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PubMed1992

Reciprocal retinal transplantation: a tool for the study of an inherited retinal degeneration.

The pathogenesis of retinal degeneration in rd mutant mice has been extensively studied, the gene responsible for the defect has been cloned, and the neural retina has been identified as the primary site for the degeneration. However, the possible contributory role of the ocular environment in this form of retinal degeneration remains undetermined. Retinal transplantation, which provides the opportunity to implant the neural retinal into a genetically defined intraocular environment, was used to examine this possibility. A reciprocal retinal transplantation paradigm was designed based on three experimental groups: (1) normal immature retina transplanted into rd/rd mutant eyes, (2) rd/rd immature retina transplanted into normal eye, and (3) normal immature retina transplanted into normal eyes. The rates of survival and histological characteristics of the grafts were compared between the three groups. At post-transplantation Day 3 (PTD 3), there were no differences between the three groups. Between PTD 10 and 15, the retinal grafts in group 1 showed degeneration. In contrast, the retinal grafts in groups 2 and 3 survived and developed well. At PTD 30, the retinal grafts in both groups 1 and 2 showed degeneration, but the retinal grafts in group 3 survived and remained differentiated well. These results suggest that the retinal degeneration of rd mice may be caused by both a deficit of the neural retina and intraocular environmental changes which are elicited either as a result of mutation or as a sequel to retinal degeneration.

Animals↗

PubMed2005

Spontaneous patterned retinal activity and the refinement of retinal projections.

A characteristic feature of sensory circuits is the existence of orderly connections that represent maps of sensory space. A major research focus in developmental neurobiology is to elucidate the relative contributions of neural activity and guidance molecules in sensory map formation. Two model systems for addressing map formation are the retinotopic map formed by retinal projections to the superior colliculus (SC) (or its non-mammalian homolog, the optic tectum (OT)), and the eye-specific map formed by retinal projections to the lateral geniculate nucleus of the thalamus. In mammals, a substantial portion of retinotopic and eye-specific refinement of retinal axons occurs before vision is possible, but at a time when there is a robust, patterned spontaneous retinal activity called retinal waves. Though complete blockade of retinal activity disrupts normal map refinement, attempts at more refined perturbations, such as pharmacological and genetic manipulations that alter features of retinal waves critical for map refinement, remain controversial. Here we review: (1) the mechanisms that underlie the generation of retinal waves; (2) recent experiments that have investigated a role for guidance molecules and retinal activity in map refinement; and (3) experiments that have implicated various signaling cascades, both in retinal ganglion cells (RGCs) and their post-synaptic targets, in map refinement. It is likely that an understanding of retinal activity, guidance molecules, downstream signaling cascades, and the interactions between these biological systems will be critical to elucidating the mechanisms of sensory map formation.

Animals↗

PubMed2005

Vitreous and retinal amino acid concentrations in experimental central retinal artery occlusion in the primate.

PURPOSE: Vitreous and retinal amino-acid concentrations were evaluated in a primate model of central retinal artery occlusion (CRAO) to study the role of glutamate excitotoxicity in acute retinal ischaemia. METHODS: Unilateral, acute CRAO was produced by temporary clamping of the central retinal artery for 190 min in four elderly rhesus monkeys. Fundus photography, fluorescein angiography, and electroretinogram were performed before and during CRAO, and after unclamping the artery. Vitreous samples were obtained before and after CRAO in both eyes, and analysed for 13 amino-acid concentrations using high-pressure liquid chromatography. The animals were killed 350 min after retinal reperfusion, and the retinal tissue was submitted for amino-acid analysis. RESULTS: In all four eyes, the macula showed the 'cherry red spot'. The CRAO was confirmed by fluorescein angiography and decreased b-wave on electroretinogram. Retinal histology confirmed ischaemic changes in the inner retina. Changes in all 13 vitreous amino-acid concentrations after CRAO (including glutamate) were not significantly different between study and control eyes (P = 0.09 to 0.82). All retinal amino-acid concentrations (including glutamate) were not significantly different between two eyes (P = 0.07-0.93). CONCLUSIONS: In the primate model of acute inner retinal ischaemia induced by transient CRAO, we were unable to detect significantly elevated concentrations of vitreous and retinal glutamate. Our primate model has the advantage of closely modelling the CRAO in humans. Further basic and clinical studies are needed to elucidate the role of glutamate excitotoxicity in retinal ischaemia.

