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At least 649 records · Page 36Linked to original sources

Corneal electroretinographic function rescued by normal retinal pigment epithelial grafts in retinal degenerative Royal College of Surgeons rats.

PURPOSE: This study was designed to examine whether retinal function can be rescued by allogeneic normal retinal pigment epithelial (RPE) grafts in Royal College of Surgeons (RCS) with retinal degeneration and, if so, whether this rescued function can be measured and followed by recording the corneal electroretinogram (ERG). METHODS: RPE donors were RCS-Long Evans crossbred F1 rats with phenotypically normal retinas. Half an RPE sheet was implanted in the subretinal space of RCS rats at postnatal day 20. The fundi of the recipients' eyes were examined, and the corneal ERGs were recorded. The eyes were also examined histologically. RESULTS: The RPE grafts were identified by fundus examination in all 21 recipients. No clinical or histologic evidence of inflammation was detected in the media or the retina of the host eye. Eighteen of 21 (86%) recipients showed rescued corneal ERG function. In nine recipients, the PIII response in the grafted eye was significantly greater than in the nongrafted eye. In the other nine recipients, the ERG in the grafted eye showed a b-wave and an a-wave, whereas no b-wave was detected in the nongrafted eye. Recipients of the sham operation (n = 13) revealed no ERG function rescue. To determine long-term corneal ERG function in RPE recipients, 8 of 18 animals in which ERG function was rescued were randomly selected for continued observation. These recipients sustained rescued ERG function for 16 to 17 weeks, at which time the experiment ended. CONCLUSION: Results indicate that retinal function of degenerative RCS rats, as measured by corneal ERG, can be rescued by implantation of allogeneic normal RPE into the subretinal space of the eye. Furthermore, this rescued function can be followed up over a relatively long period of time, thus providing a useful model for studying the functional changes of RPE allografts resulting from either immunologic or neurobiologic influences.

Animals↗

Tumor necrosis factor and nitric oxide production by retinal Müller glial cells from rats exhibiting inherited retinal dystrophy.

The primary cause of the inherited retinal dystrophy observed in Royal College of Surgeons (RCS) rats is located in the retinal pigmented epithelium, which is unable to phagocytize photoreceptor outer segments. We have demonstrated here that retinal Müller glial (RMG) cells obtained from RCS dystrophic rats and stimulated in vitro with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) accumulated higher levels of tumor necrosis factor (TNF) and inducible nitric oxide synthase (NOS II) mRNA and released in culture supernatants significantly higher amounts of TNF and nitrite compared to cells derived from nondystrophic controls. The TNF and NOS II mRNA expression and TNF and nitrite synthesis induced in RMG cells from both strains by LPS + IFN-gamma was significantly prevented by including transforming growth factor-beta (TGF-beta) in the culture medium. Coincubation of the stimulants with an inhibitor of NOS II, NG-monomethyl-L-arginine (L-NMMA), while inhibiting nitrite synthesis, induced an increase of TNF production in supernatants from RMG cells without increasing TNF mRNA levels. The retinal dystrophy observed in RCS dystrophic rats could result from an abnormal susceptibility of RMG cells form RCS dystrophic rats to produce TNF and NO in response to stimulants. Administration of the immunomodulatory cytokine TGF-beta or inhibitors of NOS II would provide additional research avenues for photoreceptor rescue.

Animals↗

Axonal injury alters alternative splicing of the retinal NR1 receptor: the preferential expression of the NR1b isoforms is crucial for retinal ganglion cell survival.

