The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion

Mengliang Wu, Laura E Downie, Lisa J Hill, Holly R Chinnery

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Corneal immune cells interact with corneal sensory nerves during both homeostasis and inflammation. This study sought to evaluate temporal changes to corneal immune cell density in a mouse model of epithelial abrasion and nerve injury, and to investigate the immunomodulatory effects of topical decorin, which we have shown previously to promote corneal nerve regeneration.

METHODS: Bilateral corneal epithelial abrasions (2 mm) were performed on C57BL/6J mice. Topical decorin or saline eye drops were applied three times daily for 12 h, 24 h, 3 days or 5 days. Optical coherence tomography imaging was performed to measure the abrasion area. The densities of corneal sensory nerves (β-tubulin III) and immune cells, including dendritic cells (DCs; CD11c+), macrophages (Iba-1+) and neutrophils (NIMP-R14+) were measured. Cx3cr1gfp/gfp mice that spontaneously lack resident corneal intraepithelial DCs were used to investigate the specific contribution of epithelial DCs. Neuropeptide and cytokine gene expression was evaluated using qRT-PCR at 12 h post-injury.

RESULTS: In decorin-treated corneas, higher intraepithelial DC densities and lower neutrophil densities were observed at 24 h after injury, compared to saline controls. At 12 h post-injury, topical decorin application was associated with greater re-epithelialisation. At 5 days post-injury, corneal stromal macrophage density in the decorin-treated and contralateral eyes was lower, and nerve density was higher, compared to eyes treated with saline only. Lower expression of transforming growth factor beta (TGF-β) and higher expression of CSPG4 mRNA was detected in corneas treated with topical decorin. There was no difference in corneal neutrophil density in Cx3cr1gfp/gfp mice treated with or without decorin at 12 h.

CONCLUSIONS: Topical decorin regulates immune cell dynamics after corneal injury, by inhibiting neutrophils and recruiting intraepithelial DCs during the acute phase (< 24 h), and inhibiting macrophage density at the study endpoint (5 days). These immunomodulatory effects were associated with faster re-epithelialisation and likely contribute to promoting sensory nerve regeneration. The findings suggest a potential interaction between DCs and neutrophils with topical decorin treatment, as the decorin-induced neutrophil inhibition was absent in Cx3cr1gfp/gfp mice that lack corneal epithelial DCs. TGF-β and CSPG4 proteoglycan likely regulate decorin-mediated innate immune cell responses and nerve regeneration after injury.

Original languageEnglish
Article number90
JournalJournal of Neuroinflammation
Volume19
Issue number1
DOIs
Publication statusPublished - 12 Apr 2022

Bibliographical note

Funding Information:
Funding support provided by the National Health and Medical Research Council (Australia) (HRC, APP1126540) and the Australian Government Research Training Program (MW).

Publisher Copyright:
© 2022, The Author(s).

Keywords

  • Animals
  • Cornea
  • Corneal Injuries/drug therapy
  • Decorin
  • Mice
  • Mice, Inbred C57BL
  • Transforming Growth Factor beta/genetics
  • Small leucine-rich proteoglycan
  • Wound healing
  • Dendritic cells
  • Neutrophils
  • Macrophages
  • Nerve regeneration

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Immunology

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