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J Proteome Res. 2019 Feb 11. doi: 10.1021/acs.jproteome.8b00915. [Epub ahead of print]

Metabolomic Profiling of Aqueous Humor in Glaucoma Points to Taurine and Spermine Deficiency: Findings from the Eye-D Study.

Author information

1
Département d'Ophtalmologie , Centre Hospitalier Universitaire , Angers 49100 , France.
2
Unité Mixte de Recherche MITOVASC, équipe Mitolab, Centre National de la Recherche Scientifique 6015, Institut National de la Santé et de la Recherche Médicale U1083 , Université d'Angers , Angers 49035 , France.
3
Département de Biochimie et Génétique , Centre Hospitalier Universitaire , Angers 49933 , France.
4
Department of Geriatric Medicine, Angers University Hospital; Angers University Memory Clinic; Research Center on Autonomy and Longevity; UPRES EA 4638 , University of Angers , Angers 49035 , France.
5
Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry , the University of Western Ontario , London , Ontario N6A 3K7 , Canada.
6
Singapore Eye Research Institute , Singapore National Eye Centre , Duke-NUS 168751 , Singapore.

Abstract

We compared the metabolomic profile of aqueous humor from patients with primary open-angle glaucoma (POAG; n = 26) with that of a group of age- and sex-matched non-POAG controls (n = 26), all participants undergoing cataract surgery. Supervised paired partial least-squares discriminant analysis showed good predictive performance for test sets with a median area under the receiver operating characteristic of 0.89 and a p-value of 0.0087. Twenty-three metabolites allowed discrimination between the two groups. Univariate analysis after the Benjamini-Hochberg correction showed significant differences for 13 of these metabolites. The POAG metabolomic signature indicated reduced concentrations of taurine and spermine and increased concentrations of creatinine, carnitine, three short-chain acylcarnitines, 7 amino acids (glutamine, glycine, alanine, leucine, isoleucine, hydroxyl-proline, and acetyl-ornithine), 7 phosphatidylcholines, one lysophosphatidylcholine, and one sphingomyelin. This suggests an alteration of metabolites involved in osmoprotection (taurine and creatinine), neuroprotection (spermine, taurine, and carnitine), amino acid metabolism (7 amino acids and three acylcarnitines), and the remodeling of cell membranes drained by the aqueous humor (hydroxyproline and phospholipids). Five of these metabolic alterations, already reported in POAG plasma, concern spermine, C3 and C4 acylcarnitines, PC aa 34:2, and PC aa 36:4, thus highlighting their importance in the pathogenesis of glaucoma.

KEYWORDS:

aqueous humor; glaucoma; lipidomics; metabolomics; primary open-angle glaucoma

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