BACKGROUND: Diabetic retinopathy, a vascular complication of diabetes mellitus, 
is the leading cause of visual impairment and blindness. circRNAs act as 
competing endogenous RNA, sponging target miRNA and thus influencing mRNA 
expression in vascular diseases. We investigated whether and how circDNMT3B is 
involved in retinal vascular dysfunction under diabetic conditions.
METHODS: qRT-PCR was performed to detect expression of circDNMT3B, miR-20b-5p, 
and BAMBI in retinal microvascular endothelial cells under diabetic conditions. 
Western blot, Cell Counting Kit-8, Transwell, Matrigel tube formation, and 
retinal trypsin digestion assays were conducted to explore the roles of 
circDNMT3B/miR-20b-5p/BAMBI in retinal vascular dysfunction. Bioinformatics 
analysis and luciferase reporter, siRNA, and overexpression assays were used to 
reveal the mechanisms of the circDNMT3B/miR-20b-5p/BAMBI interaction. 
Electroretinograms were used to evaluate visual function.
FINDINGS: Upregulation of miR-20b-5p under diabetic conditions promoted 
proliferation, migration, and tube formation of human retinal microvascular 
endothelial cells (HRMECs), which was mediated by downregulated BAMBI. Under 
diabetic conditions, circDNMT3B, which acts as a sponge of miR-20b-5p, is 
downregulated. circDNMT3B overexpression reduced retinal acellular capillary 
number and alleviated visual damage in diabetic rats. Changes in expression of 
circDNMT3B and miR-20b-5p were confirmed in the proliferative fibrovascular 
membranes of patients with diabetic retinopathy.
INTERPRETATION: Downregulation of circDNMT3B contributes to vascular dysfunction 
in diabetic retinas through regulating miR-20b-5p and BAMBI, providing a 
potential treatment strategy for diabetic retinopathy.
FUNDING: National Natural Science Foundation of China, National Key Basic 
Research Program of China, Shanghai Municipal Science and Technology Major 
Project, and ZJLab.