Inhibition of Vascular Endothelial Growth Factor Induced Corneal Angiogenesis by Antibody to Intergrin beta3 Subunit

ABSTRACT

Vascular cells respond to multiple cytokines, they also express a variety of integrin adhesion receptor. A number of the vascular cell integrins are functionally and structurally homologous, suggesting some level of biologic redundancy. We investigated the importance of alphavbeta3 function during vascular endothelial growth factor(VEGF) induced corneal angiogenesis by examining the effects of 9D491, a monoclonal antibody against beta3 that blocks alphavbeta3-mediated cell adhesion to vitronectin and fibrinogen. A hydrogel disk containing 500ng of VEGF was implanted into the superior corneal stroma of each of twelve New Zealand white rabbit eyes. Each eye also received a second hydrogel disk placed adjacent of the first, randomized to contain either 2.6microgram of 9D491 mAb(n=6) or 6E10, an irrelevant antibody of the same isotype, (n=6). Both disks were positioned 1.2mm from the superior limbus. Eyes were examined daily under a streomicroscope by two masked observers and assigned an angiogenesis score based on number and length of new blood vessels. On days 5 through 7 postimplantation, angiogenesis scores were not significantly lower in eyes treated with anti-alphavbeta3 mAb (averaged score=21.6) as compared to eyes treated with 6E10 (averaged score=24.0) (p<0.2, Wilcoxon rank sum test). In a rabbit corneal pocket assay, monoclonal antibody to beta3 could not inhibit corneal angiogenesis induced by VEGF.