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PubMedDate not supplied

Retinal S antigen reactivity in patients with retinitis pigmentosa and Usher's syndrome.

Cell-mediated immunity to retinal antigens as determined by in vitro assays has been detected in a variety of retinal degenerative and retinal destructive conditions. The authors studied the in vitro reactivity to the soluble retinal S antigen of peripheral blood mononuclear cells from patients with simplex and multiplex retinitis pigmentosa (RP) and Usher's syndrome along with normal controls. The cellular stimulation index (SI) was calculated by comparing 3H-thymidine incorporation in cells exposed to either purified S antigen, crude whole human retinal antigen, or human choroidal antigen with that in unstimulated control cultures. Eight of 15 patients with RP and 5 of 6 with Usher's had a SI greater than the tolerance limits of normal values. These results indicate that the immune system may be involved either primarily or secondarily in RP.

Adolescent↗
PubMed2004

Effects of indocyanine green on the retina and retinal pigment epithelium in a porcine model of retinal hole.

PURPOSE: This study was designed to emulate human macular hole surgery and to test the effects of indocyanine green (ICG) on the retina and retinal pigment epithelium (RPE). METHODS: Yorkshire Cross pigs (n = 23) underwent vitrectomy, separation of the posterior cortical vitreous, and creation of a single retinal hole. In three study groups (n = 6, each group), air-fluid exchange was performed, following which balanced salt solution (BSS), 1.0% ICG, or 0.5% ICG was applied over the retinal hole. In one additional group (n = 5), 0.5% ICG was injected into the fluid-filled eye. At 4 weeks, the eyes were examined clinically, and fundus photographs were obtained before enucleation and light microscopic examination. RESULTS: Clinical evaluations documented a statistically significant difference between study groups (P = 0.036). There was a higher rate of moderate or severe RPE atrophy among animals where 1% or 0.5% ICG was applied in air-filled eyes (83% and 67%, respectively) compared with BSS controls (17%) and fluid-filled eyes receiving 0.5% ICG (40%). Histologic evaluation demonstrated a statistically significant difference between groups (P = 0.044), with extensive outer retinal degeneration observed in air-filled eyes receiving 1% or 0.5% ICG (66% and 60%, respectively) compared with BSS controls or fluid-filled eyes receiving 0.5% ICG (none of the eyes in either group). None of the study groups had any changes in the inner retina except at the retinal hole site. CONCLUSIONS: Retina exposed to ICG concentrations used in human vitreoretinal surgery had greater RPE atrophy and outer retinal degeneration than control eyes undergoing the same surgery without ICG. Eyes filled with infusion fluid during ICG injection had less damage to the RPE and outer retina than did air-filled eyes receiving ICG.

Air↗
PubMed1981

Relationship of cystic retinal tufts to retinal detachment.

The histologic and gross pathologic features of cystic retinal tufts are reviewed, and the clinical characteristics of this lesion described. A survey of 200 retinal detachments revealed that cystic retinal tuft was the precipitating lesion for the detachment in from 6.5 to 10% of cases. Since the prevalence of cystic retinal tuft is 5%, the risk of such a lesion leading to retinal detachment was computed to be from 0.18 to 0.28%, and for this reason prophylactic treatment of cystic retinal tufts is not advised.

Adult↗
PubMed2005

Infection of retinal neurons during murine cytomegalovirus retinitis.

