Dysregulated metabolic pathways in age-related macular degeneration

Age-related macular degeneration is a major cause of vision impairment in the Western world among people of 55 years and older. Recently we have shown that autophagy is dysfunctional in the retinal pigment epithelium (RPE) of the AMD donor eyes (AMD RPE). We also showed increased reactive oxygen (RO...

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Autores principales: Zhang, Meng, Jiang, Nisi, Chu, Yi, Postnikova, Olga, Varghese, Rency, Horvath, Anelia, Cheema, Amrita K., Golestaneh, Nady
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016007/
https://www.ncbi.nlm.nih.gov/pubmed/32051464
http://dx.doi.org/10.1038/s41598-020-59244-4
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author Zhang, Meng
Jiang, Nisi
Chu, Yi
Postnikova, Olga
Varghese, Rency
Horvath, Anelia
Cheema, Amrita K.
Golestaneh, Nady
author_facet Zhang, Meng
Jiang, Nisi
Chu, Yi
Postnikova, Olga
Varghese, Rency
Horvath, Anelia
Cheema, Amrita K.
Golestaneh, Nady
author_sort Zhang, Meng
collection PubMed
description Age-related macular degeneration is a major cause of vision impairment in the Western world among people of 55 years and older. Recently we have shown that autophagy is dysfunctional in the retinal pigment epithelium (RPE) of the AMD donor eyes (AMD RPE). We also showed increased reactive oxygen (ROS) production, increased cytoplasmic glycogen accumulation, mitochondrial dysfunction and disintegration, and enlarged and annular LAMP-1-positive organelles in AMD RPE. However, the underlying mechanisms inducing these abnormalities remain to be elucidated. Here, by performing a comprehensive study, we show increased PAPR2 expression, deceased NAD+, and SIRT1, increased PGC-1α acetylation (inactive form), lower AMPK activity, and overactive mTOR pathway in AMD RPE as compared to normal RPE. Metabolomics and lipidomics revealed dysregulated metabolites in AMD RPE as compared to normal RPE, including glycerophospholipid metabolism, involved in autophagy, lipid, and protein metabolisms, glutathione, guanosine, and L-glutamic acid, which are implicated in protection against oxidative stress and neurotoxicity, further supporting our observations. Our data show dysregulated metabolic pathways as important contributors to AMD pathophysiology, and facilitate the development of new treatment strategies for this debilitating disease of the visual system.
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spelling pubmed-70160072020-02-21 Dysregulated metabolic pathways in age-related macular degeneration Zhang, Meng Jiang, Nisi Chu, Yi Postnikova, Olga Varghese, Rency Horvath, Anelia Cheema, Amrita K. Golestaneh, Nady Sci Rep Article Age-related macular degeneration is a major cause of vision impairment in the Western world among people of 55 years and older. Recently we have shown that autophagy is dysfunctional in the retinal pigment epithelium (RPE) of the AMD donor eyes (AMD RPE). We also showed increased reactive oxygen (ROS) production, increased cytoplasmic glycogen accumulation, mitochondrial dysfunction and disintegration, and enlarged and annular LAMP-1-positive organelles in AMD RPE. However, the underlying mechanisms inducing these abnormalities remain to be elucidated. Here, by performing a comprehensive study, we show increased PAPR2 expression, deceased NAD+, and SIRT1, increased PGC-1α acetylation (inactive form), lower AMPK activity, and overactive mTOR pathway in AMD RPE as compared to normal RPE. Metabolomics and lipidomics revealed dysregulated metabolites in AMD RPE as compared to normal RPE, including glycerophospholipid metabolism, involved in autophagy, lipid, and protein metabolisms, glutathione, guanosine, and L-glutamic acid, which are implicated in protection against oxidative stress and neurotoxicity, further supporting our observations. Our data show dysregulated metabolic pathways as important contributors to AMD pathophysiology, and facilitate the development of new treatment strategies for this debilitating disease of the visual system. Nature Publishing Group UK 2020-02-12 /pmc/articles/PMC7016007/ /pubmed/32051464 http://dx.doi.org/10.1038/s41598-020-59244-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Meng
Jiang, Nisi
Chu, Yi
Postnikova, Olga
Varghese, Rency
Horvath, Anelia
Cheema, Amrita K.
Golestaneh, Nady
Dysregulated metabolic pathways in age-related macular degeneration
title Dysregulated metabolic pathways in age-related macular degeneration
title_full Dysregulated metabolic pathways in age-related macular degeneration
title_fullStr Dysregulated metabolic pathways in age-related macular degeneration
title_full_unstemmed Dysregulated metabolic pathways in age-related macular degeneration
title_short Dysregulated metabolic pathways in age-related macular degeneration
title_sort dysregulated metabolic pathways in age-related macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016007/
https://www.ncbi.nlm.nih.gov/pubmed/32051464
http://dx.doi.org/10.1038/s41598-020-59244-4
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