PURPOSE: To reveal the expression profile and clinical significance of circular 
RNAs (circRNAs) in diabetic retinopathy (DR).
METHODS: Circular RNA microarrays were performed to identify DR-related 
circRNAs. Gene ontology (GO) enrichment and KEGG analysis was performed to 
determine the biologic modules and signaling pathway. TargetScan and miRana 
program was used to predict circRNA/miRNA interaction. Quantitative PCR assays 
were performed to detect circRNA expression pattern in clinical samples. Ki67 
staining, Transwell, tube formation, and spheroid sprouting assays were 
performed to investigate the role and mechanism of circRNA in endothelial 
angiogenic function.
RESULTS: A total of 529 circRNAs were aberrantly expressed in diabetic retinas. 
The host genes of differentially expressed circRNAs were targeted to ATP binding 
(biologic process); extracellular exosome (cellular component); and 
intracellular signal transduction (molecular function). Circ_0005015 was 
verified to be upregulated in the plasma, vitreous sample, and fibrovascular 
membranes of DR patients. Circ_0005015 facilitated retinal endothelial 
angiogenic function via regulating endothelial cell proliferation, migration, 
and tube formation. Circ_0005015 acted as miR-519d-3p sponge to inhibit 
miR-519d-3p activity, leading to increased MMP-2, XIAP, and STAT3 expression.
CONCLUSIONS: circRNAs are involved in DR pathogenesis, and thus serve as 
potential biomarkers of DR diagnosis.