Acute Disease↗

PubMed2001

Retinal fixation of traumatic retinal detachment with metallic tacks: a case report with 10 years' follow-up.

BACKGROUND: Retinal rupture and detachment caused by traumatic ocular perforation has a poor prognosis without extensive repair procedures. The authors describe the phases of treatment of a complex injury in a 21-year-old man with a traumatic retinal rupture in whom metallic tacks were used for retinal fixation. The report does not include histopathology. METHODS: Observational case report and literature review. The outcome of a 10-year follow-up is evaluated at the latest visit by determining the visual acuity (VA) and by observing the state of retina and tacks. RESULTS: A traumatic retinal rupture with detachment was treated with titanium tacks for retinal fixation. By inserting a total of 13 metallic tacks for the repair of a temporal postequatorial retinal rupture and adjacent retinal detachment a successful outcome was achieved. Two additional operations were performed to reattach the retina of nasal hemisphere in the same eye. One dislodged tack was removed at the final operation. Ten years later, at the last intervention, VA was 12/20 in the injured eye. The retina was completely attached, and the remaining 12 tacks were in place, although six of them were partially pushed up by an encircling band. Proliferative vitreoretinopathy (PVR) was absent, and a relatively narrow circumferential zone of scar tissue adjacent to the row of tacks was visible. The patient occasionally experienced glare in the affected eye, but was otherwise symptom-free. CONCLUSION: Reports of long-term experiences with mechanical retinal refixation with metallic tacks are scarce. Especially in extended use, the tacks are claimed to cause several complications, including PVR. Although modern ophthalmic surgery offers a variety of methods for retinal reattachment, the complexity of the damage caused by trauma may lead to a dead end in refixation attempts. Nevertheless, retinal tacks may represent an adjunctive remedy in complex retinal detachment cases.

Adult↗

PubMed2000

A retinal-derived relaxing factor mediates the hypoxic vasodilation of retinal arteries.

PURPOSE: To investigate the mechanisms involved in hypoxic vasodilation using an in vitro setup. METHODS: Retinal arteries with and without retinal tissue were mounted on a wire myograph. The segments were contracted with prostaglandin (PG)F(2alpha) (30 microM) or 120 mM K(+). Hypoxia was induced by replacement of O(2) by N(2) in the gas used to bubble the Krebs-Ringer bicarbonate organ bath solution. RESULTS: Hypoxia induced complete relaxation of preparations with adherent retinal tissue contracted with PGF(2alpha). Preparations without retinal tissue were not affected by the change in oxygenation. When the retinal arteries were contracted with 120 mM K(+), hypoxia no longer induced relaxation of the preparation with adherent retinal tissue. The presence of an NO-synthase inhibitor (L-NA, 0.1 mM), a cyclooxygenase inhibitor (indomethacin, 50 microM), or an adenosine receptor antagonist (8-sulfophenyltheophylline, 1 mM) did not affect hypoxic vasodilation. Excitatory amino acids and lactate had no or only a limited effect on the PGF(2alpha)-induced contraction and are therefore unlikely mediators of hypoxic vasodilation. HCl (10 mM) reduced the pH to 6.1 +/- 0.08 (n = 4) and induced a pronounced but transient relaxation of the retinal artery contracted with PGF(2alpha) or 120 mM K(+), whereas hypoxia induced relaxation of the retinal artery contracted with PGF(2alpha) only in the presence of adherent retinal tissue. CONCLUSIONS: Adherent retinal tissue mediates the hypoxic vasodilatation of bovine retinal arteries in vitro. Neither NO, prostanoids, adenosine, excitatory amino acids lactate or changes in pH seem to be involved in this hypoxic response.

Animals↗

PubMed1992

Biosynthesis of all-trans-retinoic acid from retinal. Recognition of retinal bound to cellular retinol binding protein (type I) as substrate by a purified cytosolic dehydrogenase.

