Figure 7.

METTL3 silencing inhibits EMT and subretinal fibrosis induced by laser photocoagulation. (A) Western blotting analysis of E-cadherin and α-SMA was conducted to evaluate the EMT process upon METTL3 knockdown in vivo. (B) OCT images of individual lesions were acquired 28 days after laser induction, presenting the smaller area of subretinal lesions caused by METTL3 knockdown (n = 10 for each group). Scale bar, 100 µm. (C) Immunofluorescence staining on RPE–choroid flatmounts showed a reduction in the volume of Fibronectin-positive lesions in the shRNA METTL3 group (n = 10 for each group). Scale bar, 200 µm. (D) Schematic representation of the METTL3–m⁶A–HMGA2 axis in subretinal fibrosis. During the formation of subretinal fibrosis, METTL3 is upregulated in RPE cells undergoing EMT. METTL3 promotes the stability of HMGA2 mRNA via m⁶A modification in 3′UTR, and the METTL3–m⁶A–HMGA2 axis positively regulates the induction of potent EMT-TFs, including SNAIL and SLUG. Data present mean ± SD. Student's t-test, *P < 0.05, **P < 0.01, ***P < 0.001.