UVR-B-induced NKR-1 Expression in Ocular Tissues is blocked by Substance P Receptor Antagonist Fosaprepitant in the Exposed as well as Unexposed Partner Eye

Ocul Immunol Inflamm. 2021 Jul 4;29(5):963-975. doi: 10.1080/09273948.2019.1708414. Epub 2020 Feb 14.

Abstract

Purpose: To investigate the effect of NKR-1 antagonists in an established UVR-B-induced cataract mouse model. Furthermore, to examine the expression of pro-inflammatory cytokines/chemokines in mouse eyes following unilateral UVR-B exposure.Methods: Mice received intraperitoneally injections of Fosaprepitant and Spantide I, before and after unilateral exposure to UVR-B. After day 3 and 7 post-exposure, ocular tissues were extracted for the detection of NKR-1 protein level by ELISA.Results: Pretreatment with Fosaprepitant decreases NKR-1 expression in exposed ocular tissues as well as in the unexposed lens epithelium compared to the saline group. Spantide I treatment showed a tendency of NKR-1 overexpression in ocular tissues.Conclusion: The clinically approved NKR-1 receptor antagonist Fosaprepitant decreases NKR-1 protein expression effectively not only in the exposed but also in the unexposed partner eye in a UVR-B irradiation mouse model. No effect was seen on the protein concentration of pro-inflammatory cytokines/chemokines in either eye.

Keywords: Fosaprepitant (IVEMEND®); Spantide I; Ultraviolet radiation B; cytokines/chemokines; neurokinin receptor 1.

MeSH terms

  • Animals
  • Aqueous Humor / drug effects
  • Aqueous Humor / metabolism
  • Cataract / etiology
  • Cataract / metabolism*
  • Choroid / drug effects
  • Choroid / metabolism
  • Ciliary Body / drug effects
  • Ciliary Body / metabolism
  • Cornea / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Injections, Intraperitoneal
  • Iris / drug effects
  • Iris / metabolism
  • Lens, Crystalline / drug effects
  • Lens, Crystalline / metabolism
  • Lens, Crystalline / radiation effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morpholines / pharmacology*
  • Neurokinin-1 Receptor Antagonists / pharmacology*
  • Radiation Injuries, Experimental / etiology
  • Radiation Injuries, Experimental / metabolism*
  • Receptors, Neurokinin-1 / metabolism*
  • Retina / drug effects
  • Retina / metabolism
  • Substance P / analogs & derivatives
  • Substance P / pharmacology
  • Ultraviolet Rays / adverse effects*

Substances

  • Morpholines
  • Neurokinin-1 Receptor Antagonists
  • Receptors, Neurokinin-1
  • Substance P
  • fosaprepitant
  • spantide