An NAD-dependent rat liver cytosolic dehydrogenase accepted as substrate retinal generated in situ by microsomes from retinol bound to excess CRBP (cellular retinol binding protein, type I). This activity, which was not retained by anion-exchange chromatography at pH 9.15, was designated P1. P1 activity increased 2.5-fold, with no statistically significant change in its K or Hill coefficient, in liver cytosol from rats fed a retinoid-deficient diet. Orally dosed retinoic acid partially suppressed the increase. Activities chromatographically similar to hepatic P1 were observed in cytosols from rat kidney and testes. P1, purified from rat liver cytosol, had a pI of approximately 8.3, migrated as a tetramer (214 kDa) on a Sephadex G-200 column, and had a subunit molecular mass of 55 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With free retinal it catalyzed a maximum rate of retinoic acid synthesis of 265 nmol/min/mg of protein and exhibited allosteric kinetics with a K of 0.76 +/- 0.35 microM and a Hill coefficient of 1.5 +/- 0.13 (mean +/- S.D., n = 4). Substrate inhibition was noted with retinal concentrations greater than 6 microM. The purified enzyme not only recognized retinal generated by microsomes as substrate, but also recognized retinal bound to CRBP. The rates of retinoic acid synthesis from CRBP-retinal, with a series of increasing apoCRBP concentrations, exceeded the rates that would be supported by the free retinal present. The CRBP-retinal complex exhibited allosteric kinetics (K, 0.13 microM; Hill coefficient, 1.75; averages of duplicates) in the presence of excess apoCRBP (the ratio total CRBP/total retinal at each concentration of retinal was 2). This enzyme is likely to play a significant role in retinoic acid synthesis in vivo, because it participates in the synthesis of retinoic acid from a physiologically occurring form of retinol (holoCRBP), reflects retinoid status, and is distributed in extrahepatic tissues in addition to liver. These results also suggest a novel role for CRBP in retinoid metabolism, facilitating the conversion of retinal into retinoic acid.

Aldehyde Oxidoreductases↗

PubMedDate not supplied

Retinal biopsy techniques for the removal of retinal tissue fragments.

Because retinal tissue normally excised during retinal reattachment repair is usually discarded, safe methods for the removal of retinal tissue from the eye were developed. Two methods are described for the removal of retinal tissue fragments otherwise discarded during vitrectomy for retinal detachment repair: (1) the removal of small oval pieces of retinal tissue associated with horseshoe retinal tears and (2) the removal of larger rectangular pieces of retinal tissue associated with relaxing retinotomies or giant retinal tears. These methods provide the retinal surgeon with some simple and safe methods for the extraction of retinal tissue fragments that would otherwise be discarded at the end of surgery.

Biopsy↗

PubMed1997

Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial: 5. Clinical features of cytomegalovirus retinitis at diagnosis. Studies of ocular complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group.

PURPOSE: To examine associations of systemic and ocular characteristics with severity of cytomegalovirus (CMV) retinitis at time of diagnosis and to compare ocular characteristics of eyes with and without CMV retinitis. METHODS: Eleven clinical centers, a data coordinating center, and a fundus photograph reading center participated in a randomized, controlled, multicenter clinical trial comparing foscarnet and ganciclovir as primary therapy for previously untreated CMV retinitis in 240 patients with AIDS. RESULTS: The systemic characteristics marginally associated with the percentage of retina affected by CMV in a patient's worse eye at diagnosis were chronic fever, weight loss, and number of HIV-related illnesses. A positive CMV blood culture at diagnosis was similarly associated with bilateral disease. Laboratory measures of disease did not correlate well with measures of CMV retinitis severity. Many eyes with CMV retinitis had no or minimal lesion hemorrhage, but most had signs of inflammation. Patients often reported visual symptoms for involved eyes. The worse eyes (the eye with lesions covering the most retinal area) of patients with bilateral disease had greater retinal involvement, more lesions, and fewer degrees of visual field than did involved eyes of patients with unilateral disease. Visual symptoms, inflammation, indolent retinitis, and hemorrhagic lesions were associated with a greater percentage of retina affected by CMV. CONCLUSIONS: The findings support viremia as a mechanism of spread for untreated disease. Visual symptoms and signs of ocular inflammation were indicators both of the presence of CMV retinitis and of greater extent of retinal area covered by CMV retinitis lesions.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Prophylactic argon laser coagulation for rhegmatogenous retinal detachment in AIDS patients with cytomegalovirus retinitis.

