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P. Fournie, F. Cabon, D. Compagno, J. Coullet, F. Malecaze; SiRNA Targeting Vascular Endothelial Growth Factor : Inhibition of an FGF–induced Corneal Angiogenesis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1647.
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To determine whether small interference RNA (siRNA) targeting VEGF, delivered subconjunctivally or intrastromally, could be used to suppress the FGF–induced corneal angiogenesis involved in the pathogenesis of several corneal neovascularization diseases.
Uniformly sized hydron pellets containing Fibroblast Growth Factor were prepared and implanted into the corneal stroma of New Zealand albino rabbits at 2 mm from the limbus. Anti–VEGF A siRNA was locally delivered by subconjunctival injection or corneal intrastromal injection between the limbus and the pellet at 1 and 3 days after pellet implantation. Angiogenesis was evaluated at days 3 and 7 after pellet implantation by using calipers with a stereomicroscope. Quantitative RT–PCR was performed on total cellular RNA isolated from corneas at day 7.
Early onset and profound neovascularization was observed in control eyes. Significant inhibition of corneal neovascularization was observed in both groups treated with siRNA versus controls (p < 0.05) even if intrastromally injected rabbits showed a significant lower response (p < 0.05) than those subconjunctivally injected. Preliminary results of quantitative RT–PCR seem to be closely correlated with clinical observations.
These results suggest that the use of anti–VEGF siRNA with two different delivery systems could represent a usefull therapy against neovascularization–related corneal diseases.
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