Oxidative Damage and Protective Mechanisms
Free radicals are generated in the course of normal cellular metabolic activities and may also be produced by external agents such as radiant energy. These free radicals, which are highly reactive, can damage lens fibers. Peroxidation of lens fiber plasma or plasma membrane lipids has been suggested as a factor contributing to lens opacification.
Because oxygen tension in and around the lens is normally low, free radical reactions may not involve molecular oxygen; instead, the free radicals may react directly with molecules. DNA is easily damaged by free radicals. Although some of the damage to the lens is reparable, some of it may be permanent. Free radicals can also attack the proteins or membrane lipids in the lens cortex. No repair mechanisms are known to ameliorate such damage. In lens fibers, where protein is no longer synthesized, free radical damage may lead to polymerization and crosslinking of lipids and proteins, resulting in an increase in the water-insoluble protein content.
The lens is equipped with several enzymes that work together to destroy the superoxide anion, O2−, thus protecting against free radical or oxidative damage (Fig 3-4):
Superoxide dismutase catalyzes the destruction of the superoxide anion, O2−.
Catalase breaks down the hydrogen peroxide produced by superoxide dismutase.
Glutathione peroxidase catalyzes a reaction that results in the formation of glutathione disulfide (GSSG), which is then reconverted to glutathione (GSH) by glutathione reductase, using the pyridine nucleotide NADPH. The primary source of erythrocyte NADPH, the HMP shunt provides NADPH as the reducing agent. Thus, glutathione acts indirectly as a major free radical scavenger in the lens.
Figure 3-4 Free radical scavenger pathway in the lens.
(Courtesy of Charles Cole, MD.)
Additionally, both vitamin E and ascorbic acid are present in the lens. Each of these substances can act as a free radical scavenger and thus protect against oxidative damage.
Excerpted from BCSC 2020-2021 series: Section 11 - Lens and Cataract. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.