A stochastic model of corneal epithelium maintenance and recovery following perturbation

J Math Biol. 2019 Apr;78(5):1245-1276. doi: 10.1007/s00285-018-1308-9. Epub 2018 Nov 26.

Abstract

Various biological studies suggest that the corneal epithelium is maintained by active stem cells located in the limbus, the so-called limbal epithelial stem cell hypothesis. While numerous mathematical models have been developed to describe corneal epithelium wound healing, only a few have explored the process of corneal epithelium homeostasis. In this paper we present a purposefully simple stochastic mathematical model based on a chemical master equation approach, with the aim of clarifying the main factors involved in the maintenance process. Model analysis provides a set of constraints on the numbers of stem cells, division rates, and the number of division cycles required to maintain a healthy corneal epithelium. In addition, our stochastic analysis reveals noise reduction as the epithelium approaches its homeostatic state, indicating robustness to noise. Finally, recovery is analysed in the context of perturbation scenarios.

Keywords: Chemical master equation; Corneal epithelium homeostasis and recovery; ODE and stochastic model.

MeSH terms

  • Animals
  • Cell Count
  • Cell Movement
  • Cell Proliferation
  • Corneal Injuries / pathology
  • Corneal Injuries / physiopathology
  • Epithelium, Corneal / cytology*
  • Epithelium, Corneal / injuries
  • Epithelium, Corneal / physiology*
  • Homeostasis
  • Humans
  • Mathematical Concepts
  • Mice
  • Models, Biological*
  • Rabbits
  • Rats
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Stochastic Processes
  • Wound Healing / physiology