Multidrug resistance-associated proteins in glaucoma surgery

Background: Multidrug resistance (MDR) describes the phenomenon of cross-re sistance between different cytostatic agents which are structurally and fun ctionally dissimilar. Two recently discovered proteins, lung resistance pro tein (LRP) and the multidrug resistance-related protein (MRP) have been imp licated in the development of MDR. Since resistance to chemotherapeutic age nts is a common problem in filtration surgery, especially in cases of compl icated glaucoma, we decided to investigate the presence of MRP and LRP in s urgically removed Tenon specimens from glaucoma patients. Methods: The pres ence of MRP and LRP in surgically removed Tenon tissue (n=15) was analyzed by immunohistochemistry. The expression by cultured Tenon fibroblasts was a ssessed by reverse-transcrip- tase polymerase chain reaction (RTPCR) and fl uorocytometry. Results: LRP expression was detected in 8 of 10 Tenon specim ens. Positive staining for MRP was obtained in 5 of 10 specimens. Negative controls with non-immune mouse IgG did not display any specific staining. R T-PCR and fluorocytometry revealed constitutive expression of MRP and LRP. at the RNA and protein level respectively, that was unaltered by pretreat m ent of the cells with mitomycin C or 5-fluorouracil. Conclusion: Our result s demonstrate, that besides P-glycoprotein, other components of the MDR-sys tem are present in conjunctival fibroblasts. Future developments in the use of chemotherapeutic agents in association with of filtration surgery need to take account of the presence of these counteracting mechanisms.