BACKGROUND: The incidence of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) reaches 20-45%. Despite aggressive medical treatment, rhegmatogenous retinal detachments develop in up to 30% of the affected eyes. Surgical repair is often difficult due to multiple large and hardly visible retinal holes with vitreal traction. Pars plana vitrectomy with instillation of silicone oil is the procedure of choice, giving limited functional results with anatomical reattachment. METHODS: We performed prophylactic laser coagulation in AIDS patients with medically treated CMV retinitis to prevent a progressive retinal detachment. Twenty-two quiescent CMV lesions in 22 eyes of 20 patients were treated with argon green laser coagulation. Each CMV lesion was completely surrounded with a double or triple row of laser spots (500-600 mumols; 0.2 s; gray-white lesions). RESULTS: The duration of follow-up was 2-24 months. Histopathologic evaluation was possible in two eyes of one patient. Reactivated or smoldering CMV retinitis crossed the laser scars in 11 eyes, making additional laser coagulation necessary. In four eyes retinal holes in the CMV scar tissue led to retinal detachment, which stopped at the laser scar. In three eyes the detachment is still controlled by the laser scar. In one eye, the detachment stopped at the laser scar for 6.5 months and then slowly progressed across it. There were no complications associated with our laser treatment. CONCLUSION: Prophylactic argon laser coagulation in quiescent CMV retinitis seems to reduce the rate of progressive retinal detachment with no need for vitrectomy and silicone oil tamponade.

AIDS-Related Opportunistic Infections↗

PubMed2002

Frequency of ciliary body or retinal breaks and retinal detachment in eyes with atopic cataract.

AIM: To determine the frequency of ciliary body or retinal breaks and retinal detachment in eyes with atopic cataract. METHODS: The records of 106 eyes (74 patients) with atopic cataract that underwent cataract extraction were reviewed. The frequency of ciliary body or retinal breaks and retinal detachment was classified by their presence preoperatively and postoperatively, and by cataract type. RESULTS: Breaks were detected preoperatively in 27 eyes (25.5%) of 17 patients in the ciliary body (20 eyes, 18.9%), near the ora serrata (five eyes, 4.7%), and in undefined locations (two eyes, 1.9%). Among these, 16 eyes (15.1%) had already developed retinal detachment. After surgery, a ciliary body break occurred in one eye (0.9%) and retinal detachment in four eyes (3.8%) of three patients. The breaks that caused postoperative retinal detachment were in the ciliary body. When classified by cataract type, the highest frequency of breaks was associated with mature cataracts (35.0%), and all eyes with breaks developed retinal detachment. CONCLUSIONS: One fourth of eyes with atopic cataract had breaks in the ciliary body or ora serrata, or retinal detachment preoperatively. The highest frequency of either breaks or retinal detachment was associated with mature cataract. The frequency of breaks or detachment that occurred postoperatively (approximately 5%) was lower than that present preoperatively.

Adolescent↗

PubMed1992

Role of HIV and CMV in the pathogenesis of retinitis and retinal vasculopathy in AIDS patients.

Cotton-wool spots and cytomegalovirus (CMV) retinitis are seen frequently in AIDS patients. Human immunodeficiency virus (HIV) infection of the retina has been proposed as a mechanism for the high incidence of retinal pathology. An autopsy study of the eyes from 25 consecutive cases of AIDS was performed using gross examination, light microscopy, trypsin digestion of retinal vasculatures, and immunohistochemistry to evaluate the possible role of HIV, as well as CMV, in the pathogenesis of retinitis and retinal vasculopathy. Brain tissue was studied in the first 20 of these cases to evaluate any correlation between retinal and central nervous system pathology. CMV retinitis was observed in 15 cases (60%). Cotton-wool spots were seen in nine cases (36%). CMV encephalitis was detected in four cases, whereas HIV encephalitis was noted in five cases. We were unable to demonstrate a correlation between CMV retinitis and CMV encephalitis. However, the number of cases studied was small, and the frequency of CMV encephalitis was low. On the other hand, bilateral CMV retinitis demonstrated a correlation to HIV encephalitis (P less than 0.005, Fisher's exact test). HIV infection of the retina was not detected by typical morphologic changes or immunohistochemistry. Immunohistochemistry localized CMV infection solely to areas of active retinitis. These findings suggest that bilateral CMV may serve as a marker of HIV encephalitis, possibly indicating a severely immunodepressed state.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1994

Insulin stimulation of retinal outer segment uptake by cultured human retinal pigment epithelial cells determined by a flow cytometric method.

