Introduction The loss of retinal pigment epithelial (RPE) cells is associated with the etiology of diabetic retinopathy (DR). This study investigated the effects of circular RNA ZNF532 (circZNF532) on apoptosis and pyroptosis of RPE cells. Materials and Methods Blood samples were collected from patients with DR and healthy volunteers. A human RPE cell line ARPE‐19 was induced by high glucose (HG) and assayed for cell viability, apoptosis, and pyroptosis. The binding of miR‐20b‐5p with circZNF532 and STAT3 was confirmed by a luciferase activity assay. A mouse model of diabetic retinopathy was established. Results CircZNF532 and STAT3 were upregulated but miR‐20b‐5p was downregulated in the serum samples of patients with DR and HG‐induced ARPE‐19 cells. Elevated miR‐20b‐5p or CircZNF532 knockdown enhanced proliferation but reduced apoptosis and pyroptosis of ARPE‐19 cells. CircZNF532 sponged miR‐20b‐5p and inhibited its expression. STAT3 was verified as a target of miR‐20b‐5p. MiR‐20b‐5p modulated ARPE‐19 cell viability, apoptosis, and pyroptosis by targeting STAT3. Mice with STZ‐induced diabetes showed elevated expressions of circZNF532 and STAT3 but decreased the level of miR‐20b‐5p compared with the controls. Knockdown of circZNF532 inhibited apoptosis and pyroptosis in mouse retinal tissues. Conclusion CircZNF532 knockdown rescued human RPE cells from HG‐induced apoptosis and pyroptosis by regulating STAT3 via miR‐20b‐5p.

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