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Glutathione and Eye Disease

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Cataract

A Cataract [1-5] is an opacification of the lens and is the major cause of blindness worldwide. The WHO estimates around 20 million people have bilateral blindness from cataract.  As longevity increases, the impact of cataracts on society is also expected to increase [6].

A major risk factor in cataract is exposure to sunlight.  Although not yet fully understood, the cause is likely the ionizing UV radiation spectrum of sunlight. This ionizing radiation promotes the production of free radicals in the lens leading to oxidative stress which is a key factor in cataract formation [5].   Interestingly, an unusually high level of glutathione (GSH) is found in the lens which plays a vital role in maintaining lens transparency by quenching free radicals.

Cataract surgery is currently the main treatment approach; however, it is very costly and often associated with complications. It can reasonably be expected that by maintaining an optimal concentration of glutathione in the lens, cataract formation can be inhibited, especially as we age.  Supplementation with gamma-glutamylcysteine is key here.

Macular degeneration

Macular degeneration is an eye disease that causes permanent vision loss. It is triggered by damage to the nerves in the eye resulting in blurred vision as well as loss of vision in the center of the field of vision. It is a major concern in the elderly and is prevalent in most developed countries.

Oxidative stress in the retinal pigment epithelium in the macular of the eye has been hypothesized to be a major driving force in the progression of this disease [7].   A decrease in glutathione  associated with ageing and diabetes has been correlated with age-related macular degeneration [8]. 

Preliminary invitro studies have shown that N-acetylcysteine derivatives showed some protection of retinal pigment epithelium cells to oxidative attack [7].  It is expected that by maintaining an optimal concentration of glutathione in the macular by supplementation with gamma-glutamylcysteine, macular degeneration can be inhibited, especially as we age.  

References

1.            Giblin, F.J., Glutathione: a vital lens antioxidant. Journal of Ocular Pharmacology & Therapeutics, 2000. 16(2): p. 121-35

2.            Lou, M.F., Redox regulation in the lens. Progress in Retinal and Eye Research, 2003. 22(5): p. 657-682

3.            Beebe, D.C. and Y.-B. Shui, Progress in Preventing Age-Related Cataract, in Ocular Therapeutics, Y. Thomas, F.C. Abbot, and B.W. Martin, Editors. 2008, Academic Press: London. p. 143-165.

4.            Shoham, A., M. Hadziahmetovic, J.L. Dunaief, M.B. Mydlarski, and H.M. Schipper, Oxidative stress in diseases of the human cornea. Free Radical Biology and Medicine, 2008. 45(8): p. 1047-1055

5.            Ho, M.-C., Y.-J. Peng, S.-J. Chen, and S.-H. Chiou, Senile cataracts and oxidative stress. Journal of Clinical Gerontology and Geriatrics, 2010. 1(1): p. 17-21

6.            Beebe, D.C., Y.-B. Shui, and N.M. Holekamp, Biochemical mechanisms of age-related cataract, in Ocular Disease, A.L. Leonard, et al., Editors. 2010, W.B. Saunders: Edinburgh. p. 231-237.

7.            Kularatne, R.N., C. Bulumulla, T. Catchpole, A. Takacs, A. Christie, M.C. Stefan, and K.G. Csaky, Protection of human retinal pigment epithelial cells from oxidative damage using cysteine prodrugs. Free Radical Biology and Medicine, 2020. 152: p. 386-394

8.            Samiec, P.S., C. Drews-Botsch, E.W. Flagg, J.C. Kurtz, P. Sternberg, R.L. Reed, and D.P. Jones, Glutathione in Human Plasma: Decline in Association with Aging, Age-Related Macular Degeneration, and Diabetes. Free Radical Biology and Medicine, 1998. 24(5): p. 699-704

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