No 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.

Oxygen metabolism by the lens and cornea establishes oxygen gradients in the anterior segment. Vitrectomy and cataract surgery increase pO(2) in the anterior chamber angle, potentially damaging trabecular meshwork cells. We propose that oxygen levels in the anterior chamber angle are strongly influenced by oxygen derived from the ciliary body circulation.

Intraocular oxygen is mostly derived from the retinal and iris vasculature and by diffusion across the cornea. Freshly secreted aqueous humor and the aqueous humor in the anterior chamber angle are relatively depleted of oxygen. The marked increase in oxygen consumption that occurs when the lens is exposed to increased oxygen is likely to result in the production of higher levels of reactive oxygen species and may provide a link between elevated oxygen levels and the risk of nuclear cataracts.

Loss of vitreous gel during aging increases the risk of nuclear cataracts. Preservation or replacement of the vitreous gel may protect patients from nuclear cataract.

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Collagen, hyaluronan, and proteoglycans act synergistically to maintain vitreous stiffness. Hyaluronan is a key mediator of vitreous adhesivity, and mechanical damping is an important factor influencing dynamic vitreous behavior.

BetaB1- and gammaS-crystallins are normally abundant in adult mammalian lens epithelial cells. Complex programs of transcription and degradation regulate the accumulation of crystallin mRNAs in lens epithelial cells after stress, at different ages, and during cell differentiation. Because crystallins selectively localize in distinct subcellular compartments during differentiation or stress, they may function to protect lens cells from injury. After stress, most alphaA- and alphaB-crystallin subunits are not in the same macromolecular complexes.