Homeostatic alterations related to total antioxidant capacity, elemental concentrations and isotopic compositions in aqueous humor of glaucoma patients

Abstract

Glaucoma is a multifactorial eye disease, characterized by progressive optic neurodegeneration. Elevation of the intraocular pressure is the main risk factor for glaucoma and is a consequence of an imbalance in the aqueous humor hydrodynamics, the physiology of which is influenced by the homeostatic equilibrium of essential elements, oxidative stress, and antioxidants. The aim of this work was to study local alterations in glaucomatous patients from two different, but connected, points of view: (i) the total antioxidant capacity (as an indicator of oxidative damage) and (ii) the concentration of mineral elements and their isotopic composition. Such objective was pursued using aqueous humor from patients diagnosed with pseudoexfoliation glaucoma (PEXG, n = 17) and primary open-angle glaucoma (POAG, n = 5) and age-matched control subjects (n = 16). The total antioxidant capacity (TAC) was examined in both aqueous humor and 60 serum samples (n = 20 controls, n = 20 for PEXG, and n = 20 for POAG), both showing higher TAC for the glaucoma population. The concentrations of the essential mineral elements (Cu, Fe, Mg, Na, P, and Zn) and the isotopic compositions of Cu and Zn were determined in aqueous humor using single-collector and multi-collector inductively coupled plasma-mass spectrometry, respectively. Significant differences were established for Mg and P levels when comparing the results for glaucomatous patients with those for the control population (p < 0.01 and p < 0.05 for Mg and P respectively, ANOVA and Kruskal-Wallis). The Zn isotopic composition was significantly shifted from that for the control population for PEXG patients. A significant difference in the isotopic composition of Zn was also established between the PEXG and POAG glaucoma cohorts.

Keywords: Aqueous humor; Elemental concentration; Inductively coupled plasma–mass spectrometry; Isotopic composition; Pseudoexfoliation glaucoma.

Fig. 1

Box plots for Q1, Q2, and Qt (μC) measured in aqueous humor of patients suffering from pseudoexfoliation glaucoma (n = 14) and of controls (n = 12). n.s., not significant; *p-value <0.05; **p-value <0.01; ***p-value <0.001

Fig. 2

Box plots for Mg, P, and Na (mg L⁻¹) and Fe, Cu, and Zn (μg L⁻¹) comparing aqueous humor concentration levels of patients suffering PEXG (n = 17) and POAG (n = 5) and controls (n = 16). n.s., not significant. *p-value < 0.05; **p-value < 0.01; ***, p-value <0.001

Fig. 3

Box plots for δ⁶⁵Cu (‰) and δ⁶⁶Zn (‰) measured in aqueous humor of patients suffering PEXG (n = 17), of patients suffering from POAG (n = 5), and of controls (n = 16). n.s., not significant. *p-value < 0.05; **p-value < 0.01; ***p-value <0.001