Multi-Omics Insights into Systemic Molecular Alterations and Emerging Therapeutic Targets in Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is a vision-threatening complication of diabetes mellitus and one of the leading causes of blindness among working-age adults globally. It is characterised by progressive microvascular damage, neurodegeneration, and inflammation within the retina. Current clinical management relies on anti-vascular endothelial growth factor (VEGF) therapy and laser photocoagulation, which target late-stage vascular changes but fail to address the underlying systemic and molecular drivers of early disease. Moreover, diagnostic strategies remain largely imaging-based, with limited integration of molecular biomarkers that could facilitate early detection or personalized intervention. In recent years, multi-omics technologies, including metabolomics and proteomics, have emerged as powerful tools to unravel the complex molecular landscape of DR. These approaches have identified key dysregulated pathways, like the polyol pathway, and chronic inflammatory signalling, alongside candidate biomarkers in plasma, and retinal tissue. Despite this progress, clinical translation remains limited due to heterogeneity in findings and gaps in longitudinal validation. This review integrates recent multi-omics discoveries relevant to DR pathogenesis, highlights emerging systemic and retinal biomarkers, and evaluates potential therapeutic targets beyond VEGF. By integrating evidence from human and animal studies, we outline how omics-informed insights can inform risk stratification, guide therapies, and support a shift toward personalized management of DR.