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

Area of Science:

• Biochemistry
• Cell Biology
• Ophthalmology

Background:

• Glutaredoxin (Grx) is crucial for antioxidant defense in cataract pathogenesis.
• Previous studies linked Grx knockout to accelerated aging-related cataracts (ARC), but its role in diabetes cataract (DC) remains unclear.

Purpose of the Study:

• To elucidate the regulatory mechanism of Grx in diabetes cataract (DC).
• To investigate the protective effects of Grx against high-glucose-induced oxidative stress and apoptosis in human lens epithelial cells (HLEC-B3).

Main Methods:

• Assessed AMPK activity and Grx expression in DC patient samples and HLEC-B3 cells.
• Evaluated Grx's protective effects on HLEC-B3 cells against high-glucose (HG) induced injury, apoptosis, and mitophagy.
• Utilized AMPK inhibitor (Compound C) and BNIP3 knockdown to examine underlying mechanisms.
• Investigated Grx's role in vivo in a rat model of DC.

Main Results:

• AMPK activity was decreased, while Grx expression and activity were increased in DC anterior lens capsules and HG-treated HLEC-B3 cells.
• Grx conferred protection against HG-induced oxidative stress, apoptosis, and promoted mitophagy in HLEC-B3 cells.
• AMPK inhibition and BNIP3 knockdown abrogated Grx's protective effects.
• In vivo, Grx alleviated DC by inhibiting oxidative damage, with effects reversed by Compound C.

Conclusions:

• Grx alleviates diabetes cataract (DC) by activating AMPK, which subsequently induces BNIP3/BNIP3L-mediated mitophagy.
• This study identifies a novel mechanism for Grx in DC pathogenesis and suggests potential therapeutic targets for DC treatment.