Although homocysteine activates the Nrf2-mediated antioxidant response, which can protect cells from oxidative damage [52], chronic hyperhomocysteinemia downregulates Nrf2-responsive genes including Sod2, in retinal Muller cells, and Nrf2-lacking mice exposed to chronic high homocysteine have poor visual acuity, suggesting a role of homocysteine in the regulation of Nrf2-mediated antioxidant response and visual function [53,54]. Here, NFE2L2 is linked to hyperhomocysteinemia.