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R. Amer, I. Puxeddu, I. Anteby, F. Levi–Schaffer, A. Solomon; Supression of fibrotic responses by Mycophenolic Acid in Human Tenon Fibroblasts in Vitro . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2949.
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Purpose:To evaluate the effects of mycophenolic acid (MPA) on human tenon fibroblast proliferation, apoptosis and necrosis in vitro. Methods:Human tenon fibroblasts were obtained from tissue explants from young healthy patients during strabismus surgery. Proliferation of subconfluent fibroblasts was assessed by using the (³H) thymidine–incorporation assay. Fibroblast proliferation was assessed following TGF–ß1 stimulation at the optimal concentration of 10 ng/ml. MPA was added (10–3M to 10–8 M in DMEM with 2% fetal calf serum) to the cultures for 24 hours. 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. Results:MPA significantly inhibited TGF–ß1–induced fibroblast proliferation with optimal concentrations ranging from 10–3 to 10–6 M. The addition of MPA at 10–3 M suppressed TGF–ß1–induced fibroblast proliferation by 10% (p<0.001). MPA did not cause apoptosis nor did it induce significant necrosis of the fibroblast populations under study. Conclusions:Mycophenolic acid demonstrated a significant antiproliferative effect on human tenon fibroblasts in vitro. This effect is not the result of cytotoxic or apoptotic effect of the drug. This effect can be utilized to modify fibrotic responses of the ocular surface in various cicatrizing and allergic disorders, as well as in postoperative fibrosis in pterygium excision and in glaucoma filtering surgey.
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