Sleep deprivation induces corneal epithelial progenitor cell over-expansion through disruption of redox homeostasis in the tear film

Stem Cell Reports. 2022 May 10;17(5):1105-1119. doi: 10.1016/j.stemcr.2022.03.017. Epub 2022 Apr 28.

Abstract

Sleep deficiency, a common public health problem, causes ocular discomfort and affects ocular surface health. However, the underlying mechanism remains unclear. Herein, we identified that short-term sleep deprivation (SD) resulted in hyperproliferation of corneal epithelial progenitor cells (CEPCs) in mice. The expression levels of p63 and Keratin 14, the biomarkers of CEPCs, were upregulated in the corneal epithelium after short-term SD. In addition, SD led to elevated levels of reactive oxygen species (ROS), and subsequent decrease in antioxidant capacity, in the tear film. Exogenous hydrogen peroxide (H2O2) could directly stimulate the proliferation of CEPCs in vivo and in vitro. Topical treatment of antioxidant L-glutathione preserved the over-proliferation of CEPCs and attenuated corneal epithelial defects in SD mice. Moreover, the activation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is essential to ROS-stimulated cell proliferation in CEPCs. However, long-term SD ultimately led to early manifestation of limbal stem cell deficiency.

Keywords: ROS; cell proliferation; cornea; dry eye; epithelial progenitor cell; lacrimal gland; limbal stem cell; sleep deprivation; stem cell; tear film.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Cell Proliferation
  • Epithelium, Corneal*
  • Homeostasis
  • Hydrogen Peroxide / metabolism
  • Mice
  • Oxidation-Reduction
  • Phosphatidylinositol 3-Kinases / metabolism
  • Reactive Oxygen Species / metabolism
  • Sleep Deprivation* / metabolism
  • Stem Cells / metabolism

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Hydrogen Peroxide