Hypothesized mechanism of the role of protein-S-S-glutathione in lens protein aggregation during cataract formation. Initial step, lens GSH is oxidized to GSSG and accumulated. 2nd step, GSSGs conjugate randomly with the thiol groups of crystallin proteins (native protein) to form protein-S-S-glutathione mixed disulfides (PSSGs). 3rd step, PSSG formation causes conformation change in crystallin proteins. Final step, Protein-S-S-protein (PSSP) crosslinking and/or other protein modifications occur with protein–protein aggregation. These changes lead to protein insolubility, opacification, and even pigmentation. Reprinted with permission from Lou, PRER (2003); Copyright Elsevier 2003 [8].