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Mitomycin C induces multidrug resistance in glaucoma surgery
Arno Hueber1, Johannes M Esser, Norbert Kociok
1Centre of Ophthalmology, University of Cologne, Cologne, Germany. arno.hueber@uni-koeln.de
Summary
Mitomycin C treatment can cause drug resistance in eye surgery by increasing P-glycoprotein. Verapamil or 5-fluorouracil may improve success rates in repeat trabeculectomies.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Trabeculectomy is a glaucoma surgery that sometimes fails despite using mitomycin C.
- Investigating the development of multidrug resistance in Tenon fibroblasts due to mitomycin C exposure.
Purpose of the Study:
- To determine if low-dose mitomycin C induces a multidrug resistance phenotype in human Tenon fibroblasts in vitro.
- To assess if mitomycin C treatment during prior glaucoma surgery leads to P-glycoprotein expression in vivo.
Main Methods:
- Human Tenon fibroblasts were treated with low-dose mitomycin C, then exposed to varying concentrations of mitomycin C with or without verapamil.
- P-glycoprotein expression was analyzed using flow cytometry, immunoblotting, and RT-PCR.
- Tenon tissue from patients with and without prior mitomycin C exposure was examined via immunohistochemistry.
Main Results:
- Pre-treatment with low-dose mitomycin C induced partial resistance, which was reversed by verapamil.
- Mitomycin C increased P-glycoprotein expression but not mdr-1 mRNA levels.
- P-glycoprotein was detected in Tenon tissue from patients previously treated with mitomycin C, but less so in those without prior exposure.
Conclusions:
- Mitomycin C-induced P-glycoprotein expression may contribute to trabeculectomy failures after repeated use.
- Concomitant use of verapamil or alternative agents like 5-fluorouracil could enhance the success of repeat trabeculectomies.
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