VEGF-TRAPR1R2 Suppresses Choroidal Neovascularization(CNV) and VEGF-Induced Breakdown of the Blood-Retinal Barrier(BRB)

Abstract

Abstract: : Purpose: VEGF-TRAP_R1R2 is a fusion protein that combines ligand binding elements taken from the extracellular domains of VEGF receptors 1 and 2 fused to the Fc portion of IgG1. It is a specific inhibitor of VEGF. The purpose of this study was to investigate the effect of VEGF-TRAP_R1R2 in models of CNV, subretinal NV, and breakdown of the BRB. Methods: : The effect of subcutaneous injections of VEGF-TRAP_R1R2 was tested in mice with laser-induced rupture of Bruch's membrane, transgenic mice that express VEGF in photoreceptors, and in two models of VEGF-induced breakdown of the BRB. Results: Subcutaneous injections or a single intravitreous injection of VEGF-TRAP_R1R2 strongly suppressed CNV in mice with laser-induced rupture of Bruch's membrane. Subcutaneous injections of VEGF-TRAP_R1R2 also significantly inhibited subretinal NV in rhodopsin/VEGF transgenic mice, and significantly reduced BRB breakdown in mice in which recombinant VEGF was injected into the vitreous cavity and in double transgenic mice with doxycycline-induced expression of VEGF in the retina. Conclusions: These data confirm that VEGF is a critical stimulus for the development of CNV and indicate that VEGF-TRAP_R1R2 may provide a new agent for treatment of patients with CNV and diabetic macular edema.

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