<scp>DJ</scp> ‐1 in human lenses: Potential role in preventing advanced glycation endproduct formation

The amino groups of lysine and arginine residues in proteins react with reducing sugars and carbonyl compounds to form advanced glycation endproducts (AGEs). Several AGEs have been detected in human lenses, and their levels have been shown to increase with age and cataract formation. AGEs can lead to structural changes, yellow pigmentation, and cross-linking of lens proteins. Studies have shown a positive correlation between AGEs levels and lens age, stiffness, and cataracts. Recent research suggests that DJ-1 can inhibit the accumulation of AGEs in cellular proteins by reversing the early glycation steps. Our study found that DJ-1 is present in epithelial cells and the outer cortex of the human lens. DJ-1 is catalytically active in human lenses, and its ability to metabolize methylglyoxal (MGO) into D-lactate diminishes as the lens ages. The formation of MGH-1 from MGO was promoted in lens proteins treated with the DJ-1 inhibitor. Recombinant DJ-1 prevents α-dicarbonyl-mediated cross-linking and AGE accumulation in human αB-crystallin. DJ-1 prevents glyoxal-mediated cell death and AGE accumulation in human lens epithelial cells. Taken together, our results suggest that DJ-1 in the human lens hinders AGE accumulation. Enhancing its activity using pharmacological agents can potentially delay or prevent the onset of presbyopia and cataracts.