97th DOG Annual Meeting 1999

K684

MULTIDRUG RESISTANCE RELATED PROTEINS IN HUMAN TENON FIBROBLASTS

J. M. Esser, H. Mietz, M. Weller, T. T. Luther, P. Esser

Multidrug resistance (MDR) is the phenomenon of cross-resistance to a wide variety of structurally and pharmacologically unrelated compounds in cells selected for resistance against a single drug. Here we sought to examine whether two multidrug resistance related proteins, i.e. lung resistance protein (LRP) and multidrug resistance associated protein (MRP), are expressed in tenon tissue of glaucoma patients. Moreover, we tried to assess the expression of these proteins in cultured human tenon fibroblasts.

Methods: Expression of LRP and MRP was investigated in surgically removed tenon tissue (n=10) by immunohistochemistry using a commercially available monoclonal antibody. MRP and LRP expression by cultured tenon fibroblasts was assessed by RT-PCR and flow cytometric analysis.

Results: LRP expression was detected in 8 of 10 tenon specimen. Positive staining for MRP could be obtained in 5 of 10 specimen. Strongest staining for LRP was observed in patients, who had undergone previous surgery with mitomycin C (MMC). Exposure of cultured human tenon fibroblasts for 2 weeks to subtoxic concentrations of MMC induced a slight upregulation of LRP at the protein level, but not at the mRNA level, suggesting a translational rather than transcriptional mechanism in LRP expression. MRP expression was not influenced by MMC-treatment.

Discussion: Besides p-glycoprotein, other multidrug resistance related proteins are present in tenon tissue of glaucoma patients. The presence of these proteins might help to explain the failure of filtration surgery in cases of complicated glaucoma where adjuvant chemotherapeutic agents like MMC are used.

Universitäts-Augenklinik Köln, Joseph-Stelzmann Str. 9, D-50931 Köln


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