Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A.

作者：Quanyong Yi, Gang Deng, Nan Chen, Zhi-Sha Bai, Jianshu Yuan, Guohai Wu, Yuwen Wang, Shanjun Wu · 发表于：PubMed · 年份：2016 · 被引用次数：49 · 研究领域：Retinal Diseases and Treatments、Angiogenesis and VEGF in Cancer、Retinoids in leukemia and cellular processes

Previous studies have shown that metformin, an AMP-activated protein kinase activator widely prescribed for type 2 diabetes, is especially beneficial in cases of diabetic retinopathy (DR) with undetermined mechanisms. Here, we used a streptozotocin-induced diabetes model in mice to study the effects of metformin on the development of DR. We found that 10 weeks after STZ treatment, DR was induced in STZ-treated mice, regardless treatment of metformin. However, metformin alleviated the DR, seemingly through attenuating the retina neovascularization. The total vascular endothelial cell growth factor A (VEGF-A) in eyes was not altered by metformin, but the phosphorylation of the VEGF receptor 2 (VEGFR2) was decreased, which inhibited VEGF signaling. Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2. These findings are critical for generating novel medicine for DR treatment.