The long-term objective of this project is to understand how age-related changes in the lens proteins contribute to cataract. The proposed research will examine the composition and structure of light scattering protein aggregates and water-insoluble protein that form in aged human lenses using mass spectrometry. The specific aims of the project are to: 1) quantify the protein composition of protein aggregates and water-insoluble protein in normal and cataractous human lenses; 2) identify sites in aggregated and water-insoluble lens proteins that form intermolecular disulfide cross-links during aging, and 3) map the contact sites occurring in aggregated and water-insoluble lens proteins using chemical cross-linkers. The results will provide new information about the structure of light scattering proteins in human lens so that the mechanism of age-related protein aggregation and insolubilization can be eventually deduced. This information may lead to therapeutic strategies to slow the rate of age-related cataract formation by inhibiting protein aggregation. The research is important to human health, because cataracts are a major human disease for which there is no useful treatment other than surgical extraction of the lens.