Glutathione
(GSH) and Eye Health:
Cataracts and Macular Degeneration
Glutathione:
a vital lens antioxidant.
Giblin FJ. [J Ocul Pharmacol Ther. 2000 Apr;16(2):121-35.]
The reducing compound glutathione (GSH) exists in an unusually
high concentration in the lens where it functions as an essential
antioxidant vital for maintenance of the tissue's transparency.
In conjunction with an active glutathione redox cycle located in the
lens epithelium and superficial cortex, GSH detoxifies potentially
damaging oxidants such as H2O2 and dehydroascorbic acid. Recent studies
have indicated an important hydroxyl radical-scavenging function for
GSH in lens epithelial cells, independent of the cells' ability to
detoxify H2O2. Depletion of GSH or inhibition of the redox cycle allows
low levels of oxidant to damage lens epithelial targets such as Na/K-ATPase,
certain cytoskeletal proteins and proteins associated with normal
membrane permeability. The level of GSH in the nucleus of the lens
is relatively low, particularly in the aging lens, and exactly how
the compound travels from the epithelium to the central region of
the organ is not known. Recently, a cortical/nuclear barrier to GSH
migration in older human lenses was demonstrated by Sweeney et al.
The relatively low ratio of GSH to protein -SH in the nucleus of the
lens, combined with low activity of the glutathione redox cycle in
this region, makes the nucleus especially vulnerable to oxidative
stress, as has been demonstrated with use of in vivo experimental
animal models such as hyperbaric oxygen, UVA light and the glutathione
peroxidase knockout mouse. Effects observed in these models, which
are currently being utilized to investigate the mechanism of formation
of human senile nuclear cataract, include an increase in lens nuclear
disulfide, damage to nuclear membranes and an increase in nuclear
light scattering. A need exists for development of therapeutic
agents to slow age-related loss of antioxidant activity in the nucleus
of the human lens to delay the onset of cataract.
Protection
of retinal pigment epithelium from oxidative injury by glutathione
and precursors.
Sternberg P Jr, Davidson PC, Jones DP, Hagen TM, Reed RL, Drews-Botsch
C. [Invest Ophthalmol Vis Sci. 1993 Dec;34(13):3661-8.]
This study was performed to examine the effect of exogenous glutathione
(GSH) or its precursor amino acids on oxidative injury in cultured
human retinal pigment epithelium (RPE). Added GSH provided protection
at concentrations of 0.01 mM and higher. The amino acid precursors
for GSH, glutamate, cysteine, and glycine also protected against injury,
but this required at least 0.1 mM of each amino acid. These
results indicate that protection by the amino acid precursors is mediated
through synthesis of GSH, and they also show that exogenous GSH can
provide protection against oxidative injury.
Glutathione
in human plasma: Decline in association with aging, age- related macular
degeneration, and diabetes
Samiec
PS, Drews-Botsch C, and others. [Free Radic Biol Med 1998 Mar
15;24(5):699-704.] Blood samples were analyzed for GSH and GSH redox
state in 40 age-related macular degeneration (ARMD) patients (>
60 y), 33 non-ARMD diabetic patients (> 60 years), 27 similarly
aged non-ARMD and nondiabetic individuals (> 60 years), and 19
younger individuals (< 60 years) without ARMD or diabetes. Results
showed a significantly lower plasma GSH in older individuals (ARMD,
diabetes, and controls) than in younger individuals. The results suggest
that in studies of age-related pathologies, oxidation of GSH may be
a more important parameter than a decline in pool size, while in specific
pathologies such as diabetes, both oxidation and a decline in pool
size may be important.
Publication
Types:
Clinical Trial
Controlled Clinical Trial
Glutathione
peroxidase-1 deficiency leads to increased nuclear light scattering,
membrane damage, and cataract formation in gene-knockout mice.
Reddy VN, Giblin FJ, Lin LR, Dang L, Unakar NJ, Musch DC, Boyle
DL, Takemoto LJ, Ho YS, Knoernschild T, Juenemann A, Lutjen-Drecoll
E. [Invest Ophthalmol Vis Sci. 2001 Dec;42(13):3247-55.] Previous
in vitro studies with transgenic and gene-knockout mice have shown
that lenses with elevated levels of glutathione peroxidase (GPX)-1
activity are able to resist the cytotoxic effect of H(2)O(2), compared
with normal lenses and lenses from GPX-1-deficient animals. The purpose
of this study was to investigate the functional role of this enzyme
in antioxidant mechanisms of lens in vivo by comparing lens changes
of gene-knockout mice with age-matched control animals. The
results demonstrate the critical role of GPX-1 in antioxidant defense
mechanisms of the lens nucleus.
Specialized
protective role of mucosal glutathione in pigmented rabbit conjunctiva.
Gukasyan HJ, Kim KJ, Kannan R, Farley RA, Lee VH. [Invest
Ophthalmol Vis Sci. 2003 Oct;44(10):4427-38.] To investigate mechanisms
of H(2)O(2)-induced reduction in rates of active ion transport (I(sc))
across the pigmented rabbit conjunctival tissue and the protective
role afforded by mucosal glutathione (GSH). ...actively secreted GSH
by conjunctival epithelial cells may help reduce the injury by mucosally
applied H(2)O(2). Injury by H(2)O(2) may directly affect vital membrane
components (e.g., Na(+),K(+)-ATPase) involved in active ion transport
across conjunctiva. Mucosal protection by GSH (or its analogues)
of active conjunctival ion transport may be useful in maintaining
the physiological functions of conjunctiva under oxidative stress.
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