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

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 leastsquares 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.

Multi-Omics Approach for Studying Tears in Treatment-Naïve Glaucoma Patients

“…Some other studies reported the metabolomics of the aqueous humor in a rat model of POAG using nuclear magnetic resonance [20]. The last investigation described metabolomic profiling of aqueous humor in POAG patients by a standardized targeted metabolomics strategy [18]. Thus, to our knowledge, the present study, is the first that investigates the metabolic profiling of tears in naïve to therapy glaucomatous patients, even if only a small cohort of tear samples were analyzed.…”

“…Considering the global incidence of POAG and the great impact of an early stage disease diagnosis on the patient quality of life, screening strategies for early diagnosis and treatment of POAG are highly required [16]. To date, only few studies described the metabolomic profiles in POAG using mass spectrometry [15,17,18]. Many of these studies have been performed on the blood of individuals with POAG.…”

Neuroinflammation in Primary Open-Angle Glaucoma

“…Moreover, also the levels of hydroxyproline, derived from the hydrolysis of collagen [ 93 ] and acetate [ 94 ], the latter correlating with the changes in outflow dynamics, due to either cell loss or the dysfunction of sub-cellular structures, increase in POAG AH.…”

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma

“…It has been suggested that taurine supplementation may have a neuroprotective effect in retina [ 199 ]. Accordingly, taurine improved RGC survival in a rat retinal explant exposed to serum deprivation or N-methyl-D-aspartate (NMDA) [ 200 ].…”