Update in the molecular mechanism and biomarkers of diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is a serious complication of diabetes caused by long-term hyperglycemia that leads to microvascular and neuronal damage in the retina. The molecular mechanisms of DR involve oxidative stress, inflammatory responses, neurodegenerative changes, and vascular dysfunction triggered by hyperglycemia. Oxidative stress activates multiple metabolic pathways, such as the polyol, hexosamine, and protein kinase C (PKC) pathways, resulting in the production of, which in turn promote the formation of advanced glycation end products (AGEs). These pathways exacerbate vascular endothelial damage and the release of inflammatory factors, activating inflammatory signaling pathways such as the NF-κB pathway, leading to retinal cell damage and apoptosis. Additionally, DR involves neurodegenerative changes, including the activation of glial cells, neuronal dysfunction, and cell death. Research on the multiomics molecular markers of DR has revealed complex mechanisms at the genetic, epigenetic, and transcriptional levels. Genome-wide association studies (GWASs) have identified multiple genetic loci associated with DR that are involved in metabolic and inflammatory pathways. Noncoding RNAs, such as miRNAs, circRNAs, and lncRNAs, participate in the development of DR by regulating gene expression. Proteomic, metabolomic and lipidomic analyses have revealed specific proteins, metabolites and lipid changes associated with DR, providing potential biomarkers for the early diagnosis and treatment of this disease. This review provides a comprehensive perspective for understanding the molecular network of DR and facilitates the exploration of innovative therapeutic approaches.