Inhibition of Corneal Angiogenesis by Orally Administered Thalidomide

ABSTRACT

Thalidomide, a potent teratogen, is Known as an angiogenic inhibitor. This study was performed to examine the effect of thalidomide on corneal angiogenesis in rabbit cornea induced by chemical cauterization. We applied Whatman filter paper disc soaked in 30% silver nitrate (AgNO3) application on corneas of 12 white rabbits. After 5days, we administered oral dose of 100mm2 thalidomide to the 6 animals everyday and examined the length and extent of neovascularization to evaluate the area of neovascularization. After 2 days of oral administration, the increase of neovascularization is 14.3+/-11.7mm2in thalidomide-treated group and 27.9+/-14.6mm2 in cotrol grop. The area of neovascularization reached to its maximum at day 9 in thalidomide-treated group compared to day 11 in control group and decreased thereafter in both groups. The increase of the area of vascularized cornea revealed 28.0+/-13.5mm2 in thalidomide-treated group and 44.4+/-12.7mm2 in control group at the day 9 (p=0.04, Wilkoxon Matched-pairs signed-rank test). This fact means that treatment with thalidomide resulted in an inhibition of the area of vascularized cornea with the median inhibition of 37.3%. On light micrographs, there were infiltration of inflammatory cell and capillary lumens in corneal stroma in both animals. Electron micrographs of thalidomide-treated animals showed loss of vascular endothelial cell junction, mitochondrial swelling and loss of cristae which were not found in control animals. This results suggest that orally-administered thalidomide has a direct effect on the growing vasculature and an inhibitory effect on corneal angiogenesis.