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

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          Graphical 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.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00216-021-03467-5.

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          Most cited references51

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          Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons.

          To compare the number of retinal ganglion cells (RGCs) topographically mapped with specific visual field threshold test data in the same eyes among glaucoma patients. Seventeen eyes of 13 persons with well-documented glaucoma histories and Humphrey threshold visual field tests (San Leandro, CA) were obtained from eye banks. RGC number was estimated by histologic counts of retinal sections and by counts of remaining axons in the optic nerves. The locations of the retinal samples corresponded to specific test points in the visual field. The data for glaucoma patients were compared with 17 eyes of 17 persons who were group matched for age, had no ocular history, and had normal eyes by histologic examination. The mean RGC loss for the entire retina averaged 10.2%, indicating that many eyes had early glaucoma damage. RGC body loss averaged 35.7% in eyes with corrected pattern SD probability less than 0.5%. When upper to lower retina RGC counts were compared with their corresponding visual field data within each eye, a 5-dB loss in sensitivity was associated with 25% RGC loss. For individual points that were abnormal at a probability less than 0.5%, the mean RGC loss was 29%. In control eyes, the loss of RGCs with age was estimated as 7205 cells per year in persons between 55 and 95 years of age. In optic nerves from glaucoma subjects, smaller axons were significantly more likely to be present than larger axons (R2 = 0.78, P<0.001). At least 25% to 35% RGC loss is associated with statistical abnormalities in automated visual field testing. In addition, these data corroborate previous findings that RGCs with larger diameter axons preferentially die in glaucoma.
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            Exfoliation Syndrome

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              Changes in aqueous humor dynamics with age and glaucoma.

              Changes in aqueous humor dynamics with age and in glaucoma have been studied for several decades. More recently, techniques have been developed which confirm earlier studies showing that outflow facility decreases with age and in glaucoma and add the newer finding that uveoscleral outflow also decreases. Morphologic studies in aging and glaucoma eyes have shown an increase in accumulation of extracellular material in both the trabecular meshwork and ciliary muscle and a loss of trabecular meshwork cells, which contribute to this reduction in outflow and result in an increase in intraocular pressure. A reduction in hyaluronic acid and increases in fibronectin and thrombospondin contribute to the change in the extracellular environment. Imbalances in responses to age-related stresses such as oxidative damage to long-lived molecules, protein cross-linking and loss of elasticity could trigger excess production of factors such as transforming growth factor beta, interleukin-1 and CD44S that could stimulate pathways leading to increases in fibronectin, transformation of trabecular meshwork cells to a myoepithelial state and decrease the breakdown in extracellular matrix material, allowing excess to accumulate. Ultimately trabecular outflow and uveoscleral outflow are reduced and intraocular pressure becomes elevated, adding more stress and perpetuating the pathological condition. Future research to identify additional factors and clarify their roles in these processes could lead to alternative therapies for age and glaucoma related changes in the eye.
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                Author and article information

                Contributors
                Marta.CostasRodriguez@ugent.be
                lobolara@uniovi.es
                Journal
                Anal Bioanal Chem
                Anal Bioanal Chem
                Analytical and Bioanalytical Chemistry
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1618-2642
                1618-2650
                25 June 2021
                25 June 2021
                2022
                : 414
                : 1
                : 515-524
                Affiliations
                [1 ]GRID grid.10863.3c, ISNI 0000 0001 2164 6351, Department of Physical and Analytical Chemistry, , University of Oviedo, ; Avda. Julián Clavería 8, 33006 Oviedo, Spain
                [2 ]GRID grid.5342.0, ISNI 0000 0001 2069 7798, Department of Chemistry, Atomic & Mass Spectrometry – A&MS Research Unit, , Ghent University, ; Campus Sterre, Krijgslaan 281 - S12, 9000 Ghent, Belgium
                [3 ]Instituto Oftalmológico Fernández-Vega, Avda. Fernández-Vega 34, 33012 Oviedo, Spain
                [4 ]GRID grid.10863.3c, ISNI 0000 0001 2164 6351, Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, , Universidad de Oviedo, ; Avda. Fernández-Vega 34, 33012 Oviedo, Spain
                Article
                3467
                10.1007/s00216-021-03467-5
                8748375
                34173037
                6436777c-4f95-4cd1-8ed1-7e0dcc9bba86
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 March 2021
                : 4 May 2021
                : 9 June 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003130, Fonds Wetenschappelijk Onderzoek;
                Award ID: ZW15-02 – G0H6216N
                Funded by: Agencia Estatal de Investigación (Spain) and FEDER
                Award ID: project CTQ2016-79015-R
                Funded by: M. A. thanks University of Oviedo her predoctoral Grant
                Award ID: “Plan de Apoyo y Promoción de la investigació
                Funded by: Instituto de Desarrollo Económico del Principado de Asturias of Gobierno del Principado de Asturias
                Award ID: project IDE/2019/000289
                Funded by: H.G.I. acknowledges the “Cátedra Rafael del Pino
                Categories
                Research Paper
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2022

                Analytical chemistry
                elemental concentration,isotopic composition,inductively coupled plasma–mass spectrometry,aqueous humor,pseudoexfoliation glaucoma

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