The exosome-transmitted lncRNA LOC100132249 induces endothelial dysfunction in diabetic retinopathy

Diabetic retinopathy (DR), one of the most common microangiopathic complications in diabetes mellitus, causes severe visual damage among working-age populations. Retinal vascular endothelial cells, the key cell type in DR pathogenesis, are responsible for abnormal retinal angiogenesis in advanced stages of DR. The roles of exosomes in DR have been largely unknown. In this study, we report the first evidence that exosomes derived from the vitreous humor of patients with proliferative diabetic retinopathy (PDR-exo) promote proliferation, migration and tube formation of human retinal vascular endothelial cells (HRVECs). We identified lncRNA LOC100132249 enrichment in PDR-exo via high-throughput sequencing. This lncRNA, also mainly derived from HRVECs, promoted angiogenesis both in vitro and in vivo. Mechanistically, LOC100132249 acted as a competing endogenous sponge of microRNA-199a-5p (miR-199a-5p), thus regulating the endothelial-mesenchymal transition (EndMT) promoter SNAI1 via activation of the Wnt/β-catenin pathway, and ultimately resulting in endothelial dysfunction. In conclusion, our findings underscored the pathogenic role of endothelial-derived exosomes via the LOC100132249/miR-199a-5p/SNAI1 axis in DR angiogenesis, and may shed light on new therapeutic strategies for future treatment of DR.