This study investigates the mechanism by which insulin stimulates phagocytosis in cultured human retinal pigment epithelium, using a flow cytometric assay of retinal outer segment uptake. RPE cells were isolated from adult human donors and grown in culture. Retinal outer segments were isolated from fresh bovine eyes and covalently labeled with the fluorescent dye carboxy-SNAFL-2. Retinal outer segment binding and uptake was quantified by direct visualization and the increase in cellular fluorescence measured using a flow cytometer and the methods compared. Uptake measured by flow cytometry was further characterized by concentration, time, temperature and serum stimulation, and shown to be comparable to other published methods. Uptake of retinal outer segments was acutely stimulated by insulin in the absence or presence of serum with half maximal stimulation occurring between 0.1 and 1.0 microgram ml-1. Theophylline, forskolin and cholera toxin all reduced retinal outer segment uptake by RPE cells, but had no effect upon insulin stimulation. Measurements of cAMP showed that insulin did not change intracellular cAMP concentration compared to controls in the absence or presence of added retinal outer segments. One hundred nanomolar okadaic acid also inhibited retinal outer segment uptake but not insulin-stimulated uptake, nor did 100 microM genistein have an effect upon insulin-stimulated uptake. Preincubation of RPE cells with 25 microM ZnCl2 overnight stimulated retinal outer segment uptake and appeared to inhibit the insulin stimulation. Preincubation of the cells in 25 mM glucose overnight also increased the uptake of retinal outer segments over control and reduced the effect of insulin. We conclude that insulin stimulates retinal outer segment phagocytosis by an as yet unknown process which may involve specific tyrosine phosphatases.

Cells, Cultured↗

PubMed1999

Measurement of retinal thickness in normal subjects with retinal thickness analyzer.

The retinal thickness at posterior pole of normal subjects was measured by using retinal thickness analyzer (RTA) to determine the values of retinal thickness and to establish map of retinal thickness in normal subjects. The retina of 6 mm x 6 mm in size (approximately 20 degrees, centered on the macula) at the posterior pole was scanned by using RTA to obtain images of 116 normal eyes of 77 cases of various age group. The images were processed by a computer to obtain the retinal thickness values and the thickness map of this location. The data were analyzed with SAS software package. The mean retinal thickness was 171.77 +/- 26.13 microns with no significant difference among the various age groups (P > 0.05). The thickness maps of the retina of 6 mm x 6 mm size at the posterior pole around the macula rendered a "U"-shaped pattern, extending from the disc to the superior and inferior of the fovea. The retina was found to be thin at temporal side of the fovea, with the thinnest area being at the macula central fovea. The U-shaped pattern of the retinal thickness maps was well in agreement with the topography of the ganglion cells and the retinal nerve fibers in human retina. The measurement of the retinal thickness by RTA reflected the changes in the layers of ganglion cells and the retinal nerve fiber. Each scanning session of RTA examination can yield multiple optical cross-section images of the retina and obtain retinal thickness maps of posterior pole of living eyes.

Humans↗

PubMed2006

Intracellular calcium response and adhesiveness of chick embryonic retinal neurons to photoelectric dye-coupled polyethylene films as prototypes of retinal prostheses.

