Mitomycin-C concentration in cornea and aqueous humor and apoptosis in the stroma after topical mitomycin-C application: effects of mitomycin-C application time and concentration.
OBJECTIVE
To evaluate the effects of the applied mitomycin-C (MMC) concentration and application time on the aqueous MMC concentration and apoptosis in the corneal stroma.


METHODS
New Zealand white rabbits underwent mechanical epithelium debridement of the central 7.5 mm of the cornea. A sponge soaked in MMC solution was placed on the denuded corneal stroma. The effect of the exposure times ranging from 15 to 120 seconds and the different MMC concentrations ranging from 0.005% to 0.04% on the aqueous MMC concentration and the apoptosis in the stromal cells were evaluated.


RESULTS
The aqueous concentration of MMC increased linearly with increasing exposure time and MMC concentration. The correlation between the aqueous MMC concentration and the applied concentration (r = 0.809, P < 0.001) was higher than the correlation between the aqueous MMC concentration and the application time (r = 0.693, P < 0.001). Terminal deoxyribonucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling (TUNEL)-positive cells were detected in the superficial stroma of the central denuded cornea. The numbers of TUNEL-positive cells increased linearly with increasing concentrations, and the increase was statistically significant (P = 0.026). However, the numbers of TUNEL-positive cells increased only slightly with an increasing application time, and the increase was not statistically significant (P = 0.928).


CONCLUSIONS
Reducing the applied concentration or decreasing the exposure time might be a good modality for reducing the potential MMC toxicity. The applied MMC concentration had greater effects on the aqueous MMC concentration and apoptosis in the stromal cells than the exposure time.
Song
Jong-Suk
JS
Department of Ophthalmology, Korea University College of Medicine, Seoul, Republic of Korea.
Kim
Jun-Heon
JH
Yang
Minho
M
Sul
Donggeun
D
Kim
Hyo-Myung
HM
D000287:Administration, Topical; D000477:Alkylating Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001082:Aqueous Humor / Q000378:metabolism*; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D003319:Corneal Stroma / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D016685:Mitomycin / Q000493:pharmacokinetics* / Q000633:toxicity; D011817:Rabbits; D013997:Time Factors
D000477:Alkylating Agents; D016685:Mitomycin