Exosomes enriched with microRNA mimics or inhibitors: A possible treatment modality for diabetic retinopathy

Abstract

Diabetic retinopathy is a leading cause of vision impairment and blindness in individuals with diabetes. Under conditions of chronic hyperglycemia and retinal hypoxia, pathological angiogenesis develops, increasing the risk of retinal hemorrhage. Disease progression is driven by oxidative stress and chronic inflammation, which activate complex signaling cascades that promote neovascularization. Diabetic macular edema, caused by leakage from damaged retinal vessels, is the primary cause of vision loss in diabetic retinopathy. Based on the presence of retinal neovascularization, diabetic retinopathy is classified as nonproliferative or proliferative diabetic retinopathy. Current therapies, including laser photocoagulation, intravitreal anti-vascular endothelial growth factor injections, and vitreoretinal surgery, can only partially preserve vision, underscoring the importance of early intervention to control abnormal angiogenesis. Exosomes are lipid bilayer vesicles 30–150 nm in diameter that carry bioactive molecules such as proteins, mRNAs, miRNAs, and other noncoding RNAs. They are released by many cell types, including immune cells and retinal pigment epithelium, a major source of vascular endothelial growth factor in retinopathy. This review summarizes human studies investigating the therapeutic potential of exosomes in diabetic retinopathy, with a focus on miRNAs involved in angiogenesis and their utility as biomarkers and treatment targets. Altered expression of exosomal miRNAs, including downregulated miR-204-5p in vitreous humor and upregulated miR-15a in tears and vitreous humor, may serve as diagnostic biomarkers. Exosomes derived from bone marrow mesenchymal stem cells and ARPE19 cells suppress endothelial cell proliferation, migration, and tube formation. Modulation of specific miRNAs further reduces angiogenesis. Collectively, these findings suggest that miRNA-modulated exosomes represent a promising cell-free therapeutic strategy for proliferative diabetic retinopathy, although challenges related to exosome yield and purification remain.