d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions.

Abstract Cataract is the leading cause of blindness with an estimated 16 million people affected worldwide. d -galactose ( d -gal) is a reducing sugar that widely distributed in foodstuffs, and studies show that d -gal could promote cataract formation by damaging nature lens epithelial cells (LECs). However, the underlying mechanism is unclear. In our present study, d -gal resulted in premature senescence of LECs, which was confirmed by determining the β-galactosidase activity, cell proliferative potential and cell cycle distribution, though apoptosis of LECs was not observed. We also verified that d -gal induced the impairment of autophagy flux by measuring the expression of LC3II and P62. Meanwhile, we found that d -gal induced mitochondrial dysfunctions of LECs through increasing reactive oxygen species (ROS), reducing ATP synthesis and mitochondrial potential (MMP), enhancing the concentration of cytoplasm Ca 2+ and permeability transition pore (mPTP) opening. Metformin, as a potential anti-aging agent, suppressed the senescence of LECs by restoring autophagy flux and mitochondria functions. Nevertheless, the antioxidant N-acetylcysteine (NAC) scavenged ROS significantly but was not efficient in preventing LECs from premature senescence. Our data suggests that restoring autophagy activity and improving mitochondrial functions may be a potential strategy for the prevention of LECs senescence-related cataract.