Increase of Water-Insoluble Proteins With Age
As the lens ages, its proteins aggregate, forming very large particles. These particles become water-insoluble and scatter light, increasing the opacity of the lens. Even if the lens remains relatively transparent, the water-insoluble protein fraction increases with age. Although conversion of the water-soluble proteins into water-insoluble proteins appears to be a natural process in lens fiber maturation, it may occur more quickly in cataractous lenses.
In cataracts with significant browning of the lens nucleus (brunescent cataracts), the increase in the amount of water-insoluble protein is directly correlated to the degree of opacification. In markedly brunescent cataracts, up to 90% of the nuclear proteins may be insoluble. Associated oxidative changes, including protein-to-protein and protein-to-glutathione disulfide bond formation, result in decreased levels of the reduced form of glutathione and increased levels of glutathione disulfide (oxidized glutathione) in the cytoplasm of the nuclear fiber cells. Glutathione is generally considered essential to maintain a reducing environment in the lens cytoplasm. Depletion of the reduced form of glutathione accelerates protein crosslinking, protein aggregation, and light scattering.
In addition to the increased formation of disulfide bonds, nuclear proteins are highly crosslinked by nondisulfide bonds. This insoluble protein fraction contains yellow-to-brown pigments that are found in higher concentration in nuclear cataracts. Increased fluorescence is generated by the nondisulfide crosslinks that form in brunescent nuclear cataracts.
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.