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| Inducer | Suppressor | Type | Models | Results | Reference |
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| 4-HNE | NAC | In vitro | Cultured HCE cells | NAC antagonized the 4-HNE-induced oxidant effects in the cultured HCE cells by the reversed cell viability of HCE cells and reduced the 3-NT, NOX4, and Nrf2 protein expression induced by 4-HNE. | [24] |
| H2O2 | SA3K | In vitro | Cultured HCE cells | SA3K reversed H2O2-induced cell apoptosis. SA3K upregulated H2O2-induced downregulation of SOD2 and catalase gene expression. SA3K blocked H2O2-induced ROS and NOX4 overexpression and activated Keap1-Nrf2 pathway by suppressing Keap1-Nrf2-ARE pathway. | [2] |
| In vivo | Rat corneal epithelium | SA3K ameliorated H2O2-induced corneal epithelium death and decreased the H2O2-induced ROS, 3-NT, NOX4, and Nrf2 overexpression. |
| | H2O2 | In vitro | Cultured TKE2 and MCE | TKE2 cells have different homeostasis and strong antioxidant properties compared to MCE by decreasing ROS production and NOX4 and increasing DUSP6, Nrf2, SOD, and GSTP. | [25] |
| Ebselen | | In vitro | hOEC sheet, human corneal limbal tissue | Ebselen maintained the high ATP levels, normal morphology, viability, and function of the hOEC sheets by reducing ROS generation, inducing the Nrf2 activation, decreasing the lactate dehydrogenase (LDH) releasement, and increasing the glutathione (GSH)/oxidized glutathione (GSSG) ratio. Ebselen maintained the normal morphology of limbal epithelial layer and showed meaningfully higher colony-forming efficiency. | [25] |
| Carnosol | | In vivo | Diabetic rat corneal epithelium injury model | Carnosol accelerated the corneal epithelial wound healing. | [16] |
| EP | | In vitro | Cultured keratocytes and myofibroblasts | EP enhanced the Nrf2-mediated antioxidant response and induced phenotypic changes of quiescent corneal stromal keratocytes into contractile myofibroblasts. | [20] |
| TSA | TGF-β | In vitro | Cultured corneal fibroblasts (HTK) | TSA inhibited of TGF-β-stimulated myofibroblast differentiation in HTK cell line, by decreasing ROS and H2O2 accumulation, inducing Nrf2 nuclear translocation and upregulated the transcriptions of Nrf2-ARE-controlled antioxidant enzymes (such as GSH). | [22] |
| Lower fluences of UV-A | | In vitro | CECs | Lower fluences of UV-A activated the antioxidant defense regulated by Nrf2 and higher fluences initiated p53 and caspase-3. UV-A may be related to the etiology of FECD. | [57] |
| | | In vitro | FECD endothelium | Nrf2 is downregulated in FECD endothelium; higher levels of oxidative DNA damage and apoptosis of CE were also detected in FECD endothelium in contrast with normal controls. | [30] |
| tBHP | | In vitro | HCECi and FECDi; FECD corneal buttons | Declined levels of DJ-1 in FECD at baseline and under the condition of oxidative stress were in relation with weakened Nrf2 nuclear translocation and improved cell susceptibility to apoptosis. | [33] |
| UV-A | | In vitro | CECs | Downregulation of DJ-1 resulted in decreased Nrf2 gene expression as well as its target genes HO-1 and NQO1, which inhibits translocation of Nrf2, leading to attenuate the expression of antioxidant gene and increase oxidative damage. The decrease of DJ-1 level results in enhanced CECs susceptibility to UV-A light via inducing p53-dependent apoptosis. | [41] |
| SFN | | In vitro | HCECi and FECDi | SFN increased the activation of Nrf2 in FECD specimens under the condition of oxidative stress. Pretreatment with SFN improved cell viability via diminishing the production of intracellular ROS in FECD. | [46] |
| | SLC4A11 mutations | In vitro | HEK 293 cells | Mutations in the SLC4A11 gene can induce ROS generation and mitochondrial dysfunction because of oxidative stress. HO-1, NQO, and NRF2 expression declined drastically, and a higher apoptosis rate was found in cells with mutant proteins under oxidative stress. | [4] |
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