Abstract
Purpose::
To assess the association of Dynamic Light Scattering (DLS) measurements of the lens with aging and with nuclear lens opacity, and to demonstrate that an "Alpha (α)-Crystallin Index" can be calculated, which is a measure of available α-crystallin in a living lens, and which is associated with the susceptibility of a lens to develop cataract.
Methods::
Using a DLS early cataract detection clinical device developed by NASA and the NEI, we performed non invasive DLS measurements on 235 subjects (380 eyes), of both sexes, with ages 7-86 years and with AREDS clinical lens nucleus grades ranging from 0 to 3.8 (on a scale of 0-4, with 4 representing a dense nuclear opacity). All facets of the Declaration of Helsinki were followed. DLS data consist of a bimodal distribution of lens proteins based on size. The first peak consists of smaller particles, primarily composed of the α-crystallin lens protein fraction. α-crystallins have been shown to be the internal molecular chaperone proteins which prevent lens protein aggregation and cataract formation. The second peak consists of higher molecular weight proteins, primarily aggregated lens proteins. An α-Crystallin Index (αCI) was derived from the bimodal data and correlated with subjects’ age and lens grade. The αCI is defined as the proportion of the DLS light-scattering intensity attributable to α-crystallins relative to the total light scattering intensity.
Results::
αCI values ranged from 0 to 41.4%. There was a significant decrease of αCI associated with increasing age (p<0.001) and increasing cataract grades (p<0.001). The mean value of αCI in young (below age 22) clear lenses was 31%, compared with a mean αCI value of 2% in eyes with advanced cataract (grade of 3 or higher). Most older subjects with some cataract (grade 2 or higher) and nearly all eyes with advanced cataract (grade 3 or higher) had an αCI value of 0%. The standard error of measurement (repeatability) of αCI was 3%.
Conclusions::
The αCI, a measure of the amount of clinically measurable alpha-crystallin in the lens, statistically significantly decreases with age and with increasing nuclear opacity. This new objective measure, obtained by Dynamic Light Scattering, appears to be directly associated with the α-crystallin level in the lens in vivo. Decreasing levels of α-crystallin are associated with increased risk of cataract development.
Keywords: cataract • crystallins • clinical (human) or epidemiologic studies: systems/equipment/techniques