VEGF Trap R1R2 Suppresses Experimental Corneal Angiogenesis

Abstract

Purpose

To determine the effect of vascular endothelial growth factor (VEGF) Trap_R1R2 on bFGF-induced experimental corneal neovascularization (NV).

Methods

Control pellets or pellets containing 80 ng bFGF were surgically implanted into wild-type C57BL/6 and VEGF-LacZ mouse corneas. The corneas were photographed, harvested, and the percentage of corneal NV was calculated. The harvested corneas were evaluated for VEGF expression. VEGF-LacZ mice received tail vein injections of an endothelial-specific lectin after pellet implantation to determine the temporal and spatial relationship between VEGF expression and corneal NV. Intraperitoneal injections of VEGF Trap_R1R2 or a human IgG Fc domain control protein were administered, and bFGF pellet-induced corneal NV was evaluated.

Results

NV of the corneal stroma began on day 4 and was sustained through day 21 following bFGF pellet implantation. Progression of vascular endothelial cells correlated with increased VEGF-LacZ expression. Western blot analysis showed increased VEGF expression in the corneal NV zone. Following bFGF pellet implantation, the area of corneal NV in untreated controls was 1.05±0.12 mm² and 1.53±0.27 mm² at days 4 and 7, respectively. This was significantly greater than that of mice treated with VEGF Trap (0.24±0.11 mm² and 0.35±0.16 mm² at days 4 and 7, respectively; p<0.05).

Conclusions

Corneal keratocytes express VEGF after bFGF stimulation and bFGF-induced corneal NV is blocked by intraperitoneal VEGF TrapR1R2 administration. Systemic administration of VEGF TrapR1R2 may have potential therapeutic applications in the management of corneal NV.