Photoelectric dyes, which absorb light and convert photon energy to electric potentials, were shown to stimulate retinal neurons in culture. One of these dyes coupled with polyethylene film surface, as a prototype of retinal prostheses, could induce intracellular calcium elevation in chick embryonic retinal tissues. In this study, we used retinal cells from chick embryos in which no photoreceptor outer segments yet developed, and assessed cell adhesiveness and response to the original and modified types of our retinal prostheses. Extruded-blown film of high density polyethylene was used as the original polyethylene film. Polyethylene film surface was modified either by coupling with type 1 collagen or by crystallization from the melt of the original polyethylene film. A photoelectric dye, 2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to these different types of polyethylene films through amide linkage. Retinal cells from chick embryos at the 12-day embryonic stage were cultured on the surface of dye-coupled films. The response of retinal cells to the dye-coupled films was observed by calcium imaging. Cell types, either neurons or glial cells, were detected by immunocytochemical staining and also observed by scanning electron microscopy (SEM). Intracellular calcium elevation was observed in cells, including both neurons and glial cells, on the surface of the original dye-coupled film, collagen-coated dye-coupled film, and dye-coupled recrystallized film, in contrast with no response of cells cultured on the dye-uncoupled plain film. Retinal neurons grew upon colonies of glial cells settling on the surface of all different types of the films. The number of retinal neurons on the collagen-coated dye-coupled film and dye-coupled recrystallized film was significantly larger than the number of neurons on the dye-uncoupled plain film (P = 0.0004, analysis of variance; P < 0.05, Tukey-Kramer test). With SEM, Muller cell-like large cells covered the original dye-coupled film and collagen-coated dye-coupled film, while neuron-like small cells settled directly on the dye-coupled recrystallized film and also formed large colonies on Muller-like cells. Retinal neurons and glial cells were cultured directly on the different types of dye-coupled polyethylene films. Photoelectric dye-coupled polyethylene films could be used as prototypes of retinal prostheses.

Aniline Compounds↗

PubMed2004

Three-year follow-up study of blood-retinal barrier and retinal thickness alterations in patients with type 2 diabetes mellitus and mild nonproliferative diabetic retinopathy.

OBJECTIVE: To examine the 3-year alterations of the blood-retinal barrier and changes in retinal thickness occurring in the macular region in 14 eyes of 14 patients with type 2 diabetes mellitus (DM) and mild nonproliferative diabetic retinopathy. METHODS: We classified 14 eyes of 14 patients with type 2 DM and mild nonproliferative diabetic retinopathy, as having disease levels 20 (microaneurysms only) or 35 (microaneurysm plus retinal hemorrhage[s] and/or hard exudates) of Wisconsin Card-Sorting Test grading, by using 7-field stereoscopic fundus photographs. We examined them 7 times at 6-month intervals, using fundus photography, fluorescein sodium angiography, the retinal leakage analyzer (RLA)-modified confocal scanning laser ophthalmoscope, and the retinal thickness analyzer. The retinal leakage and retinal thickness maps were aligned and integrated into 1 image. Data from the group of individuals with type 2 DM were compared with those of a healthy control population (n = 14; mean age, 48 years; age range, 42-55 years) to establish reference maps for the RLA and retinal thickness analyzers. RESULTS: Areas of abnormally increased fluorescein leakage were detected in all eyes examined at baseline. The sites of increased fluorescein leakage reached values as high as 483% above normal levels, but in 20 of the total 95 examinations performed, fluorescein leakage returned to normal levels. Every eye that showed reversal to normal levels of fluorescein leakage showed stabilization or a decrease in glycosylated hemoglobin A(1c) values at the same visit. When comparing the RLA-leaking sites among the 7 examinations, they remained, in general, in the same locations, but there was a clear fluctuation in the percentage of increases. No clear correlation was observed among the location of areas of increased retinal thickness and RLA-leaking sites, the number of microaneurysms, or the glycosylated hemoglobin A(1c) values. Microaneurysms on fundus photographs showed different cumulative incidences throughout the follow-up period in the different eyes. Associations between these different abnormalities suggest specific patterns of evolution of type 2 DM-related retinal disease. CONCLUSIONS: The dominant alteration in the retina of patients with type 2 DM and mild nonproliferative retinopathy is the presence of RLA-leaking sites. This damage seems to be reversible and directly associated with variations in glycemic metabolic control. Together with the intensity and persistence of RLA-leaking sites, the rates of microaneurysm accumulation and alterations of the foveal avascular zone may characterize different genetically based phenotypes of diabetic retinopathy.

Adult↗

PubMed1985

Rhegmatogenous retinal detachment in Labrador retrievers. I. Development of retinal tears and detachment.

