Diabetic retinopathy (DR) is a major contributor to permanent vision loss and blindness. Changes in retinal neurons, glia, and microvasculature have been the focus of intensive study in the quest to better understand DR. However, the impact of diabetes on the rest of the visual system has received less attention. There are reports of associations of changes in the visual system with preclinical and clinical manifestations of diabetes. Simultaneous investigation of the retina and the brain may shed light on the mechanisms underlying neurodegeneration in diabetics. Additionally, investigating the links between DR and other neurodegenerative disorders of the brain including Alzheimer's and Parkinson's disease may reveal shared mechanisms for neurodegeneration and potential therapy options.

Diabetic retinopathy (DR) is a challenging public health problem mainly because of its growing prevalence and risk of blindness. In general, our current knowledge and practice have failed to prevent the onset or progression of DR to sight-threatening complications. While there are treatment options for sight-threatening complications of DR, it is crucial to pay more attention to the early stages of DR to decrease its prevalence. Growing evidence suggests many pathologic changes occur before clinical presentations of DR in euglycemic hyperinsulinemia, prediabetes, and diabetes. These pathological changes occur in retinal neurons, glia, and microvasculature. A new focus on these preclinical pathologies - especially on hyperinsulinemia - may provide further insight into disease mechanisms, endpoints for clinical trials, and druggable targets in early disease. Here, we review the current evidence on the pathophysiological changes reported in preclinical DR and appraise preventive and treatment options for DR.

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