INHIBITION BY RAPAMYCIN OF PDGF-INDUCED AND BFGF-INDUCED HUMAN TENON FIBROBLAST PROLIFERATION IN-VITRO

Purpose: Fibrosis of subconjunctival tissues is a major cause of bleb failure following glaucoma filtration surgery. The aim of the present investigation was to demonstrate the effect of Rapamycin, a clinically relevant macrolide antibiotic with potent immunosuppressive propertie s, on human Tenon fibroblast proliferation induced by platelet-derived growth factor and basic fibroblast growth factor. Methods: Primary Te non fibroblast cultures were derived from patients undergoing trabecul ectomies or routine cataract extractions. Rapamycin was added in conce ntrations of 0.1-100 ng/ml with or without 3-30 ng/ml of porcine plate let-derived growth factor or of human recombinant basic fibroblast gro wth factor. Two days after treatment, the cells were examined and coun ted. The results were expressed as the percent of cell growth in treat ed culture relative to its untreated control. Results: Rapamycin was n ot cytotoxic at any of the concentrations tested, Inhibition of platel et-derived growth factor-induced Tenon fibroblast proliferation occurr ed with all doses of Rapamycin, the most marked effect being observed with 30 ng/ml (60% inhibition, p < 0.001). In contrast, optimal inhibi tion of basic fibroblast growth factor-induced proliferation was only 37% (p < 0.01), achieved with 10 ng/ml of the peptide. Conclusion: Rap amycin potently inhibits platelet-derived growth factor-induced fibrob last proliferation in vitro without any apparent cytotoxicity. It may eventually prove to be a useful adjunct to glaucoma filtration surgery .