Ascorbic Acid Modulation of Iron Homeostasis and Lysosomal Function in Trabecular Meshwork Cells

Xu, Ping; Lin, Yizhi; Porter, Kristine; Liton, Paloma B.

doi:10.1089/jop.2013.0183

Cited by 18 publications

(16 citation statements)

References 39 publications

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“…Even if glaucoma is a multifactorial disease [7,10], systemic oxidative stress may play an important role in the pathophysiology of POAG and PEG. Despite growing research on antioxidant therapy to prevent glaucoma, in both in vitro [64] and in vivo studies with animals [65] and humans [66], antioxidative supplementation has shown contradictory [66,67,68]. However, there were promising results of supplementation in endothelial function [69], some specific clinical conditions [70] and overall mortality [71].…”

Section: Discussionmentioning

confidence: 99%

Oxidative and Anti-Oxidative Stress Markers in Chronic Glaucoma: A Systematic Review and Meta-Analysis

d'Azy¹,

Pereira²,

et al. 2016

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Chronic glaucoma is a multifactorial disease among which oxidative stress may play a major pathophysiological role. We conducted a systematic review and meta-analysis to evaluate the levels of oxidative and antioxidative stress markers in chronic glaucoma compared with a control group. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies reporting oxidative and antioxidative stress markers in chronic glaucoma and in healthy controls using the following keywords: “oxidative stress” or “oxidant stress” or “nitrative stress” or “oxidative damage” or “nitrative damage” or “antioxidative stress” or “antioxidant stress” or “antinitrative stress” and “glaucoma”. We stratified our meta-analysis on the type of biomarkers, the type of glaucoma, and the origin of the sample (serum or aqueous humor). We included 22 case-control studies with a total of 2913 patients: 1614 with glaucoma and 1319 healthy controls. We included 12 studies in the meta-analysis on oxidative stress markers and 19 on antioxidative stress markers. We demonstrated an overall increase in oxidative stress markers in glaucoma (effect size = 1.64; 95%CI 1.20–2.09), ranging from an effect size of 1.29 in serum (95%CI 0.84–1.74) to 2.62 in aqueous humor (95%CI 1.60–3.65). Despite a decrease in antioxidative stress marker in serum (effect size = –0.41; 95%CI –0.72 to –0.11), some increased in aqueous humor (superoxide dismutase, effect size = 3.53; 95%CI 1.20–5.85 and glutathione peroxidase, effect size = 6.60; 95%CI 3.88–9.31). The differences in the serum levels of oxidative stress markers between glaucoma patients and controls were significantly higher in primary open angle glaucoma vs primary angle closed glaucoma (effect size = 12.7; 95%CI 8.78–16.6, P < 0.001), and higher in pseudo-exfoliative glaucoma vs primary angle closed glaucoma (effect size = 12.2; 95%CI 8.96–15.5, P < 0.001). In conclusion, oxidative stress increased in glaucoma, both in serum and aqueous humor. Malonyldialdehyde seemed the best biomarkers of oxidative stress in serum. The increase of some antioxidant markers could be a protective response of the eye against oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Oxidative and Anti-Oxidative Stress Markers in Chronic Glaucoma: A Systematic Review and Meta-Analysis

d'Azy¹,

Pereira²,

et al. 2016

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“…The potential relevance of AA in outflow pathway physiology and pathophysiology comes from the observed IOP-lowering effect of AA (LINNER, 1969), and from the recent work by Zanon-Moreno et al (Zanon-Moreno et al, 2011) reporting an association between a polymorphism in the AA transporter SLC23A2 with lower plasma concentrations of AA and with higher risk of POAG. Very interestingly, supplementation of TM cells with AA has been shown to activate the autophagic lysosomal pathway and increase lysosomal degradation in TM cells in a dose-dependent manner (Xu et al, 2014). This increase in lysosomal degradation was mediated by proteolytic activation of cathepsins, presumably through the stabilization of lysosomal pH, as described in glial cells (Martin et al, 2002).…”

Section: Autophagy In Outflow Pathway Pathophysiology: Implicationmentioning

confidence: 99%

The autophagic lysosomal system in outflow pathway physiology and pathophysiology