Cellular-specific splicing of the retinal NMDAR1 receptor (NR1) and expression of NMDAR2 receptor (NR2) subunits in response to optic nerve injury was investigated by in situ hybridization in adult rats. A controlled optic nerve crush led to a clear alteration in the expression of alternatively spliced NR1 variants in the retinal ganglion cell layer (GCL). The NR1-2b and NR1-4b isoforms were preferentially expressed between 2 d and 1 week after injury, whereas expression for all other isoforms remained either unchanged or decreased to barely detectable levels within 4 weeks. Cellular silver grain density for NR2 subunits also declined in the GCL after trauma. To directly test the hypothesis that NR1b expression is crucial for cell survival after axonal trauma, we administered intraocularly an antisense oligonucleotide against the NR1b isoform 2 and 3 d after injury. This led to a drastic loss of retrogradely labeled retinal ganglion cells (RGCs). Antisense targeting clearly reduced retinal NR1 protein levels, as judged by Western blot analysis, but had no effect on the cell number in control retinas. These findings point toward injury-specific changes in alternative splicing of the NR1 receptor, which are crucial for the survival of RGCs after partial axonal trauma. We therefore propose that this reflects an adaptive, rather than a pathogenic, cellular response to neurotrauma.

Alternative Splicing↗

Vitrectomy for macular pucker. Use after treatment of retinal tears or retinal detachment.

We review our experience and present an analysis of 119 consecutive cases of macular pucker treated by vitrectomy and removal of the epiretinal tissue following treatment for acute retinal tears (16 eyes) or rhegmatogenous retinal detachment (103 eyes). Vision improved postoperatively in 104 (87%) of the 119 eyes. Final visual acuity of 20/60 or better was achieved in 38 (75%) of 51 cases in which the macula had not been detached previously and in 12 (24%) of 52 cases with prior macular detachment. Two preoperative factors were associated with a final visual acuity of 20/100 or better: (1) macula not involved by the original retinal detachment, and (2) thin epiretinal membrane.

Adolescent↗

Cataract extraction after silicone oil repair of retinal detachments due to necrotizing retinitis.

Cataract is common after silicone oil repair of retinal detachment due to necrotizing retinitis in acquired immunodeficiency syndrome. Surgical management has not been reported. Twenty-two eyes of 19 patients were reviewed. The majority underwent phacoemulsification with a posterior chamber convexoplano implant without iridotomy Complications included capsular fibrosis and hyphema. Unpredictable refractions in the first 16 eyes prompted refinement of lens calculations and resulted in a reduction in refractive errors. A 3-step modification of intraocular lens calculations is recommended: (1) use of specific sound velocities to calculate axial length; (2) use of convexoplano lenses; and (3) addition of a constant to the lens power to compensate for the refractive index of silicone oil. Good surgical technique and accurate lens calculations should improve management of cataracts that arise after retinal detachment repair with silicone oil in patients with acquired immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗

Retinitis pigmentosa and a retinal vasculopathy of the Coats type.

Retinitis pigmentosa is occasionally associated with a vasculopathy of the Coats type. Although the clinical appearance of the vaculopathy is similar to that seen in the usual patient iwth Coats's disease, cases associated with retinitis pigmentosa are usually bilateral, equally common in females, and are not seen in childhood. These findings suggest a different etiological process. We speculate that the etiology in such cases may be related to the vascular narrowing and slower circulation known to occur in some retinitis pigmentosa patients.

Adult↗

Extensive dynamics in location, shape, and size of aneurysms in a patient with idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. Idiopathic retinal vasculitis, aneurysms, and neuroretinitis.

PURPOSE: To describe an unusual case of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome with rapid dynamics in the number and appearance of the aneurysms. DESIGN: Observational case report. METHODS: Clinical and angiographic data of the patient were reviewed. RESULTS: In the course of only 6 months, preexisting retinal aneurysms resolved while new ones appeared. Changes were observed in the shape and size of preexisting lesions. The resolution of lesions in eyes previously untreated by laser is reported for the first time. CONCLUSIONS: Vascular lesions in IRVAN syndrome may show an unusually rapid turnover. The resolution of aneurysms is a part of the natural course of the disease and may occur without previous retinal laser photocoagulation.

Adult↗

Combined central retinal vein occlusion and cilioretinal artery occlusion associated with prolonged retinal arterial filling.

