Figure 4.

Cataract viewed as a protein aggregation disease. Crystallin proteins, particularly in the lens nucleus, are present from birth and over time accumulate covalent modifications and damages resulting from proteolytic activity, non-enzymatic modifications, and oxidative damage. This leads to destabilization and partial unfolding of the polypeptide chains and a population of aggregation-prone intermediates. In young lenses, α-crystallin effectively recognizes and sequesters these destabilized intermediates (upper pathway). However, with age α-crystallin complexes become saturated with substrate and lens proteins are able to aggregate, resulting in light scatter and loss of visual acuity (lower pathway). Reprinted with permission from [54].