We used clinical and pathologic methods to examine ten Labrador retrievers with ocular and skeletal abnormalities. The major ocular findings were axial myopia; cataract; vitreous abnormalities, including liquefaction, detachment, and vitreoretinal traction; retinal tears; rhegmatogenous retinal detachment; and proliferative vitreoretinopathy. The appendicular skeleton showed retarded bone growth, bone dysplasia, and degenerative arthropathy. Vitreoretinal traction appeared to be the cause of the retinal tears because (1) formed vitreous was always attached near the anterior edge of the tear, and (2) vitreous traction caused a retinal ridge adjacent to a retinal tear in a dog that had not yet developed retinal detachment. The pathogenetic sequence of spontaneous vitreous abnormalities, retinal tears, and retinal detachment observed in these dogs has not previously been described in animals, to the best of our knowledge, and mimicked human rhegmatogenous retinal detachment, particularly those associated with giant retinal tears.

Animals↗

PubMed1995

Silicone oil in repair of retinal detachments caused by necrotizing retinitis in HIV infection.

OBJECTIVE: To evaluate the safety and efficacy of 1000- and 5000-centistoke silicone oil as retinal tamponades for the treatment of retinal detachments secondary to necrotizing retinitis in patients with human immunodeficiency virus (HIV) infection. DESIGN: A prospective observational study. SETTING: Community and university-based ophthalmology clinics. PATIENTS: Three hundred fifty patients with HIV infection, who had 407 eyes with retinal detachments secondary to necrotizing retinitis. INTERVENTION: Vitrectomy surgery for retinal detachment with 1000- or 5000-centistoke silicone oil as the retinal tamponade. OUTCOME MEASURES: Efficacy was measured both by anatomic success (defined as complete retinal attachment or macular attachment) and by visual acuity success (defined as preservation of visual acuity or ambulatory vision). Safety was determined by the rate of complications, including abnormal intraocular pressure and corneal and lens opacification. RESULTS: At the last follow-up examination, the retina was completely attached in 287 (73%) of 393 eyes, the macula was attached in 370 eyes (94%), 268 eyes (68%) had ambulatory vision, and visual acuity was preserved in 219 (56%) of 388 eyes. Corneal opacification, hypotony, and silicone oil emulsification were present in 4%, 2%, and 1% of eyes, respectively. One eye had elevated intraocular pressure. Of the 57 patients who had both eyes treated, 35 died, of whom four (11%) had nonambulatory vision in both eyes. Of the 293 patients who had one eye treated, 122 died, of whom 44 (36%) died with nonambulatory vision in the treated eye. The median time to cataract was 192 days; to nonambulatory vision, 474 days; and to death, 204 days. CONCLUSIONS: Silicone oil repair of retinal detachments in necrotizing retinitis is an efficacious and safe procedure that delays or prevents loss of vision in advanced HIV disease.

Adult↗

PubMed2006

Implication of the hypoxia response element of the Vegf promoter in mouse models of retinal and choroidal neovascularization, but not retinal vascular development.

Retinal neovascularization (NV) and macular edema, resulting from blood-retinal barrier (BRB) breakdown, are major causes of visual loss in ischemic retinopathies. Choroidal NV (CNV) occurs in diseases of the retinal pigmented epithelium/Bruch's membrane complex and is another extremely prevalent cause of visual loss. We used mice in which the hypoxia response element (HRE) is deleted from the vascular endothelial growth factor (vegf) promoter (Vegf(delta/delta) mice) to explore the role of induction of VEGF through the HRE in these disease processes. Compared to wild type (Vegf+/+) mice with oxygen-induced ischemic retinopathy (OIR) in which vegf mRNA levels were increased and prominent retinal NV and BRB breakdown occurred, Vegf(delta/delta) littermates with OIR failed to increase vegf mRNA levels in the retina and had significantly less retinal NV and BRB breakdown, but showed prominent dilation of some superficial retinal vessels. Vegf(+/delta) littermates with ischemic retinopathy developed comparable retinal NV to Vegf+/+ mice, exhibited intermediate levels of BRB breakdown, and did not show vasodilation. In a mouse model of CNV, due to laser-induced rupture of Bruch's membrane, the area of CNV at Bruch's membrane rupture sites was more than tenfold greater in Vegf+/+ mice than in Vegf(delta/delta) littermates. In contrast to these dramatic differences in pathologic ocular NV, Vegf(delta/delta) mice showed subtle differences in retinal vascular development compared to Vegf+/+ mice; it was slightly delayed, but otherwise normal. These data suggest that induction of VEGF through the HRE in its promoter is critical for retinal and CNV, but not for retinal vascular development.

Animals↗