We examined four healthy men who developed cilioretinal artery occlusion associated with central retinal vein occlusion. Unlike previously reported patients with this clinical entity, there appeared to be abnormal central retinal artery inflow, as evidenced by prolonged, irregular filling of the branch retinal arteries with intravenous fluorescein angiography. The patients were treated with systemic corticosteroids. All of the patients had initial improvement in vision. However, three of the four patients had recurrent episodes of visual loss. The final visual acuity was 20/40 or better in three of the four patients.

Adult↗

Retinal detachment following the acute retinal necrosis syndrome.

Twenty-six patients with the acute retinal necrosis involving 32 eyes have been followed at the Bascom Palmer Eye Institute. Sixteen eyes developed retinal detachment and surgical repair was attempted in thirteen. Ten eyes were successfully reattached. Vitreous surgery was necessary in ten eyes and was performed in eight of the ten successful eyes. The clinical characteristics of the retinal detachments as well as the surgical procedures and results are presented.

Acute Disease↗

Retinal pigment epithelial folds associated with retinal pigment epithelial detachment in macular degeneration.

The authors reviewed six eyes that had a shallow retinal pigment epithelial detachment with the retinal pigment epithelium (RPE) thrown into folds. A contraction of subpigment epithelial fibrovascular tissue causes a folding of the overlying, intimately adherent RPE. Retinal pigment epithelial folds are a sign of subretinal neovascularization and are another manifestation of age-related macular degeneration.

Aged↗

[Risk factors for retinal redetachment by proliferative vitreoretinopathy after episcleral surgery for pseudophakic retinal detachment].

BACKGROUND: Conventional buckling procedures in pseudophakic eyes are more often than in phakic eyes complicated by proliferative vitreoretinopathy (PVR). PATIENTS: The records of 68 patients (68 eyes) suffering from pseudophakic retina detachment between January 1988 to March 1993 were evaluated. We analysed the frequency of PVR-redetachment and possible risk-factors. RESULTS: Thirteen eyes (19%) developed PVR-redetachment after external surgery. Within this group we were not able to find a retinal break before or during surgery in 70% of patients (9 eyes), compared to 25% of patients in the group without PVR complication. CONCLUSIONS: Uncertain visualisation of the retinal break prior to and during external surgery along with persistent retinal detachment represent risk factors for PVR. Also, extended indentation and cryotherapy during frustrane hole localisation is likely to reduce absorption of subretinal fluid and increase blood-ocular-breakdown. Both factors are known to raise the risk of PVR. Whether or not these severe disadvantages of "blind buckling" can be relieved by primary vitrectomy is subject of future investigations.

Adult↗

[Moschcowitz syndrome and retinal neovascularization with retinal detachment].

The authors examined a patient with thrombotic thrombocytopenic purpura (Moschcowitz's disease). Six months after the patient was first seen with massive bilateral vascular occlusion, she presented with advanced retinal neovascularization in both eyes and traction retinal detachment in the left eye. While traction retinal detachment is a very rare sequela of this hematologic disorder, patients with Moschocowitz's disease should be carefully examined for early signs of ocular neovascularization in order to prevent loss of residual vision.

Adult↗

[Retinal hemorrhage associated with retinal artery macroaneurysm (author's transl)].

A report on four cases of an isolated aneurysm of a major retinal artery branch accompanied by retinal hemorrhage and edema (so-called macroaneurysm of the retinal arteries (Robertson)]. In two cases an indirect argon laser coagulation was performed, which facilitated absorption of the associated macular edema and rapidly improved visual acuity.

Adult↗

Retinal dystrophies associated with peripheral retinal vasculopathy.

A pair of identical twins with cone-rod dystrophy and 1 patient with dominant retinitis pigmentosa are reported who had a peculiar vascular retinopathy characterised by perivenous accumulation of fluorescein in the temporal periphery. Other retinal dystrophies associated with leaking retinal vessels are discussed.

Adult↗

Knock-down of GFRalpha4 expression by RNA interference affects the development of retinal cell types in three-dimensional histiotypic retinal spheres.

