A VEGF121–Gelonin Fusion Protein (VEGF121/rGel) Induces Regression of Subretinal and Choroidal Neovascularization (CNV)

Abstract

Abstract: : Purpose: Intravascularly injected VEGF₁₂₁/rGel selectively binds and damages tumor vessels. In this study, the effect of intravascular or intravitreous injection of VEGF₁₂₁/rGel was tested in two models of ocular neovascularization (NV). Methods: One week after rupture of Bruch’s membrane the baseline amount of CNV was measured in a group of mice and remaining mice received injection of VEGF₁₂₁/rGel or rGel and after one week the amount of CNV was measured. A similar protocol was used in rho/VEGF mice. VEGF₁₂₁/rGel was localized in ocular sections by immunohistochemistry. Results: In rho/VEGF mice, intravitreous injections of 0.005 µg VEGF₁₂₁/rGel starting at postnatal day (P) 21 resulted in a significant reduction in total area of subretinal NV per retina at P25 compared with vehicle–injected mice. In mice with established CNV one week after rupture of Bruch’s membrane, tail vein injections of 45 mg/kg of VEGF₁₂₁/rGel every two days for 1 week or a single intravitreous injection of 0.005 µg of VEGF₁₂₁/rGel resulted in significant reductions in CNV area at rupture sites compared with the baseline area before treatment. After intravascular or intravitreous injections, VEGF₁₂₁/rGel was localized to CNV lesions with no staining of normal retinal or choroidal vessels. Conclusions: These data indicate that after either intravascular or intravitreous injections of VEGF₁₂₁/rGel, it localizes to new vessels in the eye and causes regression of the neovascularization. Vascular targeting with VEGF₁₂₁/rGel provides a new approach for inducing regression of ocular NV.

Keywords: drug toxicity/drug effects • choroid: neovascularization • retinal neovascularization