Mycophenolic acid suppresses human pterygium and normal tenon fibroblast proliferation in vitro.
OBJECTIVE
To investigate whether mycophenolic acid (MPA) exerts antifibrotic effects on pterygium fibroblasts (PFB) with and without stimulation with fibrogenic cytokines, and to compare the efficacy of MPA with mitomycin (MMC) and dexamethasone (DXM) on PFB and tenon fibroblasts (TFB).


METHODS
TFB and PFB were obtained from tissue explants during strabismus or pterygium surgery. Proliferation of subconfluent fibroblasts ± basic fibroblast growth factor (bFGF) (10 ng/ml) was assessed by using the (3H) thymidine-incorporation assay. Cell cultures were incubated with MPA, MMC or DXM. Apoptosis was evaluated by quantifying Annexin V and propidium iodide positive cells with flow cytometry.


RESULTS
MPA showed a concentration-dependent inhibition of proliferation of PFB ± bFGF as well as TFB ± bFGF. The antiproliferative effect of MPA was comparable with that of MMC and DXM. Short exposure of PFB to MPA under profibrogenic conditions was significantly inhibitory. No apoptotic effect was found on TFB.


CONCLUSIONS
MPA suppressed tenon and pterygium fibroblast proliferation in vitro under basal and profibrogenic conditions. It was comparable with MMC under long-term exposure, but MMC was more suppressive under short-term exposure. MPA may be safer than MMC due to a more specific mechanism of action and lack of cytotoxicity. Further investigation is warranted regarding MPA concentrations that will lead to a potent antiproliferative effect in vivo.
Amer
Radgonde
R
Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel. radgondeamer@yahoo.com
Rabinowich
Liane
L
Maftsir
Genia
G
Puxeddu
Ilaria
I
Levi-Schaffer
Francesca
F
Solomon
Abraham
A
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000494:pharmacology*; D011625:Pterygium / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D013285:Strabismus / Q000473:pathology / Q000601:surgery
D016222:Fibroblast Growth Factor 2; D016685:Mitomycin; D003907:Dexamethasone; D009173:Mycophenolic Acid