Neurodegeneration in the Pathogenesis of Diabetic Retinopathy: Molecular Mechanisms and Therapeutic Implications
Maxwell S. Stem and Thomas W. Gardner
Affiliation: University of Michigan, W. K. Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105, USA.
Diabetic retinopathy (DR), commonly classified as a microvascular complication of diabetes, is now recognized
as a neurovascular complication or sensory neuropathy resulting from disruption of the neurovascular unit. Current
therapies for DR target the vascular complication of the disease process, including neovascularization and diabetic macular
edema. Since neurodegeneration is an early event in the pathogenesis of DR, it will be important to unravel the mechanisms
that contribute to neuroretinal cell death in order to develop novel treatments for the early stages of DR. In this review
we comment on how inflammation, the metabolic derangements associated with diabetes, loss of neuroprotective
factors, and dysregulated glutamate metabolism may contribute to retinal neurodegeneration during diabetes. Promising
potential therapies based on these specific aspects of DR pathophysiology are also discussed. Finally, we stress the importance
of developing and validating new markers of visual function that can be used to shorten the duration of clinical trials
and accelerate the delivery of novel treatments for DR to the public.
Keywords: Diabetes, diabetic retinopathy, mechanisms, neurodegeneration, neurovascular, pathogenesis, treatment.
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