97th DOG Annual Meeting 1999

P580

MULTIDRUG RESISTANCE RELATED PROTEINS IN PROLIFERATIVE VITREORETINOPATHY

P. Esser, N. Kociok, U. Schraermeyer, S. Grisanti, J. M. Esser, A. Hueber

The phenomenon of cross-resistance to a wide variety of structurally and pharmacologically unrelated compounds in cells selected for resistance against a single drug is described as multidrug resistance (MDR). 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 tissue samples derived from patients suffering from proliferative vitreoretinopathy (PVR). Moreover, we tried to assess the expression of these proteins in cultured human retinal pigment epithelial (RPE)-cells.

Methods: Surgical specimen (n=10) were obtained during vitrectomy for traumatic PVR. Expression of LRP and MRP was investigated by immunohistochemistry using a commercially available monoclonal antibody. MRP and LRP expression by cultured RPE-cells was assessed by RT-PCR and flow cytometric analysis.

Results: LRP expression was detected in 8 of 10 membranes. Positive staining for MRP could be obtained in 3 of 10 specimen. Exposure of cultured RPE-cells for 2 weeks to subtoxic concentrations of daunomycin 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 daunomycin treatment.

Discussion: Besides p-glycoprotein, other multidrug resistance related proteins are present in PVR membranes. The presence of these proteins might help to explain the failure of retinal reattachment surgery involving adjuvant chemotherapeutic agents like daunomycin in cases of complicated PVR.

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


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