Liton

2016

Experimental Eye Research

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Malfunction of the trabecular meshwork (TM)/schlemm’s canal (SC) conventional outflow pathway is associated with elevated intraocular pressure (IOP) and, therefore, increased risk of developing glaucoma, a potentially blinding disease affecting more than 70 million people worldwide. This TM/SC tissue is subjected to different types of stress, including mechanical, oxidative, and phagocytic stress. Long-term exposure to these stresses is believed to lead to a progressive accumulation of damaged cellular and tissue structures causing permanent alterations in the tissue physiology, and contribute to the pathologic increase in aqueous humor (AH) outflow resistance. Autophagy is emerging as an essential cellular survival mechanism against a variety of stressors. In addition to performing basal functions, autophagy acts as a cellular survival pathway and represents an essential mechanism by which organisms can adapt to acute stress conditions and repair stress-induced damage. A decline in autophagy has been observed in most tissues with aging and has been considered responsible, at least in part, for the accumulation of damaged cellular components in almost all tissues of aging organisms. Dysfunction in the autophagy pathway is associated with several human diseases, from infectious diseases to cancer and neurodegeneration. In this review, we will summarize our current knowledge of the emerging roles of autophagy in outflow tissue physiology and pathophysiology, including novel evidence suggesting compromised autophagy in the glaucomatous outflow pathway.

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“…Vitamin C appears to have a particularly important role, in fact within the cell, vitamin C helps to protect membrane lipids from peroxidation by recycling vitamin E. 191 This could be relevant in all eye diseases that we talked about, especially in glaucoma where the Vitamin C has a direct effect on the trabecular meshwork where might improve their ability to degrade proteins within the lysosomal compartment and recover tissue function. 192 Therefore Ascorbic acid supplementation may improve the effectiveness of Hp-eradication therapy. 193 Besides, diets rich in naturally occurring ascorbic acid are associated with protection of the gastric corpus from atrophy and a reduction in the incidence of gastric cancer possibly through the ability of ascorbic acid to reduce oxidative damage to the gastric mucosa by scavenging carcinogenic N -nitroso compounds and free radicals and attenuating the Hp-induced inflammatory cascade.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Infection and Eye Diseases

et al. 2014

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The connection between Helicobacter pylori (Hp) infection and eye diseases has been increasingly reported in the literature and in active research. The implication of this bacterium in chronic eye diseases, such as blepharitis, glaucoma, central serous chorioretinopathy and others, has been hypothesized. Although the mechanisms by which this association occurs are currently unknown, this review describes shared pathogenetic mechanisms in an attempt to identify a lowest common denominator between eye diseases and Hp infection.The aim of this review is to assess whether different studies could be compared and to establish whether or not Hp infection and Eye diseases share common pathogenetic aspects. In particular, it has been focused on oxidative damage as a possible link between these pathologies.Text word search in Medline from 1998 to July 2014.152 studies were included in our review.Were taken into considerations only studies that related eye diseases more frequent and/or known.Likely oxidative stress plays a key role. All of the diseases studied seem to follow a common pattern that implicates a cellular response correlated with a sublethal dose of oxidative stress. These alterations seem to be shared by both Hp infections and ocular diseases and include the following: decline in mitochondrial function, increases in the rate of reactive oxygen species production, accumulation of mitochondrial DNA mutations, increases in the levels of oxidative damage to DNA, proteins and lipids, and decreases in the capacity to degrade oxidatively damaged proteins and other macromolecules. This cascade of events appears to repeat itself in different diseases, regardless of the identity of the affected tissue. The trabecular meshwork, conjunctiva, and retina can each show how oxidative stress may acts as a common disease effector as the Helicobacter infection spreads, supported by the increased oxidative damage and other inflammation.

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Ascorbic Acid Modulation of Iron Homeostasis and Lysosomal Function in Trabecular Meshwork Cells

Cited by 18 publications

References 39 publications

Oxidative and Anti-Oxidative Stress Markers in Chronic Glaucoma: A Systematic Review and Meta-Analysis

Oxidative and Anti-Oxidative Stress Markers in Chronic Glaucoma: A Systematic Review and Meta-Analysis

The autophagic lysosomal system in outflow pathway physiology and pathophysiology

Helicobacter pylori Infection and Eye Diseases

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