Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early non-proliferative stage, in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium and inflammation. This is conducive to over-compensatory pathological neovascularization associated with advanced, proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation and dysregulation of neurovascular crosstalk are responsible in part for vascular abnormalities in both early non-proliferative DR and advanced, proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular crosstalk and its dysregulation in DR, and their potential therapeutic implications.
- diabetic retinopathy
- retinal degeneration
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology