A Metabolomics Profiling of Glaucoma Points to Mitochondrial Dysfunction, Senescence, and Polyamines Deficiency.
Stéphanie Leruez, Alexandre Marill, Thomas Bresson, Saint Martin Grégoire de, Adrien Buisset, Jeanne Muller, Lydie Tessier, Cédric Gadras, Christophe Verny, Philippe Gohier, Patrizia Amati-Bonneau, Guy Lenaers, Dominique Bonneau, Gilles Simard, Dan Milea, Vincent Procaccio, Pascal Reynier, de la Barca Juan Manuel Chao
Summary
Our results highlight a systemic and age-related mitochondrial defect in the pathogenesis of POAG.
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.
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Discussion
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