VIP modulates the ALX/FPR2 receptor axis toward inflammation resolution in a mouse model of bacterial keratitis

Thomas W Carion1, David Kracht1, Eliisa Strand1

  • 1Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, United States.

Insights

Vasoactive intestinal peptide (VIP) treatment effectively reduces bacterial keratitis severity in mice. This peptide influences the formyl peptide receptor 2 (FPR2) pathway, offering a potential therapeutic strategy for eye infections.

Area of Science:

  • Ophthalmology
  • Immunology
  • Pharmacology

Background:

  • Corneal inflammation is a significant cause of vision impairment.
  • Vasoactive intestinal peptide (VIP) is known to modulate inflammatory processes.
  • Formyl peptide receptor 2 (FPR2) is implicated in inflammation resolution.

Purpose of the Study:

  • To investigate the therapeutic potential of VIP in bacterial keratitis.
  • To elucidate the role of the VIP-FPR2 axis in disease outcome.
  • To explore VIP's mechanism of action in resolving inflammation.

Main Methods:

  • Bacterial keratitis was induced in C57BL/6 mice using Pseudomonas aeruginosa.
  • Mice received topical VIP or PBS treatment post-infection.
  • Clinical scores, bacterial load, and inflammatory markers (Griess, MPO) were assessed.

Main Results:

  • Topical VIP treatment significantly reduced clinical scores and bacterial counts.
  • VIP treatment effectively abrogated the inflammatory disease response.
  • VIP's effects on FPR2 pathway activation were observed independently of canonical VIP receptors.

Conclusions:

  • VIP demonstrates therapeutic efficacy in a mouse model of bacterial keratitis.
  • VIP influences the FPR2 pathway, suggesting a novel immunoresolving mechanism.
  • Targeting the VIP-FPR2 axis presents a potential therapeutic intervention for bacterial keratitis.

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