The Carnitine Shuttle Pathway is Altered in Patients With Neovascular Age-Related Macular Degeneration.

Autor:	Mitchell SL; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Uppal K; Department of Medicine, Emory University Medical Center, Atlanta, Georgia, United States., Williamson SM; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Liu K; Department of Medicine, Emory University Medical Center, Atlanta, Georgia, United States., Burgess LG; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Tran V; Department of Medicine, Emory University Medical Center, Atlanta, Georgia, United States., Umfress AC; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Jarrell KL; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Cooke Bailey JN; Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States., Agarwal A; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Pericak-Vance M; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States., Haines JL; Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States., Scott WK; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States., Jones DP; Department of Medicine, Emory University Medical Center, Atlanta, Georgia, United States., Brantley MA Jr; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2018 Oct 01; Vol. 59 (12), pp. 4978-4985.
DOI:	10.1167/iovs.18-25137
Abstrakt:	Purpose: To identify metabolites and metabolic pathways altered in neovascular age-related macular degeneration (NVAMD). Methods: We performed metabolomics analysis using high-resolution C18 liquid chromatography-mass spectrometry on plasma samples from 100 NVAMD patients and 192 controls. Data for mass/charge ratio ranging from 85 to 850 were captured, and metabolic features were extracted using xMSanalyzer. Nested feature selection was used to identify metabolites that discriminated between NVAMD patients and controls. Pathway analysis was performed with Mummichog 2.0. Hierarchical clustering was used to examine the relationship between the discriminating metabolites and NVAMD patients and controls. Results: Of the 10,917 metabolic features analyzed, a set of 159 was identified that distinguished NVAMD patients from controls (area under the curve of 0.83). Of these features, 39 were annotated with confidence and included multiple carnitine metabolites. Pathway analysis revealed that the carnitine shuttle pathway was significantly altered in NVAMD patients (P = 0.0001). Tandem mass spectrometry confirmed the molecular identity of five carnitine shuttle pathway acylcarnitine intermediates that were increased in NVAMD patients. Hierarchical cluster analysis revealed that 51% of the NVAMD patients had similar metabolic profiles, whereas the remaining 49% displayed greater variability in their metabolic profiles. Conclusions: Multiple long-chain acylcarnitines that are part of the carnitine shuttle pathway were significantly increased in NVAMD patients compared to controls, suggesting that fatty acid metabolism may be involved in NVAMD pathophysiology. Cluster analysis suggested that clinically indistinguishable NVAMD patients can be separated into distinct subgroups based on metabolic profiles.
Databáze:	MEDLINE
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