DR is a common complication of diabetes in which every cell type in the retina is affected or damaged, resulting in irreversible vision loss. Although DR was classically considered a vascular disease, evidence now supports DR as a neurovascular disease, in which neuronal damage is present much earlier than vascular pathology or clinically observable abnormalities. The mechanisms by which neurons are damaged in early DR are linked to the effects of reactive oxygen species, apoptotic signaling by capase-dependent, caspase-independent, and Fas/FasL pathways and glial cell reactivity resulting in excitotoxicity, neurotrophin imbalance, and breakdown of neurovascular coupling. Although some features of neurodegeneration in early DR have been uncovered, research must continue to elucidate gaps in understanding the neurovascular unit, effects of neurotrophins on the diabetic retina, and the exact mechanisms by which ROS encourage neuronal apoptosis.
These mechanisms are crucial to prevent progression of DR and vision loss. Currently treatment for DR treats vascular symptoms but cannot stall the course of the disease. As discussed in this paper, strict glycemic control in early stages of DR is not sufficient to prevent progression of neuronal apoptosis. Thus understanding mechanisms of neurodegeneration in DR must guide future avenues of treatment development.
Jha, Sonal V.; Valdez, Laura; and Tsin, Andrew T C, "Cellular and Molecular Mechanisms of Neuronal Degeneration In Early Stage Diabetic Retinopathy" (2021). School of Medicine Publications and Presentations. 435.
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