Efficacy of fumagillin bicyclohexylamine on experimental corneal neovascularization in rat model.

Abstract

Fumagillin has been previously used to treat corneal microsporidial keratitis and also identified as an angiogenesis inhibitor. This study aimed to evaluate efficacy of fumagillin bicyclohexylamine on the rat model of corneal neovascularization induced by silver nitrate cauterization. Twenty-four Albino Wistar rats (n = 24) were divided into three groups. Following silver nitrate-induced corneal injury, eyes in Group 1 received one drop of 5mg/mL topical fumagillin bicyclohexylamine four times daily for 10days. Group 2 received subconjunctival injection of 0.1mL fumagillin bicyclohexylamine (2.5mg/mL) on day 1 and day 5. Group 3 received artificial tears and lubricants four times daily for 10days as control. On day 10, animals were sacrificed. Corneal specimens were obtained and prepared to assess vascular endothelial growth factor (VEGF-C) levels and corneal angiogenic microvessel density. There was no significant difference in VEGF-C levels between the groups (P = 0.994). Assessment of angiogenic microvessel density for peripheral corneal zone also did not reveal significant difference between the groups (P = 0.113). However, mean vascular density in Group 1 and Group 2 was significantly higher for both midperipheral and central corneal zones in comparison with Group 3 (P = 0.003, P = 0.015). Previously proved to be effective for treatment of microsporidial keratitis in humans, topical and subconjunctival concentration or dosing of fumagillin bicyclohexylamine failed to reduce corneal neovascularization induced by silver nitrate in this study. Further studies comparing different concentrations and dosing may detect inhibitory effects of fumagillin on corneal neovascularization without inducing toxicity.