Aim: Age-related macular degeneration(AMD)is the leading cause of irreversible blindness in developed countries.Senescence of retinal pigment epithelium (RPE)plays a critical role in age-related eye diseases,such as AMD.However,no effective clinical drugs have been applied to prevent or delay RPE senescence.Emodin is an active component of Chinese Medicine rhubarb.Our study was performed to determine if Emodin participated in RPE senescence.Methods: Oxidative stress-induced premature senescence models were established in primary RPE cells and human ARPE-19 cells upon H2O2 or tert-BHP treatment.Senescence-associated β-galactosidase(SA β-gal)staining and LDH viability assay were performed to determine senescent RPE cells.Immunofluorescence staining was used to detect protein sub-cellular localization.Luciferase reporter assay and RNA-IP were applied to demonstrate the association between microRNA and its target.Results: We found that Emodin significantly inhibited H2O2-and tert-BHP-induced RPE senescence.Emodin apparently decreased p21/FOXO1 but not p53 signaling pathway.FOXO1 expression was dramatically suppressed by Emodin.FOXO1 cellular localization and its transcriptional level were not altered by Emodin.However,Emodin apparently inhibited FOXO1 3UTR activity.Bioinformatics analysis found that FOXO1 3UTR included one potential miR-273 target site conserved in humans and mice.Luciferase repoter assay and RNA-IP demonstrated that miR-273 was responsible for the inhibitory effect of Emodin on FOXO1.Importantly,Emodin inhibited RPE senescence was apparently diminished upon FOXO1 overexpression in ARPE-19 cells.Conclusions: Our study,for the first time,demonstrated that Emodin prevented oxidative stress-induced RPE senescence,strongly suggesting that Emodin may be exploited clinically to prevent or inhibit age-associated eye diseases.