FIBROBLAST GROWTH-FACTOR-2, HEPARIN AND SURAMIN REDUCE EPITHELIAL ULCER DEVELOPMENT IN EXPERIMENTAL HSV-1 KERATITIS

Background: We have previously shown that basic fibroblast growth fact or (FGF-2) enhances corneal epithelial healing in different experiment al models in vivo. In order to study the healing effect of this growth factor in pathological conditions of the cornea, we investigated whet her topical application of FGF-2 could affect herpes keratitis in rabb its. Since HSV-1 infection is prevented in vitro by incubation with he parin, we also topically applied heparin and suramin, considering the similar interaction of herpes simplex virus and FGF-2 with cell membra ne-anchored heparan sulfate. Methods: After virus inoculation with a h uman BEY.2 strain, rabbits were treated with either FGF-2 (200 ng to 2 mu g/application), heparin (250 mu g/application) or suramin (250 mu g/application)4 times daily until day 14. Acyclovir and placebo admini strations served as controls (n=48 rabbits). Computerized ulcer surfac e analysis, clinical observations and virus recovery assays were per f ormed. a Results: Topical FGF-2, heparin and suramin treatment reveale d a significant reduction in peak ulcer sizes, and complete epithelial healing was achieved earlier than in placebo-treated corneas. However , no significant antiviral effect of FGF-2, heparin and suramin was de tectable in plaque assays from conjunctival swabs. a Conclusions: Thes e experiments demonstrate that FGF-2 is effective in promoting herpeti c epithelial ulcer healing, either due to its proliferative effects on epithelial cells or indirectly by occupying the sites on cell surface heparan sulfate necessary for the attachment of the virion. The latte r mechanism of action is presumably the reason for the similar effect of heparin and suramin.