Inhibitory Effect of Antibody to alphavbeta5 in Corneal Angiogenesis

ABSTRACT

PURPOSE: This study investigated the importance of alphavbeta5 function during vascular endothelial growth factor (VEGF) induced corneal angiogenesis by examining the effects of antibody to alphavbeta5 that blocks alphav 5-mediated cell adhesion to vitronectin. METHODS: A hydrogel disk containing 500 ng of VEGF was implanted into the superior corneal stroma of each of sixteen New Zealand white rabbit eyes. Each eye also received a second hydrogel disk placed adjacent to the first, randomized to contain either 40 g of antibody to alphavbeta5 (n=8) or phosphate-buffered saline (PBS)(n=8). Both disks were positioned 1.2 mm apart from the superior limbus. Eyes were examined daily under a stereomicroscope by two observers and assigned an angiogenesis score based on number and length of new blood vessels. RESULTS: On days 3 through 7 postimplantation, angiogenesis scores were significantly lower in eyes treated with antibody to alphavbeta5 (averaged score=16.33) as compared to eyes treated with PBS (averaged score=26.52)(P<0.05, Wilcoxon signed rank test). CONCLUSIONS: In a rabbit corneal micropocket assay, antibody to alphavbeta5 inhibits corneal angiogenesis induced by VEGF. Substances that target the integrin alphavbeta5 subunit may have therapeutic potential in disorders characterized by ocular neovascularization.