To identify the potential role of signal transductions in regulating hyperglycemia-induced oxidative damage in RGCs, we cultured RGCs in medium supplemented with different concentrations of glucose for at least 3 weeks to establish long-term hyperglycemia status and then detected changes in the expression of Nrf2, Keap1 (Kelch-like ECH-associated protein 1), HIF-1α, ALDH3A1, HO-1, TGF-β1, and TGF-β2 proteins in response to hyperglycemia. This evidence concerns the gene NFE2L2 and Hyperglycemia.