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R. Amer, L. Rabinowich, I. Puxeddu, F. Levi-Schaffer, A. Solomon; Comparable Inhibitory Effects of Mycophenolic Acid and Mitomycin-C on Pterygium and Normal Human Tenon Fibroblasts. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6035.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effects of mycophenolic acid (MPA) on normal human tenon fibroblast (HTF) proliferation after stimulation with fibrogenic cytokines, and to compare the efficacy of MPA to mitomycin (MMC) and dexamethasone (DXM) on pterygium fibroblasts (PFB) and HTF.
HTF were obtained from tissue explants during strabismus or pterygium surgery. Proliferation of subconfluent fibroblasts was assessed by using the (³H) thymidine-incorporation assay. Fibroblast proliferation was assessed following TGF-β1 (10ng/ml) or b-FGF stimulation (10ng/ml). MPA (10-8-10-3 M) was added to the cultures for 48 hours. Cell cultures were also incubated with either MPA, MMC (10-8, 10-6-10-3 M) or DXM (100µg/ml, 200µg/ml, 400µg/ml). Fibroblast apoptosis and necrosis induced by MPA was assessed by the addition of annexin-V and propidium iodide stains, and by evaluating positively stained cell populations with FACS.
MPA showed a concentration-dependent inhibition of proliferation of PFB. At the maximal MPA concentration of 10-3M, PFB proliferation was significantly inhibited by 94.2% (from a mean of 413.5 cpm/well in cells without MPA to 24 cpm/well with MPA). Likewise, MMC (10-3M) inhibited PFB proliferation by 96.15% (from a mean of 804.56 cpm/well in cells incubated without MMC to 31 cpm/well with MMC). MPA (at optimal concentrations of 10-3 - 10-6 M) significantly inhibited TGF-β1and bFGF -induced HTF proliferation. At MPA concentration of 10-3M, bFGF -induced fibroblast proliferation was inhibited by 99.5% (p<0.001). The antiproliferative effect of MPA was comparable to that of MMC and DXM. MMC (10-3M) significantly inhibited HTF proliferation by 98.52% (p<0.001). DXM (400µg/ml ) significantly inhibited HTF proliferation by 77.1% (p<0.001). MPA did not cause apoptosis nor did it induce significant necrosis of the fibroblast populations under study.
Mycophenolic acid suppressed activated fibroblast proliferation by cultured normal fibroblasts. It showed comparable efficacy to conventional antifibrotic agents when applied to pterygium and normal tenon fibroblasts. This effect was not the result of cytotoxic or apoptotic effect of the drug. This effect can be utilized to modify the course of cicatrizing ocular surface conditions and to modulate the postoperative fibrotic response after pterygium excision.
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