Covalent modifications of eye lens proteins by oxidation and glycation

Abstract

The normal mammalian eye lens is a transparent body made up of long newlineenucleated fiber-shaped· cells of epithelial origin which, during differentiation, rid newlinethemselves of large organelles that are likely to scatter light, and overexpress structural newlineproteins called the crystallins to very high intracellular concentrations [200 - 500 newlinemg/ml]. These highly concentrated crystallin solutions achieve a minimization of lightscattering newlinethrough a short-range ordering of molecules into a glass-like state. A newlinereduction in light-scattering is also achieved through a neat inter-cellular stacking of the newlinehexagonally cross-sectioned fiber cells. Thus, the lens owes its transparency, as well newlineas its other optical properties (such as the existence of a smooth radial refractive newlinegradient), to the ordered organization of its constituents. newlineChanges in such molecular ordering, arising from protein conformational newlinecharrges, aggregation and precipitation, bring about an increase in light-scattering newlinethrough both direct scattering of light from particulate protein matter, as well as newlinethrough scattering effected by discontinuities generated in the radial refractive newlinegradient. Such changes tend to be permanent, on account of the fact that lens cells newlinedegrade their nuclei early in development and cannot, therefore, tum over their newlinemolecules. With increase in age, the transmission of light by the lens decreases, newlineespecially at the lower wavelengths. This decrease in transmission is reflected in the newlineincreasing opacity of the lens, in a condition known as cataract. There are several newlinecausal factors for the onset of cataract, primary among these being the processes of newlineoxidation and glycation. newlineWith aging and chronic oxidative stress, crystallins undergo covalent chemical newlinemodifications leading to formation of high molecular weight aggregates, insoluble newlineiv newlineprotein particles and increased pigmentation.