AI Article Synopsis
- The study introduces a new mouse model named FADS (facial AD with scratching), which develops symptoms similar to atopic keratoconjunctivitis (AKC) due to the deletion of the Ikk2 gene in skin fibroblasts.
- Researchers evaluated the ocular lesions in FADS mice to see if they resembled human AKC, and measured a biomarker called tear periostin to assess treatment efficacy.
- The findings showed that FADS mice had significant eye issues and that the medication betamethasone was more effective than tacrolimus in reducing corneal damage and affecting tear periostin levels, highlighting the model's potential for testing AKC treatments.
Article Abstract
Background: Atopic keratoconjunctivitis (AKC) is a chronic allergic conjunctival disease. However, a mouse model of AKC to investigate the underlying mechanism of the therapeutic agents and estimate their efficacy has not been established. We recently generated mice in which Ikk2 is specifically deleted in facial skin fibroblasts and found that these mice spontaneously develop atopic dermatitis (AD)-like facial skin inflammation and scratching behaviors; thus, we named them facial AD with scratching (FADS) mice.
Objective: We sought to evaluate whether the ocular lesions that FADS mice spontaneously develop are similar to those of patients with AKC and to estimate the efficacy of topical treatments with tacrolimus and betamethasone for FADS mice by using tear periostin, a novel biomarker for allergic conjunctival disease.
Methods: FADS mice, in which Ikk2 is deleted in dermal fibroblasts, were generated by crossing female Ikk2 mice to male Nestin; Ikk2 mice. We conducted histologic analysis of the ocular lesions in FADS mice. Furthermore, we measured periostin in the tears collected from FADS mice untreated or treated with tacrolimus or betamethasone.
Results: The FADS mice exhibited severe blepharitis and scratch behaviors for their faces. In these mice, corneal epithelium and stroma showed hyperplasia and infiltration of eosinophils, mast cells, and T2/T2 cells. Periostin was significantly expressed in the lesions and tear periostin was upregulated. Betamethasone showed more suppressive effects than did tacrolimus on severe corneal lesions and increased tear periostin level.
Conclusions: The FADS mouse is a novel mouse model of AKC and is useful to examine the therapeutic effects of anti-AKC agents.
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Source |
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| http://dx.doi.org/10.1016/j.jaci.2021.05.017 | DOI Listing |
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