Mitochondria Damage in the Pathogenesis of Diabetic Retinopathy and in the Metabolic Memory Associated with its Continued Progression
Abstract:Diabetic retinopathy is the leading cause of blindness in young adults, and with the incidence of diabetes increasing at a frightening rate, retinopathy is estimated to threaten vision for almost 51 million patients worldwide. In diabetes, mitochondria structure, function and DNA (mtDNA) are damaged in the retina and its vasculature, and the mtDNA repair machinery and biogenesis are compromised. Proteins encoded by mtDNA become subnormal contributing to dysfunctional electron transport system, and the transport of proteins that are important in mtDNA biogenesis and function, but are encoded by nuclear DNA, is impaired. These diabetes-induced abnormalities in mitochondria continue even when hyperglycemic insult is terminated, and are implicated in the metabolic memory phenomenon associated with the continued progression of diabetic retinopathy. Diabetes also facilitates epigenetic modifications-the changes in histones and DNA methylation in response to cells changing environmental stimuli, which the cell can memorize and pass to the next generation. Epigenetic modifications contribute to the mitochondria damage, and are postulated in the development of diabetic retinopathy, and also to the metabolic memory phenomenon. Thus, strategies targeting mitochondria homeostasis and/or enzymes important for histone and DNA methylation could serve as potential therapies to halt the development and progression of diabetic retinopathy.
Document Type: Research Article
Publication date: 2013-09-01
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