CircMETTL3 Inhibits H 2 O 2 ‐Induced Senescence, Oxidative Stress, and DNA Damage in ARPE‐19 Cells via miR‐100/BMPR2 Axis

Background Age‐related macular degeneration (AMD) is a common degenerative eye disease that eventually leads to irreversible vision loss. CircRNAs have received increasing attention for their regulatory role in AMD. In this study, whole transcriptome sequencing identified differentially expressed circRNA (circMETTL3) in AMD. Previous studies have unlocked the potential mechanism of circMETTL3 in cancer, but its role in AMD has not been studied. Methods ARPE‐19 cells treated with H 2 O 2 were used as the AMD cell model. The senescence, oxidative stress, and DNA damage of ARPE‐19 cells were determined by SA‐β‐gal staining, DCFH‐DA staining, and IF assay. The levels of RPE‐specific markers or mRNA levels were assessed using western blot assay. The potential mechanism of circMETTL3 was investigated by luciferase reporting assay and RIP assay. Results CircMETTL3 was revealed to decrease in AMD cell models. The addition of circMETTL3 decreased SA‐β‐gal staining and ROS production and facilitated cell viability in H 2 O 2 ‐treated ARPE‐19 cells. Moreover, γH2AX and KRT18 levels were suppressed, and TJP1, BEST1, and CTNNB1 protein levels were increased by circMETTL3 addition. In addition, circMETTL3 could bind to and negatively regulate miR‐100. Overexpression of miR‐100 exacerbated senescence, oxidative stress, and DNA damage in H 2 O 2 ‐treated ARPE‐19 cells, which reversed the effects of circMETTL3. Furthermore, BMPR2 was targeted by miR‐100. Overexpression of BMPR2 inhibited H 2 O 2 ‐induced cell damage in ARPE‐19 cells, which reversed the effects of miR‐100. Conclusions In sum, these findings demonstrated that the circMETTL3/miR‐100/BMPR2 axis plays a vital regulatory role in AMD development.