VITAMIN-E SUCCINATE INHIBITS PROLIFERATION AND MIGRATION OF RETINAL-PIGMENT EPITHELIAL-CELLS IN-VITRO - THERAPEUTIC IMPLICATION FOR PROLIFERATIVE VITREORETINOPATHY

Background: Retinal pigment epithelial (RPE) cells play an important r ole in proliferative vitreoretinopathy (PVR). Vitamin E succinate is a n ester form of a potent biological antioxidant, vitamin E, and has un ique effects on various cells, We examined the effect of vitamin E suc cinate on proliferation and migration of cultured bovine RPE cells, si nce these are critical steps in the development of PVR. Methods: Bovin e RPE cells were cultured in minimal essential medium (MEM) containing 10% fetal calf serum (MEM-10). Cells were incubated with MEM-IO conta ining 25 mu M vitamin E, vitamin E succinate, butylated hydroxytoluene (BHT) or d-mannitol. Cell proliferation was assessed by counting cell numbers on days 2, 4 and 6. H-3-Thymidine uptake was also examined in RPE cells incubated with various forms of vitamin E - vitamin E, vita min E succinate, Trolox, gamma-tocopherol, vitamin E acetate, vitamin E phosphate, vitamin E nicotinate - or antioxidants - BHT or d-mannito l (25 mu M each). RPE cell migration was studied as follows: A small a rea (5X15 mm) of confluent cultured RPE cells was denuded using a stra ight razor blade and incubation was continued for 20 h with MEM-10 con taining vitamin E, vitamin E succinate, gamma-tocopherol or BHT. The n umber of cells that migrated into the denuded area from the wound edge in each microscopic field (x20) was counted and expressed as a percen tage of control (MEM-IO alone). Results: The antioxidants, vitamin E a nd BHT, stimulated RPE cell proliferation and H-3-thymidine incorporat ion compared with the control, while vitamin E succinate significantly inhibited both proliferation and H-3-thymidine uptake (IC50, 23 mu M) . Other forms of vitamin E or d-mannitol had no effect. Neither vitami n E nor BHT had a significant effect on RPE cell migration (108.2% and 112.6% of control, respectively), but vitamin E succinate inhibited m igration (58.3%). Cell viability, assessed by the trypan blue dye excl usion test, was not impaired by a 3-day incubation with 50 mu M of vit amin E succinate. Conclusions: An ester form of a physiological antiox idant, vitamin E succinate, inhibits RPE cell proliferation acid migra tion without causing cellular toxicity. These findings suggest its the rapeutic potential for the pharmacological treatment of PVR.