Effect of brief exposure to mitomycin C on viability and proliferation of cultured human Tenon's capsule fibroblasts.
OBJECTIVE
The purpose of this study is to determine why a single intraoperative dose of mitomycin C (MMC) appears to promote the success of glaucoma filtration surgery.


METHODS
Human Tenon's capsule fibroblasts were exposed to MMC and 5-fluorouracil (5-FU) in vitro at the concentrations and durations of exposure used clinically. Cell proliferation was assessed by quantification of 3H-thymidine uptake. Cell viability was studied using a sulfarhodamine B cell protein stain and by trypan blue exclusion.


RESULTS
Neither MMC (0.4 mg/ml) nor 5-FU (40 mg/ml) were cytocidal. Both 1- and 5-minute exposures to MMC were antiproliferative. A 1-minute exposure to 0.4 mg/ml inhibited 3H-thymidine uptake by 77%. For the 5-minute exposure, 3H-thymidine uptake was inhibited by 50% at 0.06 mg/ml and by 90% at 0.4 mg/ml. For 5-FU, 3H-thymidine uptake was inhibited by 50% at 10 mg/ml and by 64% at 40 mg/ml.


CONCLUSIONS
Mitomycin C probably does not improve the success of filtration surgery by killing fibroblasts. The ability of a brief exposure to MMC to improve filtration surgery may be due to an almost complete inhibition of proliferation. Alternatively, it may be due to sustained tissue binding, effects on other components of wound healing, such as cell migration and extracellular matrix production, or effects on the vasculature. A 1-minute exposure may be as effective as a 5-minute exposure.
Jampel
H D
HD
Wilmer Ophthalmologic Institute, Johns Hopkins University School of Medicine, Baltimore.
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005123:Eye / Q000166:cytology*; D005205:Fascia / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D014130:Trabeculectomy
D016685:Mitomycin; D005472:Fluorouracil