MicroRNA (miRNA) in the Pathogenesis of Diabetic Retinopathy: A Narrative Review.

Diabetic retinopathy (DR) is the most common microvascular complication associated with diabetes mellitus and represents a leading cause of visual impairment worldwide. Inflammation, endothelial dysfunction, angiogenesis, neurodegeneration, and oxidative stress are key pathogenic processes in the development and progression of DR. Numerous microRNAs (miRNAs) show altered expression in DR and modulate critical biological pathways. Pro-inflammatory miRNAs such as miR-155 and miR-21 promote cytokine release and vascular inflammation, while miR-146a acts as a negative regulator of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. MiR-126 and miR-21 regulate endothelial integrity and angiogenesis through pathways involving Vascular Endothelial Growth Factor (VEGF). MiR-200b and miR-126 are downregulated in DR, leading to increased neovascularization via activation of the VEGF/ Mitogen-Activated Protein Kinase (MAPK) cascade. Apoptotic processes are affected by miR-195, which downregulates Sirtuin 1 (SIRT1) and B-cell lymphoma 2 (Bcl-2), promoting retinal cell death, while miR-29b downregulation permits upregulation of the transcription factor SP1, enhancing caspase-mediated apoptosis in Müller cells and endothelial cells. miRNAs collectively modulate an intricate regulatory network that contributes to the underlying mechanisms of diabetic retinopathy development and progression. This narrative review aims to summarize knowledge regarding the mechanisms miRNAs mediating pathogenetic mechanisms of DR.