Metformin inhibits development of diabetic retinopathy through microRNA-497a-5p

Metformin is an AMP-activated protein kinase activator that is widely prescribed for treating type 2 diabetes. Recently, metformin was reported to slow down the development and alleviate the severity of diabetic retinopathy (DR). However, the underlying mechanisms remain unclear. Here, we used an alloxan-induced diabetes mouse model to study the effects of metformin on the development of DR as well as the mechanisms. We found that DR was induced in alloxan-treated mice 10 weeks after alloxan treatment, and treatment of metformin did not prevent the occurrence of alloxan-induced diabetes. However, metformin significantly alleviated the severity of DR, seemingly through attenuating the retina neovascularization. Moreover, the total vascular endothelial cell growth factor A (VEGF-A) mRNA in mouse eyes was not altered by metformin, but the protein levels was decreased. Further analysis showed that metformin may inhibit the VEGF-A protein translation through inducing a VEGF-A-targeting microRNA, microRNA-497a-5p, resulting in reduced retina neovascularization. Thus, our study suggests a previously unappreciated role of metformin in the prevention of development of DR.