Toxic Effects of Mitomycin-C on Cultured Ciliary Process Cells and Trabecular Meshwork Cells

Abstract

Mitomycin-C has recently become an adjunct medication for inhibition of fibroblast proliferation in glaucoma filtering procedures. Prolonged postoperative ocular hypotony has been a frequent complication of trabeculectomy with mitomycin-C. In order to characterize the hypotony mechanism, we compared the toxic effects of mitomycin-C on cultured rabbit ciliary process cells and trabecular meshwork cells. The results indicate that mitomycin-C has a more marked effect on ciliary process cells on 3H-thymidine uptake than on trabecular meshwork cells at concentrations ranging from 10(-1) to 10(-5) mg/ml after 3-, 5- and 60-min treatment, respectively. The living cells after mitomycin-C treatment were estimated with MTT assay that was converted tetrazolium dye of living cells only into insoluble purple formazan crystals within mitochondria. In the presence of mitomycin-C for 3, 5, and 60 min, the cellular MTT values in ciliary process cells were more decreased than in trabecular meshwork cells. Depolarization of the trabecular meshwork cells with 50 mM KCl led to an increase in intracellular calcium concentration, whereas application of mitomycin-C at 10(-3) mg/ml resulted in decrease of KCl-induced intracellular calcium increase. Mitomycin-C (10(-3) mg/ml) decreased cAMP concentration in ciliary process cells following 3- and 5-min treatment; however, it did not significantly affect the cellular cAMP concentration after only a 1-min exposure. Mitomycin-induced marked ladder pattern of DNA fragmentation was observed in ciliary process tissues after treatment with 10(-1) mg/ml of mitomycin-C for 3 and 5 min. However, the DNA pattern in trabecular meshwork tissues was not obviously affected by mitomycin-C. These findings from our results indicate that mitomycin-induced ocular hypotony may result from damage to both ciliary process and trabecular meshwork tissues.

Ciliary Body Toxicity of Subconjunctival Suramin Compared with Mitomycin-C in the Rabbit Eye: Determining the Toxic Concentration

“…A previous report has identified DNA fragmentation in ciliary body tissue cultures with 0.1 mg/ml MMC applied for 3 min [33] . Suramin is expected to affect only heparin-binding cells, as it is a heparin analogue, unlike antimitotic MMC, which impacts all cells with mitotic capacity.…”

Mechanism of 5-Fluorouracil-Induced Apoptosis on Cultured Corneal Endothelial Cells

“…Cell viability was measured with MTT dye following previously published procedures [16]. The MTT assay is based on the production of purple formazan from a methyltetrazolium salt by the mitochondrial enzymes of viable cells.…”

Comparison of posterior capsule opacification in rabbits receiving either mitomycin‐C or distilled water for sealed‐capsule irrigation during cataract surgery

“…In one study, the toxic dose of intracameral MMC was reported to be 0.8 mg/mL 16 . In cases of accidental access of MMC to the anterior chamber, MMC may result in damage to endothelial cell, keratocyte, ciliary process and trabecular meshwork tissues 17–19 . This suggests that DW may be sufficient to prevent PCO clinically in human eye without inadvertent toxicity of MMC.…”

“…16 In cases of accidental access of MMC to the anterior chamber, MMC may result in damage to endothelial cell, keratocyte, ciliary process and trabecular meshwork tissues. [17][18][19] This suggests that DW may be sufficient to prevent PCO clinically in human eye without inadvertent toxicity of MMC. We chose silicone IOL implantation, prone to develop PCO, and rabbit eyes that have more proliferative activity Table 2.…”