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    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    2 Fundamentals and Principles of Ophthalmology

    Part IV: Biochemistry and Metabolism

    Chapter 14: Reactive Oxygen Species and Antioxidants

    Oxidative Damage to the Lens and Protective Mechanisms

    As stated earlier, ROS are generated by metabolic processes, inflammatory responses, and exposure to UV light. The lens relies almost entirely on anaerobic metabolism and is shielded from the immune system. Thus, the major source of ROS in the lens is exposure to UV light. Although most UVB radiation (<320-nm wavelength) striking the human eye is absorbed either by the cornea or by the ascorbate present at high levels in the aqueous humor, a certain amount reaches the lens epithelium, where it can cause damage. UVA light (320–400-nm wavelength) can penetrate more deeply into the lens, where it can react with various chromophores to generate H2O2, O2•−, and 1O2.

    Although repair and regeneration mechanisms are active in the lens epithelium and superficial cortex, no such mechanisms exist in the deep cortex and the nucleus, where any damage to lens proteins and membrane lipids is irreversible. One result of this damage can be crosslinking and insolubilization of proteins, leading to loss of transparency (see Chapter 10 in this volume and BCSC Section 11, Lens and Cataract). The lens contains unusually high levels of protein sulfhydryl groups that must exist almost entirely in the reduced state for the tissue to remain transparent. The young, healthy lens possesses a variety of effective antioxidant systems to protect against oxidative stress. These defenses include the enzymes glutathione reductase, GSH-Px, catalase, and SOD (see Fig 14-1).

    Glutathione (GSH), concentrated at the lens epithelium, acts as a major scavenger of ROS in the lens. With age, levels of GSH decline significantly in the human lens, particularly in the nucleus. Studies have indicated that a cortical–nuclear barrier may exist in the mature human lens, which inhibits the free flow of GSH to the nucleus. As a result, the human lens nucleus becomes more susceptible to oxidative damage and cataract formation with age.

    The free radical scavengers ascorbate and vitamin E, also present in the lens, work in conjunction with GSH and the GSH oxidation-reduction (redox) cycle to protect against oxidative damage (see Fig 14-2). Carotenoids that can quench 1O2 also exist in the lens. Epidemiologic (observational) studies have shown that individuals with higher levels of plasma antioxidants, particularly vitamin E, have a reduced risk of cataract, especially nuclear cataract. However, 3 prospective randomized placebo-controlled clinical trials—Age-Related Eye Disease Study (AREDS); Age-Related Eye Disease Study 2 (AREDS2); and the Vitamin E, Cataract, and Age-Related Maculopathy Trial (VECAT)—found that high-dose formulations of antioxidants neither prevented the development nor slowed the progression of age-related cataracts.

    • Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9. Arch Ophthalmol. 2001;119(10):1439–1452. [Erratum appears in Arch Ophthalmol. 2008;126(9):1251.]

    • Age-Related Eye Disease Study 2 (AREDS2) Research Group; Chew EY, SanGiovanni JP, Ferris FL, et al. Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. JAMA Ophthalmol. 2013;131(7):843–850.

    • Cetinel S, Semenchenko V, Cho JY, et al. UV-B induced fibrillization of crystallin protein mixtures. PLoS One. 2017;12(5):e0177991.

    • McNeil JJ, Robman L, Tikellis G, Sinclair MI, McCarty CA, Taylor HR. Vitamin E supplementation and cataract: randomized controlled trial. Ophthalmology. 2004;111(1):75–84.

    Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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