ANTIMETABOLITE INTERACTIONS WITH EPIDERMAL GROWTH-FACTOR

Antimetabolites such as 5-fluorouracil and mitomycin C are known to de lay wound healing. Epidermal growth factor (EGF) has been shown to acc elerate corneal epithelial wound healing. This study was designed to i nvestigate the effects of EGF on corneal epithelial healing that has b een modified by antimetabolite treatment. New Zealand White rabbits we re pretreated with either saline (controls) or 5-fluorouracil (5FU) in jected subconjunctivally, or mitomycin C (MMC) applied topically. Circ ular anterior stromal wounds were created, followed by a 6-hour perfus ion of normal saline or 50 mu g/ml of EGF. Subconjunctival saline or 5 FU, or topical MMC treatments were continued after wounding for a tota l of 6 days. Corneas were photographed and quantitative morphometry of the wound site was performed. Compared with saline controls, MMC sign ificantly delayed wound healing (P < 0.05) whereas 5FU did not (P > 0. 05). Compared with 5FU, MMC significantly delayed wound healing with e ither normal saline or EGF perfusion (P < 0.05). In the presence of ei ther 5FU or MMC, EGF perfusion had no significant effect on the cornea l wound-healing rate (P > 0.05). Corneal wound healing is not affected by subconjunctivally injected 5FU while it is delayed by topically ap plied MMC. EGF treatment does not overcome the inhibitory effects of M MC. EGF therapy may not be useful in the treatment of complications re lated to antimetabolite therapy.