The ageing lens

The human lens grows by a process of epithelial cell division at its equato r and the formation of generations of differentiated fibre cells. Despite t he process of continuous remodelling necessary to achieve growth within a c losed system, the lens can retain a high level of light transmission throug hout the lifetime of the individual, with the ability to form sharp images on the retina. Continuous growth of the lens solves the problem imposed by terminal differentiation within a closed, avascular system, from which cell s cannot be shed. The lens fibre tips arch over the equator to meet anterio rly and posteriorly and form branching sutures of increasing complexity. Th e stages of branching may create the optical zones of discontinuity seen on biomicroscopy. The lens is exposed to the cumulative effects of radiation, oxidation and postranslational modification. These later proteins and othe r lens molecules in such a way as to impair membrane functions and perturb protein (particularly crystallin) organisation, so that light transmission and image formation may be compromised. Damage is minimised by the presence of powerful scavenger and chaperone molecules. Progressive insolublisation of the crystallins of the lens nucleus in the first five decades of life, and the formation of higher molecular weight aggregates, may account for th e decreased deformability of the lens nucleus which characterises presbyopi a. Additional factors include: the progressive increase in lens mass with a ge, changes in the point of insertion of the lens zonules, and a shortening of the radius of curvature of the anterior surface of the lens. Also with age, there is a fall in light transmission by the lens, associated with inc reased light scatter, increased spectral absorption, particularly at the bl ue end of the spectrum, and increased lens fluorescence. A major factor res ponsible for the increased yellowing of the lens is the accumulation of a n ovel fluorogen, glutathione-3-hydroxy kynurenine glycoside, which makes a m ajor contribution to the increasing fluorescence of the lens nucleus which occurs with age. Since this compound may also cross-link with the lens crys tallins, it may contribute to the formation of high-molecular-weight aggreg ates and the increases in light scattering which occur with age. Focal chan ges of microscopic size are observed in apparently transparent, aged lenses and may be regarded as precursors of cortical cataract formation. Copyrigh t (C) 2000 S. Karger AG, Basel.