April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Metabolic pathways altered in neovascular age-related macular degeneration
Author Affiliations & Notes
  • Milam A Brantley
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, TN
  • Karan Uppal
    Department of Medicine, Emory University, Atlanta, GA
  • Samantha L Williamson
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, TN
  • L. Goodwin Burgess
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, TN
  • Anita Agarwal
    Vanderbilt Eye Institute, Vanderbilt University, Nashville, TN
  • Margaret A Pericak-Vance
    Hussman Institute of Human Genomics, Miller School of Medicine, University of Miami, Miami, FL
  • Jonathan Haines
    Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH
  • Dean P Jones
    Department of Medicine, Emory University, Atlanta, GA
  • Footnotes
    Commercial Relationships Milam Brantley, None; Karan Uppal, None; Samantha Williamson, None; L. Goodwin Burgess, None; Anita Agarwal, None; Margaret Pericak-Vance, None; Jonathan Haines, None; Dean Jones, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1650. doi:
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      Milam A Brantley, Karan Uppal, Samantha L Williamson, L. Goodwin Burgess, Anita Agarwal, Margaret A Pericak-Vance, Jonathan Haines, Dean P Jones; Metabolic pathways altered in neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1650.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To identify metabolic pathways that are altered in neovascular age-related macular degeneration (NVAMD).

Methods: We performed metabolomic analysis using C18 liquid chromatography-Fourier transform mass spectrometry (LC-FTMS) on frozen plasma samples from 60 NVAMD patients and 117 controls. Data were collected from mass/charge ratio (m/z) 85-2000 on a Thermo LTQ-Velos Orbitrap mass spectrometer, and metabolic features were extracted using an adaptive processing software package with xMSanalyzer. Log2 fold change filtering and the Limma package in R were used to identify differentially expressed metabolites (DEMs). P-values were corrected using Benjamini and Hochberg False Discovery Rate (FDR) to account for multiple testing. Metabolome-wide Spearman correlation was performed for the DEMs to identify top correlated features. DEMs and top correlated features were matched to the Metlin metabolomics database and further analyzed with MetaboAnalyst to identify metabolic pathways most significantly altered in NVAMD.

Results: After data filtering, 8563 m/z features were analyzed. A total of 101 m/z features were found to significantly differ between NVAMD cases and controls using FDR q=0.1. Pathway analysis with MetaboAnalyst showed the primary bile acid biosynthesis pathway to be significantly altered in NVAMD (p=4.73 x 10-12), with approximately seven times the number of expected hits seen for this pathway. Many of these hits were putatively matched to molecules in the sterol biosynthesis pathway, the initial phase of primary bile acid synthesis.

Conclusions: Metabolomic analysis can be used to identify individual metabolites that discriminate NVAMD cases from controls, and subsequent pathway analysis can identify the metabolic pathways that are most altered in disease. The results indicating the involvement of bile acid metabolism correspond with findings in our previous study of an independent case-control cohort and also advance current knowledge by isolating primary bile acid biosynthesis as affecting NVAMD status.

Keywords: 412 age-related macular degeneration • 592 metabolism  
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