Dysregulated metabolic pathways in age-related macular degeneration

Autor:	Rency S. Varghese, Nady Golestaneh, Anelia Horvath, Yi Chu, Nisi Jiang, Olga A. Postnikova, Meng Zhang, Amrita K. Cheema
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Male medicine.medical_specialty genetic structures lcsh:Medicine Retinal Pigment Epithelium medicine.disease_cause Article Macular Degeneration AMP-Activated Protein Kinase Kinases Sirtuin 1 Internal medicine Metabolome Metabolomics Humans Medicine lcsh:Science PI3K/AKT/mTOR pathway Multidisciplinary Retinal pigment epithelium business.industry Autophagy lcsh:R Neurotoxicity Lipid metabolism Macular degeneration Lipid Metabolism medicine.disease Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha eye diseases Mitochondria Mechanisms of disease Endocrinology medicine.anatomical_structure Female lcsh:Q sense organs Poly(ADP-ribose) Polymerases Reactive Oxygen Species Transcriptome business Protein Kinases Glycogen Metabolic Networks and Pathways Oxidative stress
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) Scientific Reports
ISSN:	2045-2322
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d95c9c63d263e5067e330f86ffc3ca04 http://link.springer.com/article/10.1038/s41598-020-59244-4 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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