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목적 : Graves’ orbitopathy (GO) is a complication in Graves’ disease but mechanistic insights into pathogenesis remain unresolved, hampered by lack of animal model. In this study, we developed the mouse model for GO by immunization with human TSH receptor (hTSHR) plasmid, and we showed alteration of histologic and hematologic signs.
방법 : Female BALB/c mice were challenged with TSHR plasmid by i.m. on three occasions at 4-wk intervals. We measured the thyroid function including serum T3, T4 and TSH levels in TSHR-immunized mice at 8 weeks after end of immunization. The mice were evaluated for orbital remodeling by histopathology and magnetic resonance imaging (MRI).
결과 : The immunization with TSHR in BALB/c mice markedly induced thyroid hypertrophy (1.98 fold of thyroid weight in control, p<0.001) and elevation of intraocular pressure (25.33 mmHg). A striking finding that TSHR-immunized mice shown orbital muscle hypertrophy in vivo MRI scans. Orbital pathology was characterized by interstitial inflammation and fiborsis of extraocular muscles with CD4+ T cells, IL-6 /INF-γ + B cells, and IL-1β/TGF β + fibroblasts in TSHR-immunized mice via NF-κB signaling. The TSHR-immunized mice were significantly increased both serum and orbital hyaluronan levels.
결론 : Overall, these findings support TSHR as the pathogenic antigen in GO. Development of experimental animal model for TSHR-immunized GO will facilitate molecular investigations on GO and evaluation of new therapeutic interventions.
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