Oxidative damage and the prevention of age-related cataracts

Abstract

Purpose: Cataracts are often considered to be an unavoidable consequence of aging. Oxidative damage is a major cause or consequence of cortical and nuclear cataracts, the most common types of age-related cataracts.

Methods: In this review, we consider the different risk factors, natural history and etiology of each of the 3 major types of age-related cataract, as well as the potential sources of oxidative injury to the lens and the mechanisms that protect against these insults. The evidence linking different oxidative stresses to the different types of cataracts is critically evaluated.

Results: We conclude from this analysis that the evidence for a causal role of oxidation is strong for nuclear, but substantially lower for cortical and posterior subcapsular cataracts. The preponderance of evidence suggests that exposure to increased levels of molecular oxygen accelerates the age-related opacification of the lens nucleus, leading to nuclear cataract. Factors in the eye that maintain low oxygen partial pressure around the lens are, therefore, important in protecting the lens from nuclear cataract.

Conclusions: Maintaining or restoring the low oxygen partial pressure around that lens should decrease or prevent nuclear cataracts.

Fig. 1

Diagrams illustrating the 3 main types of age-related cataracts. a Nuclear cataract. A cross-sectional view of the lens is on the left. It shows the location of a nuclear opacity in the central fiber cells. The pattern of fiber cells is illustrated on the right side of this diagram. The right-hand panel in a shows a view of the lens, as seen through the maximally dilated pupil. The dotted circle shows the approximate location of the pupil during maximal constriction. The cataract is in the center of the visual axis. b Cortical cataract. An opacity in a cluster of cortical fiber cells is illustrated in cross-section on the left and as seen through the pupil on the right. Note that cortical opacities are not visually significant until the opacity reaches the visual axis. c PSC. A cluster of cells has accumulated at the posterior pole of the lens. The opacity is located in the visual axis, where it causes maximal degradation of visual acuity.

Fig. 2

Diagrams illustrating the distribution of oxygen in the normal eye and following vitrectomy or advanced vitreous degeneration. a An eye with an intact vitreous gel. Oxygen diffuses into the vitreous gel from the large retinal vessels. The curved arrows show that much of this oxygen is subsequently consumed by the adjacent retina. The result is a ‘standing gradient’ of oxygen near the retina and relatively low oxygen in the midvitreous and near the lens. The lowest oxygen partial pressure is in the midvitreous, due to the consumption of oxygen by the high concentration of ascorbic acid in the intact vitreous. b An eye with advanced vitreous degeneration (posterior vitreous detachment) or after vitrectomy. The posterior of the globe is filled with liquid, instead of gel. This fluid circulates when the eye moves or as a result of convection, as illustrated by the black, curved arrows. When oxygen is carried away from the retina, it can no longer be consumed by retinal metabolism. The increased mixing of oxygen with the ocular fluids delivers more oxygen to the lens (short arrow), where it leads to nuclear opacification.