Clocking in on Diabetic Retinopathy

  1. Jayakrishna Ambati1,2
  1. 1Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky
  2. 2Department of Physiology, University of Kentucky, Lexington, Kentucky
  1. Corresponding author: Jayakrishna Ambati, jamba2{at}email.uky.edu.

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the U.S. and has created a massive health care burden. Chronic hyperglycemia leads to specific changes in the retina, including the loss of pericytes, basement membrane thickening, and impaired endothelial cell function. However, the biological explanation of these cellular events remains unclear. Eventually, these changes lead to the formation of microaneurysms, the breakdown of the tight junctions in the retinal vasculature, subsequent extravasation of fluid, and vision loss. DR often progresses to a more deleterious proliferative phenotype due to profound ischemia with neovascularization of the retina and vitreous hemorrhage. Given this substantial clinical problem, many researchers are focused on resolving molecular mechanisms in DR pathogenesis to identify potential new therapeutic targets. Although a significant cache of data has amassed in studies linking DR to proinflammatory mediators such as vascular endothelial growth factor-A, oxidative stress, and abnormal glycosylation, there is growing excitement over the recent discovery linking circadian dysfunction and diabetes and the implications of this biology in the eye.

The central mammalian clock located in the suprachiasmatic nucleus is sensitive to disturbances in the programmed 24-h circadian cycle controlled by the oscillatory expression of a clock gene cassette including Period (Per) 13, Cryptochrome (Cry) 1/2, Clock, and Bmal1/2. As the retina provides a critical signal entry point for …

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