Lycopene Protects Corneal Endothelial Cells from Oxidative Stress by Regulating the P62–Autophagy–Keap1/Nrf2 Pathway

Abstract

Oxidative stress is a key mechanism in corneal endothelial damage-related diseases, which is induced by environmental factors and genetic mutations. Lycopene (LYC), one of the most potent natural antioxidants, has been shown to offer significant protection against various diseases. However, its role and mechanisms in corneal endothelial damage remain unclear. In this study, an oxidative stress-induced injury model was created using the B4G12 cell line, and a disease model for Fuchs’ endothelial corneal dystrophy (FECD) was established using genetically edited mice, both of which were treated with LYC. The results demonstrated that lycopene effectively protected corneal endothelial cells and slowed the progression of FECD. The protective mechanism involves upregulating P62 and activating autophagy, leading to Keap1 degradation, Nrf2 nuclear translocation, and activation of downstream antioxidant proteins. This study broadens the potential application of lycopene in protecting the corneal endothelium and provides a new non-surgical approach for treating corneal endothelial damage-related diseases.