Quantitative detection of the molecular changes associated with early cataractogenesis in the living human lens using quasielastic light scattering

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Abstract
We have used quasielastic light scattering to detect and quantitatively characterize the molecular changes associated with the early stages of cataractogenesis in the living human lens. The autocorrelation function of the fluctuations in the light scattered by the lens shows the presence of two major species responsible for the scattering. The first, fast diffusing species (f), has a diffusivity of .apprx. 3 .times. 10-7 cm2/sec and corresponds to the alpha crystallin proteins. The second, slow diffusing species (s), has a diffusivity of .apprx. 10-9 cm2/sec and corresponds to the diffusivity of a large aggregate. The intensity of light If and Is scattered into the collection optics by each of these species was also measured. We studied a group of 49 individuals ranging in age from 21 years to 82 years. In this group 40 presented with preoperative cataract development. In this patient population we found that regardless of age, or position in the lens that a plot of Itot = If + Is versus Is could be well fitted by a straight line with a slope less than unity and a positive intercept Ifo. It has been possible to explain this finding using a two state model for the molecular changes associated with early cataractogenesis. In this model the proteins in the slow diffusing species are aggregates each containing a definite number of rapidly diffusing proteins. The early development of cataract is represented by the redistribution of protein between the unaggregated form (f) and the aggregated form (s). The prediction for the relationship between Itot and Is based on this two state model is in very good agreement with our experimental data. Indeed the measured position of the point (Itot, Is) along this line provides a sensitive, and quantitative measure of the degree of cataract development at any selected location in the lens.