A direct correlation between the levels of ascorbic acid and H2O2 in aqueous humor

Giblin, Frank J.; McCready, Janet P.; Kodama, Takao; Reddy, Venkat N.

doi:10.1016/0014-4835(84)90142-8

Cited by 126 publications

(36 citation statements)

References 18 publications

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“…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. The presence of ascorbate provides a direct source of hydrogen peroxide with a direct relationship existing between the two [12,13]. A constant source of hydrogen per oxide is therefore available within the anterior chamber of most species, regardless of any ad ditional peroxide generated by free radical me tabolism of oxygen or any other free radical species generated by photochemical reactions or from inflammatory processes.…”

Section: Generalmentioning

confidence: 99%

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

Green

1995

Ophthalmic Res

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A hypothesis is proposed that aging processes in the eye occur as a consequence of degradation of enzymes that normally metabolize and detoxify hydrogen peroxide and other free radicals. The loss of enzyme activity allows hydrogen peroxide, which normally occurs within eye fluids, and free radicals to induce irreversible deleterious effects on different eye tissues. These processes may lead to cataract formation in the lens, loss of corneal endothelial cells, modification of the glycosaminoglycan secretory patterns of the cells of the trabecular meshwork, and other changes associated with ocular aging. These processes may be exacerbated during inflammation when oxidation products increase. Considerable circumstantial evidence points towards hydrogen peroxide as one of the major chemicals involved in the induction of these changes. Much remains to be determined to definitively identify this chemical or free radicals as the primary inducers of tissue alterations that occur in aging eyes.

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Section: Generalmentioning

confidence: 99%

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

Green

1995

Ophthalmic Res

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“…H 2 O 2 in the lens (100 -300 M) has been detected using different methods (5,6). In addition, H 2 O 2 was detected in the aqueous humor (the fluid from which the lens receives its nutriture) of normal (0.03 mM) or cataract patients (0.08 -0.19 mM) by various laboratories (7)(8)(9). Oxidation-induced damage to lens epithelial cells includes bulk protein oxidation, inactivation of some key enzymes, DNA breaks, and lipid peroxidation (3, 10 -14).…”

mentioning

confidence: 99%

Activity of Ubiquitin-dependent Pathway in Response to Oxidative Stress

Shang

Gong

Taylor

1997

Journal of Biological Chemistry

215

135

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Relations between the ubiquitin pathway and cellular stress have been noted, but data regarding responses of the ubiquitin pathway to oxidative stress are scanty. This paper documents the response of this pathway to oxidative stress in lens cells. A brief exposure of lens epithelial cells to physiologically relevant levels of H 2 O 2 induces a transient increase in activity of the ubiquitindependent pathway. Ubiquitin conjugation activity was maximal and increased 3.5-9.2-fold over the activity noted in untreated cells by 4 h after removal of H 2 O 2 . By 24 h after removal of H 2 O 2 , ubiquitin conjugation activity returned to the level noted in untreated cells. In parallel to the changes in ubiquitin conjugation activity, the activity of ubiquitin-activating enzyme (E1), as determined by thiol ester formation, increased 2-6.7-fold during recovery from oxidation. Addition of exogenous E1 resulted in an increase in ubiquitin conjugation activity and in the levels of ubiquitin carrier protein (E2)-ubiquitin thiol esters in both the untreated cells and the H 2 O 2 -treated cells. These data suggest that E1 is the rate-limiting enzyme in the ubiquitin conjugation process and that the increases in ubiquitin conjugation activity which are induced upon recovery from oxidation are primarily due to increased E1 activity. The oxidation-and recovery-induced up-regulation of E1 activity is primarily due to post-synthetic events. Substrate availability and up-regulation of E2 activities also appear to be related to the enhancement in ubiquitinylation upon recovery from oxidative stress. The oxidationinduced increases in ubiquitin conjugation activity were associated with an increase in intracellular proteolysis, suggesting that the transient increase in ubiquitinylation noted upon recovery from oxidative stress may play a role in removal of damaged proteins from the cells.

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“…This was just above the 30-40 ÌM hydrogen peroxide that has been found in normal rabbit aqueous humor [31]. The physiological level of H 2 O 2 in aqueous humor was about the same for all species investigated; in bovine humor it was found to be 25 B 2 ÌM, in primates 27 B 24 ÌM and in human aqueous humor 24 B 7 ÌM [32].…”

Section: Discussionmentioning

confidence: 61%

Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress

Andersson

Sjöstrand²,

Petersen³

et al. 1998

Ophthalmic Res

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The purpose of this study was to examine changes in calcium-dependent proteolytic activity in the lens epithelium from whole rabbit lenses exposed to long-term oxidative stress at near physiological levels. Rabbit lenses, incubated in 50 µM H₂O₂ for 1 or 24 h, were checked for clarity and morphological changes in the epithelium. Proteolytic activity was measured in the epithelium using a fluorogenic synthetic substrate; N-succinyl-Leu-Tyr-7-amino-4-methylcoumarin, both in the presence and the absence of calcium (1 mM Ca²⁺ and 5 mM EDTA respectively). The effect on transparency and morphology of the epithelium following a 1-hour incubation in 100 µM H₂O₂ was also studied. Lenses incubated in 50 µM H₂O₂ were clear even after 24 h. After a 1-hour incubation in 50 µM H₂O₂ the epithelium of the exposed lens appeared normal. However, after 24 h the epithelium cells appeared swollen and microscopical examination showed extensive intracellular and subepithelial vacuolization. Incubation in 100 µM H₂O₂ for 1 h caused loss of transparency; vacuole formation, globulization of the superficial lens fibers and death of the epithelial cells. There was a 55% increase in calcium-dependent proteolytic activity after 1 h in 50 µM H₂O₂, implying a role for the calcium-activated protease calpain in oxidatively induced cataract.

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A direct correlation between the levels of ascorbic acid and H2O2 in aqueous humor

Cited by 126 publications

References 18 publications

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

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

Activity of Ubiquitin-dependent Pathway in Response to Oxidative Stress

Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress

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