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The FADS mouse: A novel mouse model of atopic keratoconjunctivitis
Satoshi Nunomura1, Isao Kitajima2, Yasuhiro Nanri1
1Division of Medical Biochemistry, Saga Medical School, Saga, Japan.
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 Ikk2Flox/Flox mice to male Nestincre; Ikk2Flox/+ 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 TH2/TC2 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.
Insights
A new mouse model, FADS mice, spontaneously develops atopic keratoconjunctivitis (AKC)-like lesions. This model is effective for evaluating treatments like betamethasone for AKC.
Area of Science:
- Ophthalmology
- Immunology
- Dermatology
Background:
- Atopic keratoconjunctivitis (AKC) is a chronic allergic eye disease.
- A suitable mouse model for AKC research and therapeutic evaluation was lacking.
- Facial AD with scratching (FADS) mice, with Ikk2 deleted in skin fibroblasts, were developed.
Purpose of the Study:
- To assess if FADS mice exhibit ocular lesions similar to human AKC.
- To evaluate the efficacy of topical tacrolimus and betamethasone in FADS mice.
- To utilize tear periostin as a biomarker for allergic conjunctival disease.
Main Methods:
- FADS mice were generated by crossing specific Ikk2-floxed and Nestin-cre mouse lines.
- Histological analysis of ocular lesions was performed.
- Tear periostin levels were measured in untreated and treated FADS mice.
Main Results:
- FADS mice displayed severe blepharitis and facial scratching.
- Ocular lesions showed hyperplasia, inflammation (eosinophils, mast cells, TH2/TC2 cells), and upregulated periostin.
- Betamethasone demonstrated superior efficacy over tacrolimus in reducing corneal lesions and increasing tear periostin.
Conclusions:
- The FADS mouse represents a novel and valuable model for atopic keratoconjunctivitis.
- This model facilitates the examination of therapeutic effects for anti-AKC agents.
- Tear periostin serves as a useful biomarker in this AKC model.
