CIS-HYDROXYPROLINE INHIBITS PROLIFERATION, COLLAGEN-SYNTHESIS, ATTACHMENT, AND MIGRATION OF CULTURED BOVINE RETINAL-PIGMENT EPITHELIAL-CELLS

Purpose. Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) and o ther cells into the vitreous cavity. The PVR membrane formation also i s associated with collagen production by RPE. The authors examined the effect of a proline analog, cis-hydroxyproline (CHP), on proliferatio n, collagen synthesis, attachment, and migration of bovine RPE in vitr o. Methods. The effect of CHP on cell proliferation was determined as a function of dosage and days in culture by counting the cell numbers on days 3, 6, and 9. Collagen synthesis was determined by trichloroace tic acid precipitation of the radiolabeled samples before and after ba cterial collagenase digestion. The attachment assay involved type I co llagen or fibronectin substrates or both (2.5 mu g/well). For migratio n experiments, RPE cells were removed from a defined area of a conflue nt culture, and migration was quantitated by counting the number of ce lls migrating into the denuded area over 30 hours. Results. The additi on of CHP inhibited RPE proliferation in both a dose- and a time-depen dent manner; collagen synthesis, attachment, and migration also were i nhibited by CHP in a dose-dependent manner. When the culture plates we re coated with collagen, <100 mu g/ml of CHP had no effect on cell att achment Higher doses of CHP resulted in mild inhibition of attachment on collagen-coated plates. Simultaneous addition of L-proline to the c ultures resulted in blockade of these inhibitory effects on proliferat ion, collagen synthesis, attachment, and migration. Conclusions. The r esults show that RPE functions critical to the development of PVR are inhibited by CHP, suggesting the possibility that this drug may have p otential clinical application.