Targeting choroidal vascular dysfunction via inhibition of circRNA-FoxO1 for prevention and management of myopic pathology.

Myopia has become a global public health problem due to high prevalence. Although the etiological factors of myopia have been gradually recognized, the underlying mechanism remains largely elusive. Choroidal vascular dysfunction is recognized as a critical vision-threatening complication in myopia. Circular RNAs (circRNAs) are shown as the critical regulators in many biological processes and human diseases. In this study, we investigated the role of circRNAs in choroidal vascular dysfunction in myopia. The level of circFoxO1 was significantly upregulated in myopic choroid. circFoxO1 silencing suppressed choroidal endothelial cell viability, proliferation, migration, and tube formation in vitro and alleviated choroidal vascular dysfunction in vivo and ex vivo. circFoxO1 silencing retarded the progression of myopia as shown by reduced extracellular matrix remodeling and improved refractive error and axial elongation. Mechanistically, circFoxO1 acted as the sponge of miR-145 to sequester and inhibit miR-145 activity, thereby inducing VEGFA or ANGPT2 expression. miR-145 could mimic the effects of circFoxO1 silencing on choroidal endothelial phenotypes. Collectively, intervention of choroidal vascular dysfunction via regulating circFoxO1 level is a potential strategy for the prevention and management of myopia.