The Toxic and Morphologic Effects of Mitomycin-C, 5-FU and Genistein on Rabbit Corneal Endothelium

ABSTRACT

PURPOSE: We determined the toxic and morphologic effects of the anti-proliferative drugs, mitomycin-C (MMC), 5-fluorouracil (5-FU) and genistein on rabbit corneal endothelium. METHODS: After intramuscular anesthesia, each drug of different concentrations (MMC at 0.05, 0.1, and 0.2 mg/ml; 5-FU at 5, 10, and 50 mg/ml; and genistein at 0.013, 0.027, and 0.054 mg/ml) was perfused into the anterior chamber of 54 white rabbits (108 eyes). The same amount of balanced salt solution was perfused into control eyes. The corneal thickness was measured before perfusion and 15 min, 30 min, 45 min, 1 h, and 24 h after perfusion. Corneal samples were prepared at 24 h after perfusion to determine the changes in corneal thickness and to observe morphologic changes of corneal endothelium under scanning electron microscope (SEM). RESULTS: A significant increase in corneal thickness was observed. Destruction of corneal endothelial cell structure was seen under scanning electron microscope at 24 h after perfusion with MMC at 0.2 mg/ml for 1, 3, and 5 min, and at 0.1 mg/ml for 5 min; and 5-FU at 50 mg/ml for 5 min into the anterior chamber. However, no significant difference was seen in corneal thickness or in corneal endothelial morphology at 24 h after perfusion with genistein. CONCLUSIONS: To avoid morphologic changes of the cornea, we recommend the anterior chamber perfusion of MMC at 0.1 mg/ml between 1 and 2 min, 5-FU at 10 mg/ml between 3 and 5 min, and genistein at 0.027 mg/ml for 5 min. Genistein at low concentrations showed no morphologic change in the cornea, suggesting the possible clinical use with safety.