Inhibition of Corneal Angiogenesis by a Farnesyl Transferase Inhibitor

ABSTRACT

Farnesyl transferase inhibitor(FTI) disrupt farnesylation of ras protein and thus, suppress tumor growth in vivo. The ras oncogene is thought to contribute to tumor development directly by promoting tumor cell proliferation and indirectly by stimulating vascular endothelial growth from Cinnamomum Cassia Blume(CB2`-ph) interferes with angiogenesis, we studied the effect of CB2`-ph on rabbit corneal angiogenesis induced by VEGF. A hygrogel disk containing 250ng of VEGF was implated intrastromally in the superior cornea of 16 NZW rabbit eyes. All eyes received a second intrastromal disk, randomized to contain either 40 micro gram of CB2`-ph(n=8) or phosphate-buffered saline(PBS)(n=8). Both disks were positioned side-by-side, 1.2mm from the superior limbus. Each eye was examined daily by two masked observers and assigned an angiogenesis score based on number and length of new blood vessels. At 3, 5 and 7 days postimplantation of VEGF disks, eyes treated with CB2`=ph showed mean angiogenesis score of 2.0 +/- 1.7, 13.4 +/- 6.6 and 23.8 +/- 11.3, respectively, while PBS=treated controls scored 8.6 +/- 4.4, 30.3 +/- 20.8 and 52.2 +/- 26.9, respectively(p<0.05, Wilcoxon signed rank test). In a rabbit corneal pocket assay, CB2`-ph appears to be effective on VEGF-induced corneal angiogenesusis in the model.