Grx attenuates diabetes cataract by activating AMPK/BNIP3/BNIP3L-mediated mitophagy in lens epithelial cells.

Glutaredoxin (Grx) plays an important antioxidant role in the pathogenesis of cataracts. Our previous research found that Grx knockout accelerated the occurrence of aging-related cataract (ARC) and was closely related to lens opacity, but the regulatory mechanism of Grx in diabetes cataract (DC) is still unclear. Here, we found that AMPK activity was significantly decreased in the anterior lens capsule of DC patients and high-glucose (HG) treated human lens epithelial cells HLEC-B3, and Grx protein expression and activity were compensatory increased. Moreover, Grx protected HLEC-B3 cells from HG-induced oxidative stress injury and apoptosis, and induced mitophagy. Both AMPK inhibitor (Compound C) and BNIP3 knockdown attenuated these effects. In vivo, Grx alleviated DC by inhibiting oxidative damage, whereas Compound C reversed the protective effect of Grx. In summary, our findings suggest that Grx alleviates DC in rats by activating AMPK to induce BNIP3/BNIP3L-mediated mitophagy. This study provides new experimental evidence and potential targets for the future treatment of DC.