The Role of Fractalkine in Diabetic Retinopathy: Pathophysiology and Clinical Implications.

Abstract

Diabetic retinopathy (DR) is a complication of diabetes, characterized by progressive microvascular dysfunction that can result in vision loss. Chronic hyperglycemia drives oxidative stress, endothelial dysfunction, and inflammation, leading to retinal damage and complications such as neovascularization. Current treatments, including anti-VEGF agents, have limitations, necessitating the exploration of alternative therapeutic strategies. Fractalkine (CX3CL1), a chemokine with dual roles as a membrane-bound adhesion molecule and a soluble chemoattractant, has emerged as a potential therapeutic target. Its receptor, CX3CR1, is expressed on immune cells and mediates processes such as immune cell recruitment and microglial activation through intracellular signaling pathways. In DR, soluble fractalkine plays critical roles in retinal inflammation, angiogenesis, and neuroprotection, balancing tissue damage and repair. In DR, elevated fractalkine levels are associated with retinal inflammation and endothelial dysfunction. Experimental studies suggest that fractalkine deficiency exacerbates the severity of diabetic retinopathy (DR), whereas exogenous fractalkine appears to reduce inflammation, oxidative stress, and neuronal damage. However, its role in pathological angiogenesis within DR remains unclear and warrants further investigation. Preclinical evidence indicates that fractalkine may hold therapeutic potential, particularly in mitigating tissue injury and inflammation associated with early-stage DR.