A Comparative Study of Effects of Antiproliferative Drugs on Human Retinal Pigment Epithelial Cells in Vitro

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Abstract
The effects of various antiproliferative drugs have been tested in numerous cell types in vitro, but a comparison of effects of these drugs on cultured human retinal pigment epithelium (RPE) has not been reported. We studied the effects of four most widely used antiproliferative drugs (5-FU, daunomycin, mitomycin and dexamethasone) in a new in vitro model system (cultured human RPE). Various concentrations and exposure periods were tested in four human RPE cell lines. 5-FU showed a dose-dependant growth inhibition, with an ID50 of 5.35 ± 2.38 × 10-7 M after 4 days culture. A decrease of cell number occurred relatively later, the slope of the dose-response curve was less steep than that of others. Mitomycin C showed an immediate and strong growth inhibition and cytotoxic effects, with an ID50 of 3.73 ± 0.71 × 10-9 M. RPE cultured with daunomycin showed an abrupt decrease of cell number from 10-9 M to 10-8 M, the ID value was 1.07 ± 0.23 × 10-8 M. Dexamethasone showed a biphasic effect; it stimulated cell growth at 10-7 to 10-6 M and inhibited cell growth at 10-4 M or higher, with an ID50 of 6.05 ± 1.61 × 10-3 M. The advantages and disadvantages of these drugs and the prospective clinical application of these drugs for management of proliferative vitreoretinopathy (PVR) were discussed. Development of an in vitro model using cultured human RPE to study the effects of various antiproliferative drugs can provide a rapid, safe and inexpensive method for selection of drugs used for management of proliferative vitreoretinopathy.