Title:Mitochondria Damage in the Pathogenesis of Diabetic Retinopathy and in the Metabolic Memory Associated with its Continued Progression
Volume: 20
Issue: 26
Author(s): Renu A. Kowluru
Affiliation:
Keywords:
Diabetic retinopathy, epigenetic modifications, mitochondria damage, mitochondria DNA, oxidative stress.
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.
