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Author Notes:

Milam A. Brantley, Jr., milam.brantley@vumv.org

Conceptualization: M.A.B.J. and D.P.J.; sample ascertainment: J.L.H., M.A.P.-V., W.K.S. and A.A.; data analysis: C.M. and K.U.; data interpretation: S.L.M., K.U. and M.A.B.J.; writing—original draft preparation: S.L.M., C.M. and K.U.; writing—review and editing: S.L.M., K.U., M.A.B.J., W.K.S. and A.A. All authors have read and agreed to the published version of the manuscript.

The authors thank all the patients who generously participated in this study. The authors acknowledge Jessica N. Cooke Bailey for extracting data from the database, and ViLinh Tran and Yating Wang for their technical expertise with the mass spectrometer.

No conflicting relationships exist for any of the authors.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • age-related macular degeneration
  • IAMD
  • NVAMD
  • metabolomics
  • acylcarnitines
  • carnitine shuttle
  • phospholipids
  • HIGH-RESOLUTION METABOLOMICS
  • MASS-SPECTROMETRY
  • N-ACYLETHANOLAMINE
  • WIDE ASSOCIATION
  • CHROMATOGRAPHY
  • MODEL

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

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Journal Title:

CELLS

Volume:

Volume 10, Number 11

Publisher:

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2021 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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