The relatively long half life of lens proteins has been attributed to the low level and tight control of proteolytic activity. During the last few years the accumulation of peptides in senile cataract and every cataract model has been documented. It has been hypothesized that the limited proteolysis of the crystallins by lens proteases and the incomplete removal of the peptides generated may contribute to cataract development. However, in spite of extensive studies on lens proteolytic system, breakdown of the peptides generated by proteolysis has not been investigated. Our previous studies have shown that the aminopeptidase III we identified and isolated from lens may be the physiologically important major peptidase in lens. We have now isolated an acylpeptide hydrolase from bovine lenses which can remove N-acetyl amino acids from the peptides. Our studies have also shown that the lens contains aminopeptidases capable of complete hydrolysis of peptides resistant to leucine aminopeptidase indicating a major role for other enzymes in lens. We have proposed to continue our investigations in search of new aminopeptidases in lens. We will also be studying the hydrolysis of specific peptide sequences by lens peptidases, prolyl oligopeptidase and acylpeptide hydrolase. The proposal also includes the study of peptide interaction with crystallins and the effect of peptide accumulation "in vivo".