PURPOSE: Previous results suggest that retinal neurons are infected early during murine cytomegalovirus (MCMV) infection of the inner retina. The purposes of this study were to identify which retinal neurons are infected and to determine the routes by which MCMV spreads in the retina. METHODS: Immunosuppressed (IS) BALB/c mice were inoculated with 5 x 10(3) PFU of MCMV (k181) through the supraciliary route. Injected eyes were collected at several times after inoculation, sectioned, and examined by electron microscopy and by staining for retinal cell antigens and for MCMV early (EA) or late (LA) antigen. RESULTS: MCMV-infected cells were observed in the choroid and RPE by day 3 after infection (PI) and in the inner retina beginning at day 5 PI. At this time, many horizontal and bipolar cells were MCMV-antigen-positive but only rare MCMV-infected amacrine cells (glycine positive or gamma-aminobutyric acid [GABA] positive) or MCMV-infected ganglion cells (NF positive) were observed in the inner retina. At day 10 PI, most virus-infected cells were glial fibrillary acidic protein (GFAP)- and GABA-positive glia. Virions were observed by electron microscopy in the choroid, RPE, and inner nuclear layer of the retina. Although virions were observed in the endothelium of the retinal vessels and the nearby retinal cells, the endothelial cell lining of the retinal vessels remained intact. Both apoptotic cells and necrotic cells were seen in the inner retina. CONCLUSIONS: In the inner retina, horizontal and bipolar cells were the early (< or = day 7 PI) targets of MCMV infection. Virus spread from the RPE and the photoreceptor layer to the inner retina through infected Muller cells and within the inner retina horizontally through infected horizontal cells.

Animals↗
PubMed2001

Does glaucoma medication influence the diameter of the retinal arteriole in the human eye? (A pilot study using the retinal vessel analyser).

PURPOSE: To investigate the potential in vivo influence of different topical glaucoma medications on the diameter of the retinal arterioles of healthy volunteers and glaucoma patients. METHODS: The diameter of one pre-selected retinal arteriole per eye was measured using the Retinal Vessel Analyser (RVA), an instrument developed for non-invasive clinical measurement of the diameter of the main retinal vessels. The instrument contains a video system, and the integrated software recognises the boundaries of the retinal vessels by detecting their light-transmission profile. The vessel diameter (in arbitrary units) is plotted against time (seconds) on a separate display screen. In Study I the vessel diameter was measured in 12 eyes of six healthy volunteers (age 21-26 years, mean age 24.0 years) on six occasions each separated by 14 days. In a double-masked fashion, each subject's right eye was treated with one of 5 glaucoma medications (brinzolamide 1%, timolol 0.5%, betaxolol 0.5%, brimonidine 0.2% or latanoprost 0.005%) and the left eye always received balanced salt solution. In Study II, one randomly selected eye of 16 patients (age 50-79 years, mean age 65.2 years) suffering from primary open-angle glaucoma controlled with topical monotherapy was investigated, in an unmasked fashion. Four patients were on betaxolol 0.5% treatment, six subjects were receiving non-selective topical beta receptor blockers and six subjects were being treated with once daily latanoprost 0.005%. RESULTS: The coefficient of variation for the arteriole diameter in the healthy volunteers was less than 12% in each case. No significant post-treatment change of the diameter of the pre-selected arteriole was found for any topical medication investigated, either in the healthy volunteers (Study I) or in the patients suffering from glaucoma (Study II) (p>0.05, paired t-test). In addition, in Study I no difference was observed in the alteration of the arteriole diameter between the baseline and the hour 2 measurements when the values from the drug-treated and placebo treated eyes were compared (p>0.05, two-way ANOVA). CONCLUSION: In the present investigations it was not possible to detect any statistically meaningful change of the arteriole diameter at two hours after the instillation of any of several topical antiglaucoma drugs widely used in clinical practice. Further investigations are necessary to clarify whether the lack of observed change is due to the lack of retinal vascular effects of the drugs investigated, or is due to an inability of the RVA instrument in practice to detect alterations between time-points separated by several hours.

Adrenergic alpha-Antagonists↗
PubMed2005

Adeno-associated viral vectors for retinal gene transfer and treatment of retinal diseases.

