70.1 (hsp70.1) knockout type and wild-type retinal degeneration (rd) mice. All the neonatal rd mice were exposed to hyperoixa for 5 days after birth, and then were returned to room air before being sacrificed. At the postnatal 10, 14, 18, and 21 days, the ratio of outer nuclear layer (ONL) thickness to total retinal thickness was compared between hsp70.1 knockout type and wild type. The retina was also examined for DNA fragmentation by TdT-mediated biotin-dUTP nick-end labeling (TUNEL). In hsp70.1 knockout type, the ratio of ONL to total retinal thickness was higher than that in the wild type at each time. There was the remarkable difference in the number and distribution of TUNEL-positive cells between hsp70.1 knockout type and wild type rd mice. In conclusion, an oxygen-induced modulation of the rate of photoreceptor degeneration was more marked in the hsp70.1 knockout type than wild type rd mice.

Animals↗

[Sub-retinal fluid interleukin-10 (Il-10) and interleukin-13 (Il-13) concentration in patients with retinal detachment].

PURPOSE: To evaluate the presence of IL-10 and IL-13 in subretinal fluid of patients with rhegmatogenous retinal detachment. MATERIAL AND METHOD: The studies comprised 14 patients on with retinal detachment operated. The presence of cytokines was evaluated using immunoenzymatic assay. RESULTS: IL-10 and IL-13 were found in all subretinal fluid samples. Our results suggest that the presence of IL-10 and IL-13 has the influence on suppression of inflammatory agent release and activity during retinal detachment.

Adolescent↗

Retinal pathology of canine X-linked progressive retinal atrophy, the locus homologue of RP3.

PURPOSE: To describe the course of photoreceptor disease in canine X-linked retinal degeneration. METHODS: Retinas from 55 dogs (44 males, 8 carrier females, 3 homozygous females) were obtained by enucleation under general anesthesia. After fixation and dehydration, tissues were embedded in epoxy resin, sectioned at 1 microm for light microscopy and stained with azure II/methylene blue and a paraphenylenediamine counterstain. For electron microscopy, regions identified by light microscopy were selected and cut at 60 nm. Sections were stained with uranyl acetate-lead citrate. Electroretinography from an additional group of normal males, affected males, and carrier females was performed and the rod and cone responses evaluated. RESULTS: The earliest lesion detectable by electron microscopy was vesiculation of rod discs, followed by disruption of outer segments and death of rods. Loss of cones and progressive atrophy of inner retinal layers followed. Lesions were most severe in the peripheral retina and advanced toward the optic disc with disease progression. Significant variation in disease severity was present in males despite the presence of the same disease allele in all affected dogs. Carrier females displayed generalized reduction in photoreceptor density as well as multifocal areas of complete rod loss. The electroretinogram (ERG) findings were compatible with the histopathologic abnormalities. Homozygous females had lesions similar to those seen in affected males. CONCLUSIONS: X-linked retinal degeneration is characterized by initial degeneration of rod photoreceptors, followed by loss of cones and progressive atrophy of the inner retina. Carrier females display a phenotype consistent with random X-chromosome inactivation. Variation in genetic background may alter expression of the disease allele in affected animals, thus accounting for variation in phenotypic expression of the disease.

Animals↗

[An electron microscopic study of retinal development and pathogenesis in mutant CBA/J mice with hereditary retinal degeneration].

Electron microscopic study of the neural retina pathogenesis was carried out on mice CBA/J in comparison with corresponding process in substrain CBA/Ki (Caley et al., 1972). A difference in terms of the pathology development was found between substrains CBA/J and CBA/Ki. It was shown that, in CBA/J, the retinal degeneration begins later than in CBA/Ki. As distinct from the latter, CBA/J proceeds to increase the thickness of outer nuclear and plexiform layers as well as the number of membranous discs of rod outer segments (ROS) between P10 and P12. In the retina of mouse CBA/J, pathologic alterations of the outer nuclear layer and the inner segments of photoreceptors precede the ROS destruction. It was found that the pigment epithelium is capable to phagocytize membranous discs of ROS in mouse CBA/J at P10 and P12. In CBA/J, the mitochondria in inner segments of photoreceptors begin to decay at P10; by P12, the amount of such segments reach 40%. At P12, the number of pycnotic nuclei (6%) in the outer nuclear layer coincides with the number of inner segments with dense degenerative cytoplasm. At P15, the state of retina as evaluated by the extent of far advanced degeneration of the outer nuclear layer is equalized in mice of both substrains. From P10 to P15, macrophages which phagocytize membranous discs of ROS are present in the interphotoreceptor space of CBA/J. The administration of PABA solution (7.5 x 10(-3) mg/g) daily from P1 to P9 or from P1 to P11 and with subsequent fixation at P10 and P12 respectively exerted no effect on the rate of retinal pathogenesis in mouse CBA/J. The causes of revealed differences in the development of retinal pathology between CBA/Ki and CBA/J are discussed as well as the causes of the absence of PABA effect on the retina of mutant mouse CBA/J.

