Systemic Reduction in Glutathione Levels Occurs in Patients with Primary Open-Angle Glaucoma

Gherghel, Doina; Griffiths, Helen R.; Hilton, E J Roff; Cunliffe, I A; Hosking, Sarah

doi:10.1167/iovs.04-0777

Cited by 164 publications

(129 citation statements)

References 68 publications

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“…38 For example, the reduction in glutathione, a major antioxidant in the retina, was reported in the plasma of human glaucoma patients. 39 A similar reduction in glutathione concentration and increased oxidative stress were detected in GLAST KO mice. 6 We previously reported that apoptosis signal-regulating kinase 1 (ASK1), a member of mitogen-activated protein 3 kinase, is involved in RGC loss in GLAST KO mice.…”

Section: Discussionmentioning

confidence: 65%

Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma

et al. 2013

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Dedicator of cytokinesis 3 (Dock3), a new member of the guanine nucleotide exchange factors for the small GTPase Rac1, promotes axon regeneration following optic nerve injury. In the present study, we found that Dock3 directly binds to the intracellular C-terminus domain of NR2B, an N-methyl-D-aspartate (NMDA) receptor subunit. In transgenic mice overexpressing Dock3 (Dock3 Tg), NR2B expression in the retina was significantly decreased and NMDA-induced retinal degeneration was ameliorated. In addition, overexpression of Dock3 protected retinal ganglion cells (RGCs) from oxidative stress. We previously reported that glutamate/aspartate transporter (GLAST) is a major glutamate transporter in the retina, and RGC degeneration due to glutamate neurotoxicity and oxidative stress is observed in GLAST-deficient (KO) mice. In GLAST KO mice, the NR2B phosphorylation rate in the retina was significantly higher compared with Dock3 Tg:GLAST KO mice. Consistently, glaucomatous retinal degeneration was significantly improved in GLAST KO:Dock3 Tg mice compared with GLAST KO mice. These results suggest that Dock3 overexpression prevents glaucomatous retinal degeneration by suppressing both NR2B-mediated glutamate neurotoxicity and oxidative stress, and identifies Dock3 signaling as a potential therapeutic target for both neuroprotection and axonal regeneration.

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Section: Discussionmentioning

confidence: 65%

Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma

et al. 2013

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“…Gherghel et al, for example, reported that glaucoma patients exhibit low levels of circulating glutathione, suggesting compromised oxidative defence. 22 Ferreira et al reported a significant decrease in total reactive antioxidant potential and increased superoxide dismutase and glutathione peroxidase activity in the aqueous humor from patients with glaucoma. 23 Sorkhabi et al reported that oxidative DNA damage increases and total antioxidant status decreases in the serum and aqueous humor of glaucoma patients.…”

Section: Introductionmentioning

confidence: 98%

Black Currant Anthocyanins Normalized Abnormal Levels of Serum Concentrations of Endothelin-1 in Patients with Glaucoma

Yoshida

Ohguro

2013

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Our recent study, which involved a randomized, placebo-controlled, double-masked 24-month trial (Ophthalmologica 2012;228:26-35), revealed that oral administration of black currant anthocyanins (BCACs) slowed down the visual field deterioration and elevation of ocular blood flow of open-angle glaucoma (OAG). To elucidate the underlying mechanisms of these BCAC-induced effects, as possible factors affecting glaucomatous optic neuropathy, changes of serum endothelin-1 (ET-1), nitric oxide (NO), and antioxidative activities were examined in the present study. Methods: From among patients with OAG who participated in the randomized, placebo-controlled, doublemasked trial, serum specimens were obtained from BCAC-treated (n = 19) or placebo-treated (n = 19) patients at baseline and every 6 months. Healthy volunteers (n = 20) with age and gender matching the patients were used as a control. Serum ET-1 concentration, [NO 2 -] and [NO 2 -+ NO 3 -] levels, advanced oxidation protein products (AOPP), and antioxidant activities were measured by using commercially available kits. Results: At the trial baseline, serum ET-1 concentrations were significantly lower in patients with OAG (BCACs, 3.18 -1.06 pg/mL; placebo, 3.44 -0.84 pg/mL) than those in healthy volunteers (4.38 -1.03 pg/mL) (one-way analysis of variance and a Tukey's multiple comparison post hoc test, P < 0.05). Upon administration of BCACs, serum ET-1 concentrations increased to the levels of those in healthy volunteers during the 24-month period. In contrast, those of placebo-treated patients remained at lower levels (3.82 -1.14 pg/mL). While [NO 2 -] and [NO 2 -+ NO 3 -] levels, AOPP, and antioxidative activities of patients from both the BCACs and placebo groups showed comparable levels to those of healthy subjects at baseline, no significant changes were observed during the observational period in either the BCAC or placebo groups. Conclusions: Among the possible beneficial effects of BCACs toward visual field progression in patients with OAG, our present results suggest that BCACs caused normalization of serum ET-1 levels, and this may modulate ET-1-dependent regulation of the ocular blood hemodynamics.

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“…GSH plays a critical role as an intracellular defense system providing detoxification of a broad spectrum of reactive species and allowing their excretion as watersoluble conjugates (Meister, 1989). Glaucomatous patients exhibit low levels of circulating glutathione (Gherghel et al 2005) and glutathione participates directly in the neutralization of free radicals and reactive oxygen species, and maintains exogenous antioxidants such as vitamins C and E in their reduced (active) forms (Saccà et al 2007). Insufficient glutathione combined with exogenous H 2 O 2 may induce collagen matrix remodeling and TM cell apoptosis independently of mitochondria (Veach 2004).…”

Section: Oxidative Stress and Trabecular Meshworkmentioning

confidence: 99%

Oxidative Stress in Anterior Segment of Primary Open Angle Glaucoma

Saccà¹,

Izzotti²

2011

Glaucoma - Current Clinical and Research Aspects

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Systemic Reduction in Glutathione Levels Occurs in Patients with Primary Open-Angle Glaucoma

Abstract: Patients with glaucoma exhibit low levels of circulating glutathione, suggesting a general compromise of the antioxidative defense.

Cited by 164 publications

References 68 publications

Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma

Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma

Black Currant Anthocyanins Normalized Abnormal Levels of Serum Concentrations of Endothelin-1 in Patients with Glaucoma

Oxidative Stress in Anterior Segment of Primary Open Angle Glaucoma

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