Plasma Metabolomics of Intermediate and Neovascular Age-Related Macular Degeneration Patients

• Type of Material: Article
• Authors: Sabrina L Mitchell, Vanderbilt University; Chunyu Ma, Emory University; William K Scott, Univ Miami Miller; Anita Agarwal, Vanderbilt University; Margaret A Pericak-Vance, University of Miami Miller; Jonathan L Haines, Case Western Reserve University; Dean Jones, Emory University; Karan Uppal, Emory University; Milam A Brantley Jr, Vanderbilt University
• Language: English
• Date: 2021-11-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cells10113141
• Title of Journal or Parent Work: CELLS
• Volume: 10
• Issue: 11
• Grant/Funding Information: This work was supported by National Institutes of Health grants R01 EY22618 (MAB) and R01 EY012118 (MP-V, JLH, WKS, and AA) and an unrestricted award to the Vanderbilt Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness. The sponsor or funding organization had no role in the design or conduct of this research.
• Keywords: carnitine shuttle; CHROMATOGRAPHY; WIDE ASSOCIATION; acylcarnitines; IAMD; NVAMD; Life Sciences & Biomedicine; HIGH-RESOLUTION METABOLOMICS; MODEL; Cell Biology; MASS-SPECTROMETRY; age-related macular degeneration; N-ACYLETHANOLAMINE; metabolomics; Science & Technology; phospholipids
• Research Categories: Health Sciences, Opthamology; Health Sciences, Medicine and Surgery

Abstract

To characterize metabolites and metabolic pathways altered in intermediate and neovascular age-related macular degeneration (IAMD and NVAMD), high resolution untargeted metabolomics was performed via liquid chromatography-mass spectrometry on plasma samples obtained from 91 IAMD patients, 100 NVAMD patients, and 195 controls. Plasma metabolite levels were compared between: AMD patients and controls, IAMD patients and controls, and NVAMD and IAMD patients. Partial least-squares discriminant analysis and linear regression were used to identify discriminatory metabolites. Pathway analysis was performed to determine metabolic pathways altered in AMD. Among the comparisons, we identified 435 unique discriminatory metabolic features. Using computational methods and tandem mass spectrometry, we identified 11 metabolic features whose molecular identities had been previously verified and confirmed the molecular identities of three additional discriminatory features. Included among the discriminatory metabolites were acylcarnitines, phospholipids, amino acids, and steroid metabolites. Pathway analysis revealed that lipid, amino acid, and vitamin metabolism pathways were altered in NVAMD, IAMD, or AMD in general, including the carnitine shuttle pathway which was significantly altered in all comparisons. Finally, few discriminatory features were identified between IAMD patients and controls, suggesting that plasma metabolic profiles of IAMD patients are more similar to controls than to NVAMD patients.