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Decreased total antioxidants status in the plasma of patients with pseudoexfoliation glaucoma.

ABSTRACT: PURPOSE: To evaluate total antioxidant status (TAS) in the plasma of pseudoexfoliation glaucoma (PEG) patients and to compare this level with a matching control group. Additionally, we aim to investigate the effect of the combined action of the lysyl oxidase-like 1 (LOXL1) mutation status with TAS level on the development of PEG. METHODS: Plasma samples were obtained from 54 PEG patients and 54 controls of matching age, sex, and ethnicity. TAS in all samples was determined by spectrophotometric and enzyme-linked immunosorbent assay methods. The coding region of LOXL1, where it encompasses both single nucleotide polymorphisms (SNPs; rs1048661 and rs3825942), was sequenced. RESULTS: The mean (±SD) total antioxidant (TAS) value was lower among patients: 0.87 (0.24), range 0.9-1.41 than controls: 1.07 (0.23), range 0.72-1.94, and this difference was statistically significant (p<0.0001: 95%CI: -0.295-0.114). Evaluating the impact of age, sex, and the mutation in addition to the mean TAS value in patients with PEG, a logistic regression analysis was conducted using diseased/not diseased as the outcome of interest (the dependent variable). Results show that, controlling for all other variables, mean TAS value (p<0.0001) and the mutation G/G in rs3825942 (p=0.041) are significant risk factors for PEG. CONCLUSIONS: Our findings provide evidence that TAS decreases in the plasma of PEG patients, suggesting that TAS may have an important role in the pathogenesis of PEG. The combined effect of the "G" allele and the decreased TAS may contribute to the overall pathogenesis of PEG.

SUBMITTER: Abu-Amero KK

PROVIDER: S-EPMC3209429 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Decreased total antioxidants status in the plasma of patients with pseudoexfoliation glaucoma.

Abu-Amero Khaled K KK Kondkar Altaf A AA Mousa Ahmed A Osman Essam A EA Al-Obeidan Saleh A SA

Molecular vision 20111025

<h4>Purpose</h4>To evaluate total antioxidant status (TAS) in the plasma of pseudoexfoliation glaucoma (PEG) patients and to compare this level with a matching control group. Additionally, we aim to investigate the effect of the combined action of the lysyl oxidase-like 1 (LOXL1) mutation status with TAS level on the development of PEG.<h4>Methods</h4>Plasma samples were obtained from 54 PEG patients and 54 controls of matching age, sex, and ethnicity. TAS in all samples was determined by spectr ...[more]

PMID: 22065931

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Project description:PurposeTo investigate systemic oxidative stress-induced DNA damage in patients with pseudoexfoliation glaucoma (PXG), we estimated plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker for oxidative DNA damage in comparison to controls. In addition, we also examined a combined effect of lysyl oxidase-like 1 (LOXL1) polymorphism status and 8-OHdG levels on PXG risk.Materials and methodsA retrospective case-control study was performed to estimate plasma levels of 8-OHdG in 41 PXG patients and 45 nonglaucomatous controls using the enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicate on an automated ELISA analyzer. Two common polymorphisms (rs1048661 and rs3835942) in LOXL1 gene were genotyped by Sanger sequencing.ResultsThe mean and median levels of 8-OHdG were significantly increased in the PXG cases (p=0.032) and male subjects (p=0.041). Subjects with levels greater than the third quartile (75% percentile) exhibited a significant increased risk of PXG (odds ratio = 4.06, 95% confidence interval (CI = 1.11-14.80, p=0.029)). Within- and between-group comparisons showed that the mean levels were higher in individuals carrying the LOXL1 risk variant (G/G), but not statistically significant. In logistic regression analysis, both 8-OHdG (p=0.044) and rs3835942 (p=0.012) showed a statistically significant effect on the PXG outcome. However, the effect was lost when age, sex, and rs1048661 were included. A significant positive correlation was observed between 8-OHdG levels and intraocular pressure (R=0.284, p=0.008) and cup/disc ratio (R=0.233, p=0.031). Furthermore, in receiver operating characteristic analysis, the area under the curve was statistically significant (p=0.032) with a value of 0.635 (95% CI = 0.518-0.751).ConclusionThe study demonstrates an association of increased plasma levels of 8-OHdG in patients with PXG, supporting the role of oxidative stress, and increased oxidative DNA damage in PXG development.

Project description:Pseudoexfoliation (PEX) syndrome, one of the most common causes of glaucoma, represents a complex, multifactorial, late-onset disease of worldwide significance. The etiopathogenesis involves both genetic and non-genetic factors. The PEX-specific tissue alterations are caused by a generalized fibrotic matrix process, which has been characterized as a stress-induced elastosis associated with the excessive production and abnormal cross-linking of elastic microfibrils into fibrillar PEX aggregates. The identification of lysyl oxidase-like 1 (LOXL1) as a major genetic risk factor for PEX syndrome and PEX glaucoma further supports a role of elastogenesis and elastosis in the pathophysiology of PEX, as LOXL1 is a pivotal cross-linking enzyme in elastic fiber formation and stabilization. The available data suggest that LOXL1 is markedly dysregulated depending on the stage of the fibrotic process. While transient upregulation of LOXL1 during the early stages of PEX fibrogenesis participates in the formation and aggregation of abnormal PEX fiber deposits, the decreased expression of LOXL1 during the advanced stages of the disease may affect elastin metabolism and promote elastotic processes, e.g. in the lamina cribrosa, predisposing to glaucoma development. However, in view of the low penetrance of the PEX-associated risk variants of LOXL1, other genetic and/or environmental factors must contribute to the risk of developing the PEX phenotype. Some evidence exists for the contribution of additional genes with relatively small effects, e.g. clusterin (CLU), contactin-associated protein-like 2 (CNTNAP2), apolipoprotein E (APOE), glutathione S-transferases (GSTs), and tumor necrosis factor-alpha (TNFA), in certain study populations. Several environmental conditions associated with PEX, such as oxidative stress as well as pro-fibrotic cytokines and growth factors, can regulate expression of LOXL1 and elastic proteins in vitro and may therefore act as co-modulating external factors. Ultimately, both detection and functional characterization of yet unidentified genetic and non-genetic factors may lead to the development of more precise screening tools for the risk of PEX glaucoma.

Dataset Information

Decreased total antioxidants status in the plasma of patients with pseudoexfoliation glaucoma.

Publications

Decreased total antioxidants status in the plasma of patients with pseudoexfoliation glaucoma.

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