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Abstract #20403 Published in IGR 10-1
Mitomycin C induces multidrug resistance in glaucoma surgery
Hueber A; Esser JM; Kociok N; Welsandt G; Lüke C; Roters S; Esser PJGraefe's Archive for Clinical and Experimental Ophthalmology 2008; 246: 297-304
BACKGROUND: Despite the adjuvant use of mitomycin C during trabeculectomy, failures still occur. We investigated whether cultured human Tenon fibroblasts exposed to low-dose mitomycin C developed a multidrug resistance phenotype in vitro, and whether mitomycin C treatment during previous filtration surgery induces P-glycoprotein expression in vivo. METHODS: Cultured human Tenon fibroblasts treated with low-dose 0.01 nM mitomycin C for 2 weeks were subsequently treated with 0.1 to 100 μM mitomycin C in the absence or presence of 4 μM verapamil, and allowed to recover for 24 hours. Low-dose mitomycin C-treated fibroblasts were analysed for P-glycoprotein expression using flow cytometry, immunoblotting, and RT-PCR for mdr-1 mRNA. In addition, fibroblasts were treated with low dose 0.1 nM 5-fluorouracil for 2 weeks and analysed for P-glycoprotein expression using flow cytometry. Expression of P-glycoprotein was analysed in surgically removed Tenon tissue (n = 30) using immunohistochemistry. Of the 30 patients, 20 had a previous trabeculectomy, of which nine had previous adjuvant therapy with mitomycin C during trabeculectomy. RESULTS: Partial resistance to mitomycin C after low-dose mitomycin C pre-treatment was significantly neutralised by the addition of verapamil. Low-dose mitomycin C up-regulated P-glycoprotein expression, but not mdr-1 mRNA expression. 5-Fluorouracil did not induce P-glycoprotein expression. P-glycoprotein expression was detected in all nine patients exposed to mitomycin C during previous trabeculectomies. Only six of 21 specimens from patients not previously exposed to mitomycin C showed faint P-glycoprotein expression. CONCLUSION: The induction of P-glycoprotein by mitomycin C could explain some failures that occur after repeated use of mitomycin C during trabeculectomy. The concomitant use of verapamil or the use of 5-fluorouracil alone could increase the success rate of repeat trabeculectomies.
Dr. A. Hueber, Centre of Ophthalmology, University of Cologne, 50931, Cologne, Germany
Classification:
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)