Research Paper Volume 10, Issue 8 pp 1932—1946
Sirt6 deficiency impairs corneal epithelial wound healing
- 1 Wuhan Hanyang Eyegood Ophthalmic Hospital, Wuhan, China
- 2 Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
- 3 Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 4 Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA
- 5 Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
- 6 Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, TX 77555, USA
Received: June 18, 2018 Accepted: July 29, 2018 Published: August 2, 2018
https://doi.org/10.18632/aging.101513How to Cite
Copyright: Hu et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Corneal transparency, dependent on the integrity of epithelial cells, is essential for vision. Corneal epithelial damage is one of the most commonly observed ocular conditions and proper wound healing is necessary for corneal transparency. Sirt6, a histone deacetylase, has been shown to regulate many cellular events including aging and inflammation. However, its specific role in corneal epithelial wound healing remains unknown. Here we demonstrated that Sirt6 was expressed in corneal epithelial cells and its expression decreased with age. In an in vivo corneal epithelial wound healing model, Sirt6 deficiency resulted in delayed and incomplete wound healing and was associated excessive inflammation in the corneal stroma and dysfunction of Notch signaling, leading to keratinization of the corneal epithelium and corneal opacity. Aging Sirt6-deficient mice spontaneously developed corneal keratitis with extensive infiltration of inflammatory cells into the cornea. In vitro experiments demonstrated that primary corneal epithelial cells with Sirt6 downregulation expressed increased basal levels of inflammatory genes and exhibited hyper-inflammatory reactivity to IL-1β and TNFα treatment. These results provide compelling evidence that Sirt6 is a critical regulator of inflammation in the cornea, and is responsible for corneal epithelial wound healing, thus contributing to the maintenance of epithelial integrity and corneal transparency.