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. Graphical abstract

Neuroprotective Effects of Transferrin in Experimental Glaucoma Models

“…Iron levels were increased in the tears of glaucomatous patients [ 37 ]. However, whilst low iron levels were observed in aqueous humor from pseudo-exfoliating glaucoma (PEXG) patients [ 38 ] and high levels in POAG [ 39 , 40 ], in one recent study, no difference between PEXG or POAG patients compared to control was reported [ 41 ]. Saturation of transferrin and measurement of other iron-regulating proteins might be more relevant than the sole measurement of iron to better identify iron homeostasis deregulation.…”

The Pathomechanism, Antioxidant Biomarkers, and Treatment of Oxidative Stress-Related Eye Diseases

“…If the assumption is true, it will be unsurprising that other studies have shown SOD1/2 and GST1 to be downregulated in the aqueous humor of open-angled glaucoma patients [176]. One study also found Zn levels to be significantly lower in the aqueous humor of glaucoma patients than those of paired controls [174]. In the same study, magnesium was found to be elevated in open-angled glaucoma patients but not in patients with other subtypes of glaucoma.…”

“…However, the change in TAC in the aqueous humor of glaucoma patients is unclear [171]. For example, a study in 2013 showed that TAC in the aqueous humor is decreased in glaucoma patients [170], while another study in 2021 showed an increased outcome [174]. The 2013 study proposed that high oxidative stress was a result of lowered TAC in glaucoma, while the 2021 study hypothesized that high TAC was a reaction to the increased oxidative stress in glaucoma.…”

Microsampling of biological fluids for elemental and isotopic analysis by ICP-MS: strategies and applications for disease diagnosis

“…Aqueous humour helps to maintain intraocular pressure and structural integrity of the ocular globe, provides substrates and removes metabolites from the cornea, lens and trabecular meshwork, and participates in immune and antioxidant responses. 107 Vitreous humour is a gel-like substance that fills the space between the lens and the retina, providing the round shape of the eye and also contributes to vision clarity.…”