Roles of Catalase and the Glutathione Redox Cycle in the Regulation of Anterior-Chamber Hydrogen Peroxide

Abstract

The effects of inhibition of both glutathione synthesis and of glutathione reductase and catalase activities have been determined in the regulation of hydrogen peroxide (H₂O₂) in the anterior chamber of pigmented rabbits. Glutathione reductase inhibition using intravitreal 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) did not significantly alter either total glutathione or the percent oxidized glutathione fraction in the iris-ciliary body. Intravitreal buthionine sulfoximine (BSO) significantly reduced the total glutathione content of iris-ciliary body and corneal endothelium, while not altering the oxidized fraction. BCNU increased the oxidized fraction of glutathione in the aqueous humor from 22 to 63% without significantly altering total glutathione levels. BSO, however, reduced total glutathione by 70% in the aqueous humor, and the oxidized fraction doubled. Decreases in the reduced glutathione concentration caused by BSO correlate with increases in the normally stable ratio of H₂O₂ to ascorbate concentrations in the aqueous humor, strongly suggesting that glutathione metabolism is correlated with H₂O₂ regulation at endogenous levels of this oxidant. Both BSO and 3-aminotriazole (3AT) separately increased the half-time for the loss of exogenously added H₂0₂ from the anterior chamber. BSO increased the half-time by 77% after 10 μl of 10 mMH₂O₂ was injected intracamerally, while suppression of catalase activity with 3AT increased it by only 40%. With intracameral injections of 10 μl of either 25 or 50 mM H₂O₂, however, 3AT had a greater effect than BSO. The half-time values after 3AT pretreat-ment were 61 and 135% greater than control values at the concentrations of 25 and 50 mM H₂O₂, respectively; those after BSO pretreatment were at 14 and 78%. From these data we conclude that the glutathione redox system protects the anterior segment tissues from hydrogen peroxide at low concentrations of this oxidant, while catalase assumes a greater role at higher concentrations of hydrogen peroxide.

Free Radicals and Aging of Anterior Segment Tissues of the Eye: A Hypothesis

“…Such phenomena have been the subject of experimental approaches, differing in quantitiy and emphasis for each tissue of the eye, and a common theme appears present. Of importance is the fact that hydrogen peroxide has been found to occur in the aqueous humor at concen trations of up to 50 [iM [7][8][9][10][11], Thus, one of the primary requirements for the hypothesis has been proven, namely that at least one of the products of the metabolism of free radicals ex ists in the fluids bathing the tissues of interest. The situation in the anterior chamber for the presence of hydrogen peroxide is facilitated by the presence in the majority of mammalian spe cies of an elevated ascorbic acid concentration generated by an active transport system in the ciliary epithelium.…”

Glaucoma in Patients with Parkinson’s Disease

“…Currently, there is only one study pointing on an increased rate of glaucoma in patients with PD (23.7%), mostly normal tension glaucoma [8]. An increased risk of glaucoma in course of PD may be a result of decreased level of reduced glutathione (GSH), one of the prominent antioxidants found in the eye [9,10]. GSH protects ocular tissue from damage caused by oxidative stress, which is implicated in the pathogenesis of primary open angle glaucoma, especially with normal IOP [11].…”

The Role of Retinal Oxidative and Nitrative Injury in Glaucomatous Neurodegeneration

“…Hydrogen peroxide formed in the anterior segment tissues of the eye is removed by the heme-containing enzyme catalase or by glutathione peroxidase (Costarides et al, 1991). The specific activity of superoxide dismutase and catalase can be measured in both normal fresh human cadaver trabecular meshwork (De La Paz & Epstein, 1996) and in the iris and corneal endothelium of rabbits (Riley, 1990).…”