4-Aminobenzoic Acid↗

Activated retinitis pigmentosa peripheral lymphocytes adhere to and alter cultured human retinal pigment epithelial cells.

Interleukin-2 receptor (IL-2R) is an activation molecule that, when expressed on peripheral blood lymphocyte (PBL) membranes, indicates the secretion of IL-2 and initiation of an immune system activation cascade. Comparing the average of IL-2R expression in 34 patients with retinitis pigmentosa (RP) syndrome (561 +/- 282 cells/mm3; mean +/- standard deviation) with 35 age-matched normal subjects (194 +/- 39 cells/mm3), it was found that those with RP had greater numbers of IL-2R-positive cells (P less than 0.001). The increased amounts of IL-2R on PBL of 29 RP and the homotypic self-aggregation of RP PBL by phase and scanning electron microscopy led to the study of the interaction of RP PBL with cultured human postmortem retinal pigment epithelial cells (RPE). A direct correlation was found between the amount of IL-2R expression and the numbers of RP lymphocytes adhering to RPE monolayers. However, the adherence effect was not unique to RP syndrome but appeared to be a nonspecific result of lymphocyte activation. Greater adherence to RPE than normal also was observed in PBL from disease control subjects with elevated IL-2R values and in PBL stimulated by the mitogen, concanavalin A (Con-A). In addition, RPE monolayers were destroyed by Con-A-stimulated PBL that showed 95-98% IL-2R expression. Similar, but less serious effects, occurring in RPE cells after 1 wk's cocultivation with RP PBL, suggested that activated RP lymphocytes can be cytotoxic to RPE during prolonged contact. Because macrophage-like cells and class II major histocompatibility complex expression have been found in RP-affected retinas, immune-mediated cytopathologic effects may contribute to retinal degeneration in RP.

Adolescent↗

Cases from the aerospace medicine residents' teaching file. Case #38. A navigator with nonischemic central retinal vein occlusion progressing to ischemic central retinal vein occlusion.

A case report of a young USAF navigator with nonischemic central retinal vein occlusion progressing to ischemic central retinal vein occlusion is presented. This young man was treated with hyperbaric oxygen therapy early in the course of his disease with complete resolution of his condition. Two years later his vision remained 20/17. This is the first known case of central retinal vein occlusion being treated with hyperbaric oxygen.

Adult↗

Altered glycoconjugates in cultures of retinitis pigmentosa retinal pigment epithelium.

These studies have shown that these are some alterations in the complex carbohydrates associated with the cell surface of RPE cells from donors with dominant retinitis pigmentosa. Differences are found both in proteoglycans and in glycoproteins. Proteoglycans of different sizes and glycosaminoglycan composition are associated with distinct cellular compartments of normal RPE cells. In the case of dominant retinitis pigmentosa studied here, there are some alterations in RPE proteoglycans. Within a given cellular compartment, there may be differences in the size distribution and/or the ratios of the proteoglycan size classes. In addition, there may be altered glycosaminoglycan content found between peaks of comparable size. There also appears to be more microheterogenity in oligosaccharides derived from surface glycoproteins of retinitis pigmentosa RPE cells. This may be due to differences in the total number of carbohydrate units or in the organization of the branching structure as suggested by altered size distribution and lectin-reactivity, respectively. While the reason for these differences is not clear, they could be due to abnormal processing and/or increased degradation. Considering their importance, alterations in cell surface glycoconjugates could affect the ability of RPE cells to interact with their environment and to maintain a healthy status.

Adult↗

Surgical techniques for giant retinal tears with retinal tacks.

In order to repair an inverted retinal flap on the choroid in case of retinal detachment with giant tears, the authors have developed a retinal tack made of acetalcopolymerisate. The tack is very durable and should remain inactive in the human body, owing to its stability under conditions of heat, alkali and acid. Manipulating the tack is adequately easy; the procedure and the tacks themselves appear to be well tolerated by the eye. The detailed design of the tack and its method of use are described in this report.

Adolescent↗

Experimental autoimmune uveo-retinitis and specificity of retinal antigens.

Chorio-retinal lesions induced in guinea pigs after one inoculation of bovine rod outer segments (ROS) with complete Freund's adjuvant are described with light and electron microscopy. The auto-antigenic activity of different preparations from bovine retina and uvea is compared for their efficacy to induce the disease. ROS are much more active than total retina homogenate. Pigment epithelium is active, and the effect of choroid is impaired after removal of pigment epithelium from the surface of the choroid. Purification of ROS by several sucrose flotations does not reduce their activity. Almost complete extraction of soluble antigens from pure ROS by buffer washings, controlled with isoelectrofocusing and immunodiffusion, decreases only slightly their pathogenicity. Rhodopsin, extracted using cetyltrimethylammonium bromide from pure washed ROS, induced prominent chorio-retinal damage at the dose of 500 mug. It seems likely that besides soluble retinal auto-antigens, outer segments contain a pathogenic insoluble antigen which seems to be linked to rhodopsin or to be rhodopsin itself.

Animals↗