Retinal gene transfer holds big promises for the treatment of inherited and non-inherited blinding diseases, such as retinitis pigmentosa or age-related macular degeneration. Key to the development of successful gene-based therapies for the eye are efficient tools for retinal gene transfer. Vectors based on adeno-associated viruses (AAV) are able to transduce robustly and persistently different retinal cell types of animal models after a single intraocular administration. Recombinant AAV (rAAV) vectors are versatile gene transfer tools in that capsid proteins from dozens of AAV serotypes can be easily interchanged, resulting in the creation of recombinant vectors with unique transduction properties. This has allowed successful proof-of-principle studies using rAAV-mediated gene transfer to restore retinal morphology and function in small and large animal models of retinal diseases. In addition, gene delivery using rAAV vectors in the eye seems to have appropriate biosafety characteristics to rapidly move it from bench to bedside. All the above aspects will be reviewed and discussed in detail below.

Angiogenesis Inhibitors↗
PubMed2006

[National survey on vitreo-retinal surgery and the management of rhegmatogenous retinal detachments in Spain. Project retina 2].

PURPOSE: To obtain information throughout Spain on the current management of vitreo-retinal surgical diseases, the number of ophthalmologists involved in retinal surgical diseases care, and the urgent management of retinal detachments. METHODS: A 30 item questionnaire was sent by mail, on two separate occasions, to the heads of Ophthalmology Departments of 276 centers in Spain. RESULTS: A total response rate of 48.2% was achieved, however the answers from private centers represented only 9.4% of the total so these were excluded from the analysis. The centers most likely to respond were those in Teaching Hospitals (TH) (52.3%). Of these, 64% of hospitals responded that, in the last year, they performed pars plana vitrectomies (PPV) and 70% performed more than 100 PPVs in the year. In all, 77% of the centers that performed PPVs had also performed them urgently. A total of 75% of hospitals indicated that they had ophthalmologists mainly dedicated to retinal diseases care, with a median of 2 specialists per center, with this representing 23% of their total staff. Retinal surgery was performed by general ophthalmologists in 11.5% of centres. Only 40.3% of hospitals audit their results (37.5% TH). CONCLUSIONS: Despite the existence of a relatively low response rate, as well as some biases and methodological problems, data on the management of retinal surgical disease has been obtained for the first time at a national level. This data will facilitate later studies and must be taken into consideration in improving the planning and adequate management of these diseases in Spain.

Humans↗
PubMed2000

Slit inhibition of retinal axon growth and its role in retinal axon pathfinding and innervation patterns in the diencephalon.

We have analyzed the role of the Slit family of repellent axon guidance molecules in the patterning of the axonal projections of retinal ganglion cells (RGCs) within the embryonic rat diencephalon and whether the slits can account for a repellent activity for retinal axons released by hypothalamus and epithalamus. At the time RGC axons extend over the diencephalon, slit1 and slit2 are expressed in hypothalamus and epithalamus but not in the lateral part of dorsal thalamus, a retinal target. slit3 expression is low or undetectable. The Slit receptors robo2, and to a limited extent robo1, are expressed in the RGC layer, as are slit1 and slit2. In collagen gels, axon outgrowth from rat retinal explants is biased away from slit2-transfected 293T cells, and the number and length of axons are decreased on the explant side facing the cells. In addition, in the presence of Slit2, overall axon outgrowth is decreased, and bundles of retinal axons are more tightly fasciculated. This action of Slit2 as a growth inhibitor of retinal axons and the expression patterns of slit1 and slit2 correlate with the fasciculation and innervation patterns of RGC axons within the diencephalon and implicate the Slits as components of the axon repellent activity associated with the hypothalamus and epithalamus. Our findings suggest that in vivo the Slits control RGC axon pathfinding and targeting within the diencephalon by regulating their fasciculation, preventing them or their branches from invading nontarget tissues, and steering them toward their most distal target, the superior colliculus.

Animals↗
PubMed1988

EB-virus transformed human lymphocytes from uveitis and retinitis pigmentosa patients secrete antibodies to retinal antigens.

