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Antimetabolite interactions with epidermal growth factor
1Department of Ophthalmology, University of Toronto, Toronto Hospital, Ontario.
Abstract:
Antimetabolites such as 5-fluorouracil and mitomycin C are known to delay wound healing. Epidermal growth factor (EGF) has been shown to accelerate corneal epithelial wound healing. This study was designed to investigate the effects of EGF on corneal epithelial healing that has been modified by antimetabolite treatment. New Zealand White rabbits were pretreated with either saline (controls) or 5-fluorouracil (5FU) injected subconjunctivally, or mitomycin C (MMC) applied topically. Circular anterior stromal wounds were created, followed by a 6-hour perfusion of normal saline or 50 micrograms/ml of EGF. Subconjunctival saline or 5FU, or topical MMC treatments were continued after wounding for a total of 6 days. Corneas were photographed and quantitative morphometry of the wound site was performed. Compared with saline controls, MMC significantly delayed wound healing (P < 0.05) whereas 5FU did not (P > 0.05). Compared with 5FU, MMC significantly delayed wound healing with either normal saline or EGF perfusion (P < 0.05). In the presence of either 5FU or MMC, EGF perfusion had no significant effect on the corneal wound-healing rate (P > 0.05). Corneal wound healing is not affected by subconjunctivally injected 5FU while it is delayed by topically applied MMC. EGF treatment does not overcome the inhibitory effects of MMC. EGF therapy may not be useful in the treatment of complications related to antimetabolite therapy.
Insights
Antimetabolites like 5-fluorouracil (5FU) and mitomycin C (MMC) impact corneal healing. Epidermal growth factor (EGF) did not improve healing delayed by these antimetabolites, suggesting limited therapeutic use.
Area of Science:
- Ophthalmology
- Wound Healing
- Pharmacology
Background:
- Antimetabolites, including 5-fluorouracil (5FU) and mitomycin C (MMC), are known to impede wound healing processes.
- Epidermal growth factor (EGF) has demonstrated efficacy in accelerating corneal epithelial wound healing.
Purpose of the Study:
- To investigate the impact of Epidermal Growth Factor (EGF) on corneal epithelial wound healing previously affected by antimetabolite treatments.
- To evaluate the efficacy of EGF in counteracting the delayed wound healing caused by 5FU and MMC.
Main Methods:
- New Zealand White rabbits received subconjunctival 5FU or topical MMC, alongside saline controls.
- Anterior stromal wounds were created and perfused with saline or EGF (50 µg/ml) for 6 hours.
- Wound healing was quantitatively assessed via morphometry over a 6-day period.
Main Results:
- Topical MMC significantly delayed corneal wound healing compared to controls (P < 0.05); subconjunctival 5FU did not (P > 0.05).
- MMC significantly delayed healing more than 5FU, irrespective of saline or EGF perfusion.
- EGF perfusion did not significantly alter corneal wound healing rates in the presence of either 5FU or MMC (P > 0.05).
Conclusions:
- Subconjunctival 5FU does not affect corneal wound healing, while topical MMC significantly delays it.
- EGF treatment failed to overcome the inhibitory effects of MMC on corneal wound healing.
- EGF therapy may not be beneficial for treating complications arising from antimetabolite use in corneal healing.