γ-Glutamylcysteine suppresses epithelial-mesenchymal transition in lens epithelial cells to ameliorate diabetic cataract through regulating TGF-β2 and AMPK-related signaling pathways

Diabetic cataract (DC) is a leading cause of blindness globally. Vision impairment in diabetic individuals frequently necessitates surgical intervention for treatment. However, postoperative inflammation response is the major cause of surgery failure. γ-glutamylcysteine (γ-GC), a direct precursor for glutathione (GSH) biosynthesis, has been reported to prevent diabetes. Here, we sought to explore the effects of γ-GC on high glucose (HG)-induced lens epithelial cells (LECs) oxidative damage and cataract formation. Our findings indicated that γ-GC inhibited the onset and progression of cataract in db/db mice. Meanwhile, HLE cells showed severe oxidative damages after HG stimulation; however, γ-GC could significantly rescue HLE cells from oxidative damage-induced apoptosis and inflammation. We further found that γ-GC could inhibit AKR1B1-mediated epithelial-mesenchymal transition (EMT) to ameliorate DC through regulating TGF-β2/Smad/AKT and AMPK-related signaling. Collectively, γ-GC, as a safe and effective natural dipeptide, emerges as a promising candidate for preventing and treating cataract in diabetic patients. • γ-GC improves the development of diabetic cataract. • γ-GC protects lens epithelial cells against oxidative damage. • γ-GC suppresses AKR1B1 accumulation-induced EMT process of lens epithelial cells. • γ-GC alleviates diabetic cataract by regulating TGF-β2 and AMPK-related signaling.