MicroRNA-15b Targets VEGF and Inhibits Angiogenesis in Proliferative Diabetic Retinopathy

Background: Vascular endothelial growth factor (VEGF)-induced angiogenesis is a critical compensatory response to microvascular rarefaction in the diabetic retina that contributes to proliferative diabetic retinopathy (PDR). In this study, we sought to determine the role of specific micro ribonucleic acids (RNAs) (miRs) associated with VEGF in patients with PDR pathology. Methods: RNA sequencing was employed to detect differentially circulating miR associated with VEGF in patients with diabetes mellitus (DM), nonproliferative diabetic retinopathy (NPDR) and PDR. Quantitative real-time polymerase chain reaction was performed to measure the concentration of miR-15b in the serum of patients with DM (n = 115), NPDR (n = 47), or PDR (n = 76). The effects of miR-15b on DR and regulation of VEGF and endothelial cell function were also characterized. Results: We demonstrated that circulating miR-15b was directly associated with VEGF compared with other miRs in patients with PDR. We found a significant inverse relationship between low levels of miR-15b and high levels of VEGF in patients with PDR when compared with the DM or NPDR groups. We found that miR-15b regulates the expression of VEGF by targeting the 3'-untranslated regions to inhibit its transcription. Similarly, overexpression of miR-15b suppressed vascular abnormalities in vivo in diabetic GK rats, inhibiting endothelial tube formation and VEGF expression. Conclusion: Circulating miR-15b is associated with PDR and may be targeted to regulate VEGF expression and angiogenesis.