Curcumin Inhibits Proliferation and Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells Via Multiple Pathways

Proliferative vitreoretinopathy (PVR) is a disease caused by dedifferentiation, translocation and proliferation of several types of local cells. These cells form fibrocellular membranes resulting in detachment of retinal and vision loss. PVR occurs in 8%-10% of patients undergoing primary retinal detachment (RD) surgery and becomes a major obstacle for successful RD repair. Retinal pigment epithelial (RPE) cells are among the major cells which consist of fibrocellular membranes. Reproliferation and Epithelial-mesenchymal transition (EMT) are the primary pathological alteration of RPE cells in PVR.RPE cells were treated with curcumin at different concentrations for 24, 48 and 72 hours. The viable cells were detected by MTT assay. The apoptosis of RPE was stained by Multicaspase/7-AAD and detected using flow cytometry. Cell cycle analysis was quantified by PI staining. The mRNA levels were detected by real-time PCR. The protein levels were detected by western blot.We found a compound curcumin significantly inhibited proliferation and EMT of RPE cells in vitro. Further study showed curcumin induced cell cycle arrest by activating G2 checkpoint through p53 pathway. Meanwhile, we found that curcumin suppressed the AKT, MAPK and TGF-β pathways in RPE cells which may also affect proliferation and EMT. Our research identified curcumin a potential novel agent for the PVR prevention and treatment. Curcumin induces cell cycle arrest by activating G2 checkpoint.Our results in this study also provide the insights to broaden the application of curcumin in research and probably clinics.