PURPOSE: To determine the role of glial cell line-derived neurotropic factor family receptor alpha 4 (GFRalpha4) during retinogenesis in a three-dimensional histiotypic in vitro model of the embryonic chicken retina. METHODS: Retinal spheres were cultured from dissociated 6-day-old chicken retina under permanent rotation and transfected with GFRalpha4 siRNA at culture day 2. Alterations on proliferation, apoptosis, and differentiation were determined by semiquantitative RT-PCR, in situ hybridization, and immunohistochemistry after 24, 48, and 72 hours. RESULTS: In contrast to control cultures, retinal spheres transfected with GFRalpha4 siRNA showed reduced GFRalpha4 mRNA expression of only 38% after 24 hours, 3% after 48 hours, and 5% after 72 hours. Based on the suppression of GFRalpha4, a decline in proliferating cells from 10% to 4.8% even after 24 hours and a reduction of sphere size by up to 25% at later culture stages were observed. Moreover, the number of Pax 6-positive amacrine, ganglion, and horizontal cells was significantly decreased from 36% to 16% in GFRalpha4 siRNA-transfected retinal spheres 72 hours after transfection. Additionally, GFRalpha4 gene silencing affected the development of different types of photoreceptors, as revealed by a significant decrease of blue opsin mRNA expression from 29% to 2%, whereas green opsin mRNA and the number rho4D2-positive photoreceptors were significantly increased. CONCLUSIONS: These data showed for the first time that GFRalpha4 plays an essential role in regulating, at least in vitro, the development and differentiation of various cell types during retinogenesis.

Amacrine Cells↗

EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown.

The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy. In the study described herein, we demonstrated that EphA2 stimulation by ephrinA1 in cultured bovine retinal endothelial cells inhibits VEGF-induced VEGFR2 receptor phosphorylation and its downstream signaling cascades, including PKC (protein kinase C)-ERK (extracellular signal-regulated kinase) 1/2 and Akt. This inhibition resulted in the reduction of VEGF-induced angiogenic cell activity, including migration, tube formation, and cellular proliferation. These inhibitory effects were further confirmed in animal models. Intraocular injection of ephrinA1 suppressed ischemic retinal neovascularization in a dose-dependent manner in a mouse model. At a dose of 125 ng/eye, the inhibition was 36.0 +/- 14.9% (P < 0.001). EphrinA1 also inhibited VEGF-induced retinal vascular permeability in a rat model by 46.0 +/- 10.0% (P < 0.05). These findings suggest a novel therapeutic potential for EphA2/ephrinA1 in the treatment of neovascularization and vasopermeability abnormalities in diabetic retinopathy.

Animals↗

[Retinal blood flow changes in eyes with rhegmatogenous retinal detachment and scleral buckling procedures].

Bidirectional laser Doppler technique and monochromatic photography was used to measure the absolute blood flow rate (F) in the major superior or inferior temporal retinal arteries in 3 patients with rhegmatogenous retinal detachment, in 4 patients following unilateral scleral buckling procedures, and in one patient before and after removal of scleral buckling elements. In 2 of the eyes with retinal detachment, F in arteries supplying the detached portion of the retina was approximately 30% lower than in arteries supplying the attached portion. On average, F measured in the arteries supplying the detached portion of the retina in 2 patients was 8.9 +/- 1.3 microliters/min, 67% lower than normal controls. F measured in the arteries supplying the attached portion of the retina in 3 patients was 15.2 +/- 3.9 microliters/min, on average, 43% lower than in normal controls. In 4 patients who had undergone uncomplicated, unilateral scleral buckling procedures, F in an artery of the affected eye was compared with F in the corresponding artery of the fellow eye. F in the artery of the affected eyes was 8.7 +/- 3.2 microliters/min, on average, 59% lower than that of the fellow eyes (p less than 0.05), and 68% lower than in normal controls (p less than 0.0001). Removal of scleral buckling elements in one patient produced a 79% increase in F in the measured artery. Then, F returned to normal levels after removal of scleral buckling elements.

Adult↗