Carboxymethyl chitosan regulates macrophages polarization to inhibit early subconjunctival inflammation in conjunctival injury

Int J Biol Macromol. 2023 Jul 31:244:125159. doi: 10.1016/j.ijbiomac.2023.125159. Epub 2023 Jun 1.

Abstract

Persistent subconjunctival inflammation leads to subconjunctival fibrosis and eventual visual impairment. There is an unmet need for how to effectively inhibit subconjunctival inflammation. Herein, the effect of carboxymethyl chitosan (CMCS) on subconjunctival inflammation was investigated and the mechanism was involved. The evaluation of cytocompatibility demonstrated that CMCS had good biocompatibility. The in vitro results showed that CMCS inhibited secretions of pro-inflammatory cytokines (IL-6, TNF-α, IL-8 and IFN-γ) and chemokines (MCP-1), and downregulated TLR4/MyD88/NF-κB pathway in M1. The in vivo results displayed that CMCS alleviated conjunctival edema and congestion, and improved conjunctival epithelial reconstruction significantly. Both in vitro and in vivo results demonstrated that CMCS inhibited the infiltration of macrophages and reduced the expressions of iNOS, IL-6, IL-8 and TNF-α in the conjunctiva. Given that CMCS indicated the activities of inhibiting M1 polarization, NF-κB pathway, and subconjunctival inflammation, which may be employed as a potent treatment for subconjunctival inflammation.

Keywords: Carboxymethyl chitosan; Inflammation; Macrophage polarization; NF-κB; Subconjunctival injury.

MeSH terms

  • Chitosan* / metabolism
  • Chitosan* / pharmacology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages
  • NF-kappa B* / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Chitosan
  • Interleukin-8
  • Lipopolysaccharides