M. Salasprato et al., INHIBITION BY RAPAMYCIN OF PDGF-INDUCED AND BFGF-INDUCED HUMAN TENON FIBROBLAST PROLIFERATION IN-VITRO, Journal of glaucoma, 5(1), 1996, pp. 54-59
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
.