Autoimmunity to retinal antigens has been implicated in the pathogenesis of both endogenous posterior uveitis and retinitis pigmentosa. Recent studies, however, suggest that low levels of antibodies to retinal antigens occur generally in the population. We have attempted to maximize antibody secretion by peripheral blood lymphocytes from patients and normal healthy controls using the polyclonal activator, Epstein-Barr virus, to stimulate lymphocytes in vitro. Whereas cells from controls and uveitis patients showed a level of anti-retinal antibody secretion which corresponded with their serum titres of antibodies, patients with retinitis pigmentosa showed a greater tendency to produce high secretor lymphocytes after EB-virus stimulation despite having low serum titres of antibody. This strategy for studying antibody secretion may be of value in unmasking low levels of autoimmune responsiveness in conditions such as retinitis pigmentosa where low grade tissue damage occurs over many years and antigen release is correspondingly too low to initiate a measurable autoimmune reaction.

Autoantibodies↗
PubMed1988

The relationship between refractive errors and retinal detachment--analysis of 1,166 retinal detachment cases.

We compared 1,166 eyes with retinal detachment to 11,671 eyes of patients without retinal detachment in order to clarify the distribution of refraction ranges and the relative frequency in incidence of retinal detachment for each range. In the retinal detachment group, hyperopia was detected in 8.58%, emmetropia in 9.26% and myopia in 82.16%, and the corresponding ratios in the control group were 24.29%, 41.30% and 34.41%, respectively. The retinal detachment group thus exhibited a high frequency of myopia, as has been known. The relative frequency of retinal detachment for each range of refraction was 0.35 for hyperopia, 0.22 for emmetropia and 0.83 for myopia in the range -0.75 to -2.75 D. The relative frequency increased with an increase of severity in myopia up to the range of higher than -15.0 D, where the frequency was 68.6 times higher than for the hyperopic range.

Adolescent↗
PubMedDate not supplied

Syphilitic retinitis. A cause of necrotizing retinitis.

A healthy-appearing male patient presented with signs of unilateral fibrinous iritis, necrotizing retinitis, retinal vasculitis, and vitritis, suggestive of a herpesvirus retinitis or acute retinal necrosis syndrome (ARN). The patient, an active homosexual, withheld the details of his sexual history, portraying himself as exclusively heterosexual. With the exception of a positive VDRL and FTA-ABS, the workup was negative. Examination of the cerebrospinal fluid confirmed the presence of neurosyphilis. The patient was successfully treated with intravenous penicillin, which resulted in a complete visual recovery. Syphilitic retinitis must be considered in evaluating patients with necrotizing retinitis.

Adult↗
PubMed1980

Immune reactivity to different retinal antigens in patients suffering from retinitis pigmentosa.

The immune status of patients suffering from different types of retinitis pigmentosa has been investigated. The lymphocytes of these patients could be stimulated by incubation with human soluble retinal antigens as well as with bovine rod outer segments. The results suggest the involvement of the cellular immune system in retinitis pigmentosa. The leukocyte migration inhibition test also pointed in that way, especially if bovine rhodopsin was used as the antigen. The complement fixation test suggested the presence of a nonspecific weak antibody activity in the blood of retinitis pigmentosa patients as well as of controls. This activity seemed predominantly to be directed to the insoluble fraction of human retinas. On the basis of the findings we conclude that patients suffering from retinitis pigmentosa may become sensitized to retinal antigens, especially to those localized in the rod outer segments. This sensitization concerns the cell-mediated immune system and seems not to be correlated with a special type of the disease.

Adolescent↗
PubMed1982

[Treatment of retinal detachment associated with large or giant retinal tears (author's transl)].

Nineteen retinal detachments associated with large or giant retinal tears (70 degrees to 340 degrees) were treated by a microsurgical technique excluding vitrectomy. Reattachment of the retina was achieved in 15 patients (79 p. cent). Near normal visual acuity was achieved in 9 eyes. The anatomical and visual results achieved in this series lead the authors to discuss the specific problems involved in the treatment of retinal detachments associated with large or giant retinal tears. The indications for vitrectomy can be limited to those retinal detachments associated with a retinal tear involving more than 2 quadrants, and/or an inverted posterior margin reaching or covering the posterior pole, and/or a fixed retina and/or massive retraction of the anterior vitreous gel. In the clinical experience of the authors the cases which do not fulfil the previous criteria can be treated by a microsurgical technique excluding vitrectomy.

