Oxidation-Induced Mixed Disulfide and Cataract Formation: A Review

The major function of eye lens is to transmit light onto retina and form an image. This relies on the crystallin proteins, which are tightly packed to achieve a high refractive index and transparency. The proteins are protected and maintained in a reduced state with intrinsic antioxidants, such as glutathione (GSH), and redox-regulating enzyme systems, such as thioltransferase to maintain the SH/-S-S-balance. When the protective systems are impaired or reduced due to aging, oxidative stress can lead to SH/S-S imbalance, protein modification, protein-protein aggregation and loss of transparency (cataract). Oxidative stress is considered the major culprit in senile cataract formation since cataractous lenses are typically low in GSH content and have elevated levels of GS-protein mixed disulfide (PSSG). This review will examine PSSG accumulation with age and cataracts and explore the possible role of oxidants such as H₂O₂. It will also discuss the hypothesis that PSSG formation is not simply a consequence of cataract formation but can trigger the cascade of events leading to loss of lens transparency. The hypothesis is supported by the findings that cataract formation is more rapid with increasing age due to weaker TTase activity and, in animal model systems, when the TTase gene is deleted.