EFFECTS OF SINGLE, SHORT-TERM EXPOSURES OF HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS TO THIOTEPA OR 5-FLUOROURACIL - IMPLICATIONS FOR THE TREATMENT OF PROLIFERATIVE VITREORETINOPATHY

Aim-To investigate the effects of single, short term (5 or 30 minutes) exposures to thiotepa or 5-fluorouracil (5-FU) on collagen lattice co ntraction and retinal pigment epithelial (RPE) cell proliferation. Met hods-Far collagen contraction studies, RPE cells seeded into free floa ting type I collagen lattices were exposed to single 5 or 30 minute tr eatments with thiotepa (0.06-4 mg/ml), or 5-FU (0.25-25 mg/ml), or pho sphate buffered saline alone as a control. For proliferation studies, RPE cell monolayers were similarly exposed to these agents. The degree of contraction, effects on cell number, and viability were determined up to 14 days after treatment. Results-Contraction of collagen lattic es containing RPE cells and proliferation of RPE cells were significan tly inhibited (p<0.05) by thiotepa and 5-FU at concentrations above 0. 06 mg/ml and 0.25 mg/ml respectively (for both 5 and 30 minute treatme nts), compared with controls. Cell death did not occur except for expo sure of the RPE cells in collagen lattices to the highest concentratio n of thiotepa (4 mg/ ml). Conclusion-It was concluded that single 5 or 30 minute exposures to thiotepa or 5-FU significantly inhibited colla gen contraction and the proliferation of RPE cells. These findings sug gest that short, single, non-toxic exposures to thiotepa or 5-FU which can be reproduced clinically may be useful in the modulation of proli ferative vitreoretinopathy.