Nrf2, a Potential Therapeutic Target against Oxidative Stress in Corneal Diseases

Figure 1

Schematic diagram of Nrf2 signaling and regulation in the corneal epithelial cells. 4-HNE or H₂O₂ induces excessive ROS generation (by upregulation of 3-NT, NOX4 protein expression), leading to oxidative stress in the cultured HCE cells and resulting in cell apoptosis and death of corneal epithelial cells. 4-HNE activates Nrf2/ARE-controlled antioxidant enzyme (NQO1 and GSTP) transcription, which facilitates ROS degradation. On the other hand, H₂O₂ decreases Nrf2/ARE-controlled SOD and catalase transcription, leading to ROS degradation suppression. NAC serves as an antioxidant by antagonizing 4-HNE overexpression and reversing the cell viability of HCE cells. SA3K blocks H₂O₂-induced ROS, 3-NT, and NOX4 overexpression and upregulates ROS degradation by activating Keap1-Nrf2-ARE pathway.