Diabetic retinopathy (DR) is among the most common microvascular complications of diabetes and is the leading cause of blindness among the working-age population. According to conventional perspectives, DR is a purely microvascular disease; however, accumulating evidence has demonstrated that it is fundamentally a complex condition characterized by coordinated multicellular injury to the retinal neurovascular unit. Under hyperglycemic conditions, retinal pericytes, endothelial cells, Müller cells, microglia, and retinal neurons display highly heterogeneous pathological mechanisms, which, through epigenetic reprogramming, metabolic dysregulation, oxidative stress, inflammation, and intercellular crosstalk, collectively drive the progression of DR from nonproliferative to proliferative stages. This review summarizes the cell-heterogeneous injury mechanisms and intercellular signaling networks involved and the clinical manifestations of DR progression from the perspective of cell and molecular medicine and, on the basis of relevant cellular damage targets, integrates current diagnostic and therapeutic strategies as well as emerging research directions, aiming to provide a theoretical foundation for precise targeting of multicellular pathological processes in DR.
Duan et al. (Thu,) studied this question.