Retinal pigment epithelial cells secrete miR-202-5p-containing exosomes to protect against proliferative diabetic retinopathy

Previous studies have reported that endothelial-to-mesenchymal transition (EndoMT) contributes to pathological fibrosis in proliferative diabetic retinopathy (PDR). The hypothesis of our study was that exosomes from high glucose (HG)-treated ARPE19 cells reprogram endothelial cell behavior in HG conditions by transferring their genetic contents. Our study showed that ARPE19-derived exosomes were internalized by human umbilical vein endothelial cells (HUVECs). Additionally, miR-202-5p, a miRNA known to target TGFβR2, was enriched in ARPE19-derived exosomes. A dual luciferase reporter assay, qPCR, and western blotting were used to characterize the expression of miR-202-5p and phosphorylation of the TGF/Smad pathway proteins. We showed that miR-202-5p-containing exosomes suppressed HUVEC cell growth, migration, and tube formation. Furthermore, TGFβR2 was confirmed as the target of miR-202-5p. A dual luciferase reporter assay showed that TGFβR2 expression was negatively regulated by miR-202-5p. We also showed that miR-202-5p-containing exosomes suppressed HG-induced EndoMT. These collective results suggested that ARPE-derived exosomes may serve as significant mediators of cell-to-cell crosstalk to suppress EndoMT by transferring miR-202-5p through the TGF/Smad pathway, and may be a potential treatment for PDR patients.