A metabolomics profiling of glaucoma points to mitochondrial dysfunction, senescence, and polyamines deficiency

Abstract

PURPOSE. To determine the plasma metabolomic signature of primary open-angle glaucoma (POAG). METHODS. We compared the metabolomic profiles of plasma from individuals with POAG (n = 36) with age-and sex-matched controls with cataract (n = 27). A targeted metabolomics study was performed using the standardized p180 Biocrates Absolute IDQ p180 kit with a QTRAP 5500 mass spectrometer. Multivariate analyses were performed using principal component analysis (PCA) and the least absolute shrinkage and selection operator (LASSO) method. RESULTS. Among the 151 metabolites accurately measured, combined univariate and multivariate analyses revealed 18 discriminant metabolites belonging to the carbohydrate, acyl-carnitine, phosphatidylcholine, amino acids, and polyamine families. The metabolomic signature of POAG points to three closely interdependent pathophysiologic conditions; that is, defective mitochondrial oxidation of energetic substrates, altered metabolism resembling that observed in senescence, and a deficiency in spermidine and spermine, both polyamines being involved in the protection of retinal ganglion cells. CONCLUSIONS. Our results highlight a systemic and age-related mitochondrial defect in the pathogenesis of POAG.