Activation of the Nrf2/HO-1 axis attenuated ischemia–reperfusion injury and improved neurological function [37]; Accordingly, we identified restrained Dll4/Notch signaling by activation of Nrf2. Global Nrf2 deficiency blocked the protection effect of H2, suppressing retinal revascularization and increasing pathologic neovascularization with Dll/Notch up-regulation in OIR mice.The findings from in vivo experiments strongly confirm the notion that activating Nrf2 leads to the beneficial effects of reducing reactive oxygen species (ROS) and inhibiting the Dll4/Notch signaling pathway. The gene discussed is DLL4; the disease is ischemia.