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

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.