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Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease

Diabetic retinopathy (DR), a common chronic complication of diabetes mellitus and the leading cause of vision loss in the working-age population, is clinically defined as a microvascular disease that involves damage of the retinal capillaries with secondary visual impairment. While its clinical diag...

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Autores principales: Miller, David J., Cascio, M. Ariel, Rosca, Mariana G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598160/
https://www.ncbi.nlm.nih.gov/pubmed/32977483
http://dx.doi.org/10.3390/antiox9100905
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author Miller, David J.
Cascio, M. Ariel
Rosca, Mariana G.
author_facet Miller, David J.
Cascio, M. Ariel
Rosca, Mariana G.
author_sort Miller, David J.
collection PubMed
description Diabetic retinopathy (DR), a common chronic complication of diabetes mellitus and the leading cause of vision loss in the working-age population, is clinically defined as a microvascular disease that involves damage of the retinal capillaries with secondary visual impairment. While its clinical diagnosis is based on vascular pathology, DR is associated with early abnormalities in the electroretinogram, indicating alterations of the neural retina and impaired visual signaling. The pathogenesis of DR is complex and likely involves the simultaneous dysregulation of multiple metabolic and signaling pathways through the retinal neurovascular unit. There is evidence that microvascular disease in DR is caused in part by altered energetic metabolism in the neural retina and specifically from signals originating in the photoreceptors. In this review, we discuss the main pathogenic mechanisms that link alterations in neural retina bioenergetics with vascular regression in DR. We focus specifically on the recent developments related to alterations in mitochondrial metabolism including energetic substrate selection, mitochondrial function, oxidation-reduction (redox) imbalance, and oxidative stress, and critically discuss the mechanisms of these changes and their consequences on retinal function. We also acknowledge implications for emerging therapeutic approaches and future research directions to find novel mitochondria-targeted therapeutic strategies to correct bioenergetics in diabetes. We conclude that retinal bioenergetics is affected in the early stages of diabetes with consequences beyond changes in ATP content, and that maintaining mitochondrial integrity may alleviate retinal disease.
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spelling pubmed-75981602020-10-31 Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease Miller, David J. Cascio, M. Ariel Rosca, Mariana G. Antioxidants (Basel) Review Diabetic retinopathy (DR), a common chronic complication of diabetes mellitus and the leading cause of vision loss in the working-age population, is clinically defined as a microvascular disease that involves damage of the retinal capillaries with secondary visual impairment. While its clinical diagnosis is based on vascular pathology, DR is associated with early abnormalities in the electroretinogram, indicating alterations of the neural retina and impaired visual signaling. The pathogenesis of DR is complex and likely involves the simultaneous dysregulation of multiple metabolic and signaling pathways through the retinal neurovascular unit. There is evidence that microvascular disease in DR is caused in part by altered energetic metabolism in the neural retina and specifically from signals originating in the photoreceptors. In this review, we discuss the main pathogenic mechanisms that link alterations in neural retina bioenergetics with vascular regression in DR. We focus specifically on the recent developments related to alterations in mitochondrial metabolism including energetic substrate selection, mitochondrial function, oxidation-reduction (redox) imbalance, and oxidative stress, and critically discuss the mechanisms of these changes and their consequences on retinal function. We also acknowledge implications for emerging therapeutic approaches and future research directions to find novel mitochondria-targeted therapeutic strategies to correct bioenergetics in diabetes. We conclude that retinal bioenergetics is affected in the early stages of diabetes with consequences beyond changes in ATP content, and that maintaining mitochondrial integrity may alleviate retinal disease. MDPI 2020-09-23 /pmc/articles/PMC7598160/ /pubmed/32977483 http://dx.doi.org/10.3390/antiox9100905 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Miller, David J.
Cascio, M. Ariel
Rosca, Mariana G.
Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease
title Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease
title_full Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease
title_fullStr Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease
title_full_unstemmed Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease
title_short Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease
title_sort diabetic retinopathy: the role of mitochondria in the neural retina and microvascular disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598160/
https://www.ncbi.nlm.nih.gov/pubmed/32977483
http://dx.doi.org/10.3390/antiox9100905
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