Abstract
PurposeTo determine if plasma metabolic profiles can detect differences between patients with neovascular age-related macular degeneration (NVAMD) and similarly-aged controls.MethodsMetabolomic analysis using liquid chromatography with Fourier-transform mass spectrometry (LC-FTMS) was performed on plasma samples from 26 NVAMD patients and 19 controls. Data were collected from mass/charge ratio (m/z) 85 to 850 on a Thermo LTQ-FT mass spectrometer, and metabolic features were extracted using an adaptive processing software package. Both non-transformed and log2 transformed data were corrected using Benjamini and Hochberg False Discovery Rate (FDR) to account for multiple testing. Orthogonal Partial Least Squares-Discriminant Analysis was performed to determine metabolic features that distinguished NVAMD patients from controls. Individual m/z features were matched to the Kyoto Encyclopedia of Genes and Genomes database and the Metlin metabolomics database, and metabolic pathways associated with NVAMD were identified using MetScape.ResultsOf the 1680 total m/z features detected by LC-FTMS, 94 unique m/z features were significantly different between NVAMD patients and controls using FDR (q = 0.05). A comparison of these features to those found with log2 transformed data (n = 132, q = 0.2) revealed 40 features in common, reaffirming the involvement of certain metabolites. Such metabolites included di- and tripeptides, covalently modified amino acids, bile acids, and vitamin D-related metabolites. Correlation analysis revealed associations among certain significant features, and pathway analysis demonstrated broader changes in tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to urea metabolism.ConclusionsThese data suggest that metabolomic analysis can identify a panel of individual metabolites that differ between NVAMD cases and controls. Pathway analysis can assess the involvement of certain metabolic pathways, such as tyrosine and urea metabolism, and can provide further insight into the pathophysiology of AMD.
Highlights
Age-related macular degeneration (AMD) remains a leading cause of irreversible vision loss in older individuals in developed countries
Twelve of the 26 Neovascular AMD (NVAMD) patients (46.1%) had active choroidal neovascularization at the time of the blood draw, and 9 (34.6%) patients had received an intravitreal injection of anti-vascular endothelial growth factor (VEGF) within the preceding two months
The results show that the metabolic profiles of NVAMD patients and controls differed in contents of features that varied independently and in content of features that varied with group-wise character
Summary
Age-related macular degeneration (AMD) remains a leading cause of irreversible vision loss in older individuals in developed countries. Neovascular AMD (NVAMD), in which blood or serous fluid leaks from abnormal choroidal or retinal vessels, is responsible for the majority of AMD-related vision loss [2]. Risk of developing this complex disease is influenced by genetic, demographic, and environmental factors. Genetic variants in the complement factor H gene (CFH) and the age-related maculopathy susceptibility 2/HtrA serine peptidase 1 (ARMS2/HTRA1) locus have been strongly and consistently associated with AMD.
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