The preclinical studies on circRNA are the most popular topic these days, including many latest reports about diabetic retinophathy (DR) for both treatment and diagnosis. This review aims to investigate the treatment effects of circRNAs on DR, its potential mechanism and cell targeting in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and finally discover the optimal targeting sequence of circRNAs for further clinical application. A literature search for all potential reference articles published online until 2021 was conducted in electronic databases of Pubmed, ScienceDirect and China National Knowledge Infrastructure. This systematic review has given rise to many impressive findings of circRNAs on the treatment of DR by regulating the proliferation, migration, tube formation, apoptosis, and inflammatory response of various cells in the retina. The functional exploration of circRNAs in DR will provide new ideas or target molecules for the prevention and control of DR development. According to their effects on rodent DR model, circZNF532 and circPWWP2A were the most hopeful targets with major effects on pericytes, followed with circZNF609 and circHIPK3. Many more circRNAs would be prospectively promised to optimize the clinical outcomes of circRNAs in DR.

ABBREVIATIONS: DM: diabetes mellitus; DR: diabetic retinopathy; HRVECs: human retinal vascular endothelial cells; IL-6: interleukin 6; IL-1β: interleukin 1β; TNF-α: tumor necrosis factor α; VECs: human retinal vascular endothelial cells