Diabetic retinopathy as a sentinel of systemic vascular dysfunction: Shared molecular mechanisms with cardiovascular disease

Diabetic retinopathy (DR) and cardiovascular disease (CVD) represent interconnected complications of diabetes, bound by overlapping pathophysiological processes and epidemiological correlations. This review explores their interplay, highlighting hyperglycemia-driven oxidative stress, chronic inflammation, endothelial dysfunction, and advanced glycation end-products (AGEs)-receptor for AGEs (RAGE) axis activation, which contribute to retinal microvascular damage and systemic atherosclerosis. Severe DR markedly increases CVD risk, positioning it as a marker of vascular pathology. Therapies targeting these pathways, including intensive glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), fenofibrate, and renin-angiotensin-aldosterone system (RAAS) inhibitors, offer dual benefits, slowing DR progression and reducing CVD events. Multidisciplinary strategies integrating retinal screening with CVD risk management enhance patient care. Challenges include clarifying causality and improving risk tools. Future research should prioritize causal mechanisms, biomarkers, and personalized treatments to prevent vision loss and cardiovascular morbidity in diabetes.