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Y. Liu, J. Cao, R.A. Renard, H. Song, D. Hylton, J.S. Rudge, N. Papadopoulos, G.D. Yancopoulos, S.J. Wiegand; Low Dose, Subconjunctival Administration of VEGF Trap Inhibits Suture–Induced Corneal Neovascularization and Inflammation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1626.
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We have previously reported that systemic administration of VEGF Trap markedly inhibited neovascularization in response to corneal injury in rodent models. The present study evaluates the effect of subconjunctival delivery of VEGF Trap at very low doses on the development of neovascularization following corneal suture injury.
Corneal neovascularization (NV) was induced by intrastromal placement of three nylon sutures in adult male Sprague–Dawley rats. VEGF Trap was administered subconjunctivally at four doses (100 mcg, 50 mcg, 25 mcg, or 5 mcg in 50 mcL / eye) immediately after injury (day 0) and on days 3 and 6 post–injury. Control animals received injections of vehicle following the same schedule. The growth of corneal neovessels was evaluated in–life by slit–lamp microscopy. The corneal vasculature was labeled by intravenous injection of FITC conjugated Concavalin A, and the extent of NV was evaluated post–mortem in corneal flat–mounts. The Scion Image program was used to measure the length of corneal neovessels. Infiltration of leukocytes was observed in cross–sections stained with H&E. Serum levels of free VEGF Trap were determined by anti–VEGF Trap ELISA on day 9.
Subconjunctival administration of VEGF Trap significantly inhibited corneal neovascularization at all doses tested, though the extent of inhibition was dose dependent (97% to 82% inhibition). The infiltration of leukocytes also was attenuated. Systemic administration of VEGF Trap at the highest of the above doses (100 mcg on days 0, 3 and 6) did not inhibit corneal NV or infiltration of leukocytes. Unbound VEGF Trap was not detected in the serum following multiple subconjunctival injections.
Subconjunctival administration of low dose of VEGF Trap suppresses the development of corneal neovascularization and reduces the infiltration of leukocytes into the cornea following injury, in the absence of appreciable systemic exposure.
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