Metabolic profiles associated with primary open-angle glaucoma

Abstract

Purpose: To determine if primary open-angle glaucoma (POAG) patients can be differentiated from controls based on metabolic characteristics.

Methods: We performed metabolomic analysis using C18 liquid chromatography-Fourier-transform mass spectrometry on frozen plasma samples from 72 POAG patients and 72 controls. Data were collected from mass/charge ratio (m/z) 85-2000 on a Thermo LTQ-Velos Orbitrap mass spectrometer. Metabolic features were extracted with xMSanalyzer and filtered using log2 fold change in order to isolate 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 POAG.

Results: After data filtering, 2440 m/z features were recovered from the 144 plasma samples. Forty-one features were significantly different between POAG patients and controls using FDR (q=0.05). These discriminating features included palmitoyl carnitine and sphingosine metabolites, each previously linked to glaucoma. Pathway analysis of the 41 m/z features and their correlated features revealed galactose metabolism, fructose and mannose metabolism, and steroid hormone biosynthesis pathways to be associated with disease status.

Conclusions: Metabolomics can identify both individual metabolites and metabolic pathways that discriminate POAG cases from controls. These results suggest palmitoyl carnitine and sphingosine metabolites, as well as carbohydrate metabolism and steroid hormone biosynthesis pathways, to be involved in POAG pathophysiology.

Keywords: 464 clinical (human) or epidemiologic studies: risk factor assessment • 592 metabolism