Oxidative Stress in Genetic Cataract Formation

Cataracts are the leading cause of blindness worldwide, and age-related cataracts are the result of environmental insults that largely lead to oxidative stress imposed on a genetic background that determines susceptibility to these stresses.

A comprehensive literature review was performed to identify GWAS, targeted association studies, and TWAS that identified genes associated with age-related cataract. Additional genes associated with age-related cataracts were identified through the CAT-MAP online database. Pathway analysis was performed using Qiagen Ingenuity Pathway Analysis and pathways related to oxidative stress were analyzed using the same program.

A large number of genes have been identified as causes of both Mendelian and complex cataracts. Of these, 10 genes related to oxidative stress were identified, and all were associated with age-related cataracts. These genes fall into seven canonical pathways primarily related to glutathione metabolism and other pathways related to detoxifying reactive oxygen species.

While a relatively small number of antioxidant related genes were identified as being associated with cataracts, they allow the identification of redox pathways important for lens metabolism and homeostasis. These are largely related to glutathione and its metabolism, other pathways for detoxification of reactive oxygen species, and the transcriptional systems that control their expression.