Characterization of a Murine Model of Oxazolone-Induced Orbital Inflammation

PURPOSE: Acute orbital inflammation can lead to irreversible vision loss in serious cases. Treatment thus far has been limited to systemic steroids or surgical decompression of the orbit. An animal model that mimics the characteristic features of acute orbital inflammation as found in thyroid eye disease can be used to explore novel treatment modalities. METHODS: We developed a murine model of orbital inflammation by injecting oxazolone into the mouse orbit. The mice underwent magnetic resonance imaging (MRI) and were euthanized at various time points for histologic examination. Immunofluorescence studies of specific inflammatory cells and cytokine arrays were performed. RESULTS: We found clinical and radiographic congruity between the murine model and human disease. After 72 hours, sensitized mice exhibited periorbital dermatitis and inflammation in the eyelids of the injected side. By one week, increased proptosis in the injected eye with significant eyelid edema was appreciated. By four weeks, inflammation and proptosis were decreased. At all three time points, the mice demonstrated exophthalmos and periorbital edema. Histopathologically, populations of inflammatory cells including T cells, macrophages, and neutrophils shared similarities with patient samples in thyroid eye disease. Proteomic changes in the levels of inflammatory and angiogenic markers correlated to the expected angiogenic, inflammatory, and fibrotic responses observed in patients with thyroid eye disease. CONCLUSIONS: A murine model of orbital inflammation created using oxazolone recapitulates some of the clinical features of thyroid eye disease and potentially other nonspecific orbital inflammation, typified by inflammatory cell infiltration, orbital tissue expansion and remodeling, and subsequent fibrosis. TRANSLATIONAL RELEVANCE: This animal model could serve as a viable platform with which to understand the underlying mechanisms of acute orbital inflammation and to investigate potential new, targeted treatments.