Adolescent↗
PubMed1993

[Peripheral retinal correspondence after retinal detachment].

BACKGROUND: Occasionally, patients who underwent surgery for complicated retinal detachment report spatial distortions. This may be due to a translocation of photoreceptors when they become reattached to the pigment epithelium. We wanted to find out if, and to what extent, similar translocations occur after a simple buckling operation. METHODS: Binocular retinal correspondence was used as an indicator of photoreceptor translocation. Correspondence was measured in the peripheral visual field at eccentricities of 5, 10 and 20 degrees, using a mirror haploscope. We examined two normal observers, one patient having had surgery for complicated retinal detachment including retinotomy, and 23 patients who had simple radial buckling operations. RESULTS: The patient who had received complicated detachment surgery including retinotomy revealed a tremendous shift in correspondence. Of the 23 patients who had simple radial buckle operations, only 10 were able to sustain central fixation while being tested in the periphery. Of these 10 patients, 2 showed distortions of peripheral retinal correspondence in the area of previous retinal detachment. However, only one of them remembered some spatial distortion after surgery. CONCLUSION: As a rule, photoreceptors become correctly reattached after radial buckle operations for retinal detachment. Rarely, vertical or horizontal translocations of about 1 to 2 degrees occur, but this does not usually lead to metamorphopsia.

Adult↗
PubMed1996

Inhibition of retinal pigment epithelial cell-induced tractional retinal detachment by disintegrins, a group of Arg-Gly-Asp-containing peptides from viper venom.

PURPOSE: Integrin-mediated extracellular matrix (ECM) attachment plays an important role in vitreous contraction of retinal pigment epithelial (RPE) cells. Disintegrins, a group of Arg-Gly-Asp (RGD)-containing peptides from viper venom, are potential anti-adhesion agents that interfere with integrin-ECM binding. This study was performed to determine whether disintegrins were effective in inhibiting RPE cell-induced matrix attachment in vitro and tractional retinal detachment in a rabbit model in vivo. METHODS: Two disintegrins, echistatin from viper Echis carinatus and flavoridin from Trimeresurus flavoviridis, were used. The expression of integrins on the surface of bovine and rabbit RPE cells was examined by indirect immunofluorescent stain with specific anti-integrin monoclonal antibodies. The inhibitory effect of disintegrins on RPE cell-mediated ECM attachment and vitreous contraction was evaluated with cell adhesion and vitreous contraction assays. In the in vivo model, rabbit eyes were injected intravitreously with either homologous rabbit RPE cells alone or together with disintegrins to induce tractional retinal detachment. The cytotoxic effect of disintegrins was examined with a cell proliferation assay using the alamar blue method. Retinal toxicity of disintegrins was evaluated with electroretinograms and histologic examination of the rabbit eyes. RESULTS: Bovine and rabbit RPE cells showed the positive staining for the integrins alpha 2 beta 1 and alpha 5 beta 1 on cell surface. Disintegrins, echistatin, and flavoridin inhibited RPE cell attachment to the ECM. The potency of disintegrins was 150 to 300 times higher than that of Gly-Arg-Gly-Asp-Ser (GRGDS) peptide. The disintegrins also inhibited RPE cell-induced vitreous contraction in a dose-dependent manner, whereas the GRGDS peptide had no effect. In the in vivo experiment, echistatin (50 microgram/ml) or flavoridin (80 microgram/ml) significantly inhibited RPE cell-induced tractional retinal detachment compared with the control group at week 2 (P< 0.05) and week 4 (P< 0.01) after surgery. Disintegrins were nontoxic to RPE cells and rabbit retina as evaluated by cytotoxicity tests, electroretinograms, and histologic examinations. CONCLUSIONS: The disintegrins were effective in inhibiting RPE cell attachment to the ECM and vitreous contraction in vitro. They also were effective in suppressing RPE cell-induced tractional retinal detachment in the rabbit eyes. They were nontoxic. Disintegrins and their analogs might be potential anti-adhesion therapeutic agents in the treatment of proliferative vitreoretinopathy.

