Age-related cleavages of crystallins in human lens cortical fibre cells generate a plethora of endogenous peptides and high molecular weight complexes

Age-related breakdown of lenticular crystallins is associated with lenticular disorders such as cataract. Despite playing a critical role in maintaining lens homeostasis, the mechanism(s) and consequences of this phenomenon are not well understood. Utilising a proteomic-based approach, this study characterised 238 endogenous peptides derived from age-related crystallin breakdowns present in the cortical tissues of young, middle-age and old human lenses. Quantitative mass spectrometry analysis showed that the concentration of a prominent crystallin breakdown product in the lens increased significantly with age, which, coupled with the age-related increase in variety of the LMW crystallin peptide in the lens cortex, suggests that a major crystallin breakdown event taking place in the human lens cortex shortly after middle-age. In-depth analysis on the crystallin peptide terminal amino acids indicate the presence of trypsin-like proteolysis in the lens cortical cells, providing useful information on the mechanism(s) that contribute to crystallin breakdown in the aging human lens. Taken together, this work enhances our understanding on the age-related crystallin breakdown process in the cortical tissues of the human lens.