The ageing lens and cataract: a model of normal and pathological ageing

Abstract

Cataract is a visible opacity in the lens substance, which, when located on the visual axis, leads to visual loss. Age-related cataract is a cause of blindness on a global scale involving genetic and environmental influences. With ageing, lens proteins undergo non-enzymatic, post-translational modification and the accumulation of fluorescent chromophores, increasing susceptibility to oxidation and cross-linking and increased light-scatter. Because the human lens grows throughout life, the lens core is exposed for a longer period to such influences and the risk of oxidative damage increases in the fourth decade when a barrier to the transport of glutathione forms around the lens nucleus. Consequently, as the lens ages, its transparency falls and the nucleus becomes more rigid, resisting the change in shape necessary for accommodation. This is the basis of presbyopia. In some individuals, the steady accumulation of chromophores and complex, insoluble crystallin aggregates in the lens nucleus leads to the formation of a brown nuclear cataract. The process is homogeneous and the affected lens fibres retain their gross morphology. Cortical opacities are due to changes in membrane permeability and enzyme function and shear-stress damage to lens fibres with continued accommodative effort. Unlike nuclear cataract, progression is intermittent, stepwise and non-uniform.

Biophysical chemistry of the ageing eye lens

“…However, one of the most interesting and well-studied eye components in regards to ageing is the lens, opacification of which leads to impaired vision which characterises cataract disease. (Augusteyn 2010;Banh et al 2006;Bloemendal et al 2004;Michael and Bron 2011).…”

“…2). The outward facing edge of the lens consists of a mono-layer of epithelial cells contacting the iris, from which new fibre cells develop as the lens grows over the lifetime of the individual (Banh et al 2006;Michael and Bron 2011). The lens epithelial cells are the only part of the lens that has metabolic activity (Dahm et al 2011).…”

“…In general, this opacity can either result from a disruption in the ordered packing of the lens fibre cells or from the formation of large structures within the cells due to a disruption in local ordered protein structure (Michael and Bron 2011;Moreau and King 2012). In the latter case, this disruption is often caused by the formation of high molecular weight structures consisting of aggregated crystallin proteins (Dobson 2004).…”

“…Such structures exhibit increased light scattering, which reduces lens transparency and eventually causes loss of vision. Age-related nuclear cataract is a common disease of ageing and is highly correlated with fibre cell crystallin protein aggregation (Bloemendal et al 2004;Harding 2002;Michael and Bron 2011;Petrash 2013).…”

“…While the lens has systems to prevent protein aggregation (Ecroyd and Carver 2009;Horwitz 2003), the build-up of damaging modifications over time will eventually overwhelm them and aggregate formation results. Cataract has become an inevitable reality of ageing, especially as the lifetimes of individuals increases (Michael and Bron 2011). Currently, the only effective treatment for cataract-related blindness is surgical removal of the clouded lens and replacement with a prosthesis (Rao et al 2011).…”