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. 2020 Jun 18;10:9907. doi: 10.1038/s41598-020-66735-x

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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NRF2 target genes significantly altered in KCN corneas. (A) Decreased NRF2 target gene expression in KC and KJ RNA seq. (B) Mechanism of NRF2 regulation by KEAP1; the latter binds to NRF2 and CUL3 for NRF2-ubiquitination and degradation to maintain low levels of NRF2 under homeostatic conditions. Under oxidative stress, KEAP1 dissociates from NRF2 allowing its increase and upregulation of target genes.