Rocking media over ex vivo corneas improves this model and allows the study of the effect of proinflammatory cytokines on wound healing

Invest Ophthalmol Vis Sci. 2015 Feb 5;56(3):1553-61. doi: 10.1167/iovs.14-15308.

Abstract

Purpose: The aim of this work was to develop an in vitro cornea model to study the effect of proinflammatory cytokines on wound healing.

Methods: Initial studies investigated how to maintain the ex vivo models for up to 4 weeks without loss of epithelium. To study the effect of cytokines, corneas were cultured with the interleukins IL-17A, IL-22, or a combination of IL-17A and IL-22, or lipopolysaccharide (LPS). The effect of IL-17A on wound healing was then examined.

Results: With static culture conditions, organ cultures deteriorated within 2 weeks. With gentle rocking of media over the corneas and carbon dioxide perfusion, the ex vivo models survived for up to 4 weeks without loss of epithelium. The cytokine that caused the most damage to the cornea was IL-17A. Under static conditions, wound healing of the central corneal epithelium occurred within 9 days, but only a single-layered epithelium formed whether the cornea was exposed to IL-17A or not. With rocking of media gently over the corneas, a multilayered epithelium was achieved 9 days after wounding. In the presence of IL-17A, however, there was no wound healing evident. Characterization of the cells showed that wherever epithelium was present, both differentiated cells and highly proliferative cells were present.

Conclusions: We propose that introducing rocking to extend the effective working life of this model and the introduction of IL-17A to this model to induce aspects of inflammation extend its usefulness to study the effects of agents that influence corneal regeneration under normal and inflamed conditions.

Keywords: cornea organ culture; inflammation; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cornea / drug effects*
  • Culture Media*
  • Culture Techniques* / instrumentation
  • Epithelium, Corneal / drug effects
  • Interleukin-17 / pharmacology*
  • Interleukin-22
  • Interleukins / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Organ Culture Techniques / instrumentation*
  • Rabbits
  • Regeneration / drug effects
  • Wound Healing / drug effects*

Substances

  • Culture Media
  • Interleukin-17
  • Interleukins
  • Lipopolysaccharides