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J. L. Dreyfuss, C. V. Regatieri, G. B. Melo, D. Lavinsky, M. E. Farah, H. B. Nader; Dual Role of Intravitreous Infliximab in Experimental Choroidal Neovascularization. Effect on the Expression of Sulfated Glycosaminoglycans. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2968.
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To determine the effects of an anti-TNF- (infliximab) in a laser-induced choroidal neovascularization (CNV) model in rat eyes by fluorescein angiogram, immunofluorescence and glycosaminoglycan analyses.
Induction of CNV was performed using an argon laser. At the end of the laser session, saline or infliximab were injected intravitreously. The animals were divided into 7 groups (control, laser, and laser with 10, 20, 40, 80 or 320 µg of infliximab). After three weeks, fluorescein angiogram was performed using the Heidelberg Retina Angiograph (HRA-2) to measure the area of CNV. The eyes were then enucleated and immunofluorescence was performed (flatmount) with von Willebrand factor for endothelial cells. The cytotoxicity of infliximab was evaluated in cultured retinal pigmented epithelial cells. The expression of sulfated glycosaminoglycans was determined in the retina and choroid in animals metabolically labeled with [35S]-sulfate.
Fluorescein angiogram showed significant reduction in the groups treated with low doses of infliximab (10-40 µg). These findings were confirmed by immunofluorescence which showed 49% decrease in the CNV area compared to control eyes. Heparan sulfate expression in both retina and choroid tissues paralleled the observed effects on angiogenesis. The increases in the expression of chondroitin sulfate in retina and dermatan sulfate in choroid reflect the effects of injury and fibrosis using high doses of the antibody. No cytotoxic effect was detected.
Intravitreal infliximab has a dual effect on the development of laser-induced CNV. At low doses, it reduces angiogenesis and glycosaminoglycan expression, whereas opposite effects are seen at high doses.
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