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Zeb1 Facilitates Nitrogen Mustard-Induced Corneal Epithelial Wound Healing by Maintaining Epithelial Renewability
Fuhua Wang1,2, Xiaolei Sun1,2, Yanling Dong3
1Department of Medicine, University of Louisville, Louisville, Kentucky, United States.
Purpose:
To characterize Zeb1 regulation of nitrogen mustard (NM)-induced acute corneal epithelial damage and its recovery in mice.
Methods:
This study utilized topical fluorescein staining and section immunohistochemistry to evaluate NM-induced acute corneal epithelial damage and its recovery in both Zeb1 wild-type and heterozygous knockout mice, as well as real-time quantitative PCR and chromatin immunoprecipitation to delineate the mechanism underlying Zeb1 regulation of such corneal epithelial damage and recovery.
Results:
Topical application of NM on the central cornea causes an immediate reduction of Zeb1 expression, followed by de-epithelization and epithelial cell death, along with cell proliferation resulting in epithelial recovery. Monoallelic knockout of Zeb1 decreased NM-induced acute epithelial damage but delayed the recovery from the damage.
Conclusions:
Zeb1 facilitates NM-induced corneal epithelial wound healing by maintaining epithelial renewability and thus is a potential therapeutic target to reduce acute mustard gas keratopathy in early ocular pathogenesis.
