Short-term azithromycin treatment promotes cornea allograft survival in the rat

PLoS One. 2013 Dec 9;8(12):e82687. doi: 10.1371/journal.pone.0082687. eCollection 2013.

Abstract

Background: Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats.

Methods: Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+), CD4(+), CD8(+), CD25(+), CD161(+) and CD163(+) cells were quantified via immunohistochemistry.

Results: AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls.

Conclusions: Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / pharmacology
  • Allografts
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Azithromycin / administration & dosage
  • Azithromycin / pharmacology*
  • Cornea / drug effects
  • Cornea / pathology
  • Corneal Transplantation*
  • Female
  • Graft Survival / drug effects*
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Keratoplasty, Penetrating / methods
  • Models, Animal
  • Rats

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Azithromycin

Grants and funding

This study was supported by Laboratoires Théa, France. The funders had no role in data collection and analysis, decision to publish, or preparation of the manuscript.