Amino Acid Sequence↗
PubMed1989

New and previously unidentified retinal breaks in eyes with recurrent retinal detachment with proliferative vitreoretinopathy.

The location of retinal breaks found on preoperative examination was studied in 68 eyes of 68 patients with recurrent retinal detachment and proliferative vitreoretinopathy. Twelve eyes had 23 open breaks that were known to exist previously, no open break was detected in 18 eyes, and 72 new or previously unidentified breaks were found in 41 eyes. Forty-seven (65.3%) of the 72 breaks were located on previous buckles, and 31 of these were on the posterior slope of the buckle. Twenty-nine (40.2%) of all new or previously unidentified breaks were on the border of a cryopexy-induced chorioretinal scar, and of these, 25 breaks (86%) were on the posterior slope of the buckle. Our results indicate that the retina that borders chorioretinal scars is vulnerable and prone to develop retinal tears secondary to traction from preretinal membranes. The vicinity of cryopexy-induced scars should be closely observed for retinal breaks in cases of recurrent retinal detachment with proliferative vitreoretinopathy.

Choroid↗
PubMed1996

Retinal venous sheathing and the blood-retinal barrier in multiple sclerosis.

OBJECTIVE: To assess the temporal relations among retinal appearance, disruption of the blood-retinal barrier, clinical subgroup, disease course, and disruption of the blood-brain barrier in multiple sclerosis. DESIGN: A 6-month prospective study involving monthly clinical ocular examinations, color fundus photography, fundus fluorescein angiograms, and magnetic resonance brain scans with gadolinium-diethylenetriamine-pentaacetic acid (Gd-DPTA) enhancement. SETTING: University-based ophthalmology and neurology departments. PATIENTS: Twenty-three patients with relapsing-remitting, primary-progressive, or secondary-progressive multiple sclerosis. RESULTS: Retinal venous sheathing was seen in six patients. The appearances observed included focal venous sheathing, diffuse venous sheathing, sheathing centered on sites of arteriovenous crossover, and focal perivenous hemorrhage. Arteriolar sheathing was also observed in one patient. Venous leakage on fundus fluorescein angiogram was detected in three patients, all of whom also had sheathing. The following three patterns of disruption of the blood-retinal barrier were seen on fundus fluorescein angiogram: focal leakage, extensive leakage, and very late wall staining. In one patient, the leakage was transitory. No correlations were observed between ophthalmologic features and multiple sclerosis clinical subgroup, disease course, or the number of new (Gd-DTPA-enhancing) lesions on magnetic resonance imaging. CONCLUSIONS: Disruption of the blood-retinal barrier, like the more frequent disruption of the blood-brain barrier seen on magnetic resonance imaging, is often unrelated to clinical neurologic relapses and occurs with apparently similar frequency in different patients independent of clinical disease course.

Adult↗
PubMed1986

Experimental retinal vascular occlusion. II. A clinico-pathologic correlative study of simultaneous occlusion of central retinal vein and artery.

After experimentally occluding the central retinal vein and artery simultaneously at their point of entry into the optic nerve, acute retinal necrosis occurred, but not hemorrhagic retinopathy. In the retinal vasculature, stagnation of blood flow and thrombosis with subsequent recanalization was noted. The necrosis was extensive in the inner retinal layers but focal in the outer retinal layers. The internal limiting membrane was detached and disrupted in every case. Following the post-edematous stage, numerous micro and macroretinal cysts appeared. The peripheral retina showed much less ischemic changes. A clinico-pathologic correlation was made.

Animals↗