Amarnani Dhanesh, Sanchez Angie V, Wong Lindsay L, Duffy Brandon V, Ramos Leslie, Freitag Suzanne K, Bielenberg Diane R, Kim Leo A, Lee Nahyoung Grace
Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Harvard College, Cambridge, MA, USA.
Transl Vis Sci Technol. 2020 Jul 16;9(8):26. doi: 10.1167/tvst.9.8.26. eCollection 2020 Jul.
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.
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.
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.
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.
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.
严重的急性眼眶炎症可导致不可逆的视力丧失。迄今为止，治疗方法仅限于全身使用类固醇或眼眶手术减压。一种能够模拟甲状腺眼病中急性眼眶炎症特征的动物模型可用于探索新的治疗方式。
我们通过将恶唑酮注射到小鼠眼眶中建立了眼眶炎症的小鼠模型。对小鼠进行磁共振成像（MRI）检查，并在不同时间点实施安乐死以进行组织学检查。进行了特定炎症细胞的免疫荧光研究和细胞因子阵列分析。
我们发现小鼠模型与人类疾病在临床和影像学上具有一致性。72小时后，致敏小鼠在注射侧眼睑出现眶周皮炎和炎症。到一周时，注射眼的眼球突出增加，伴有明显的眼睑水肿。到四周时，炎症和眼球突出减轻。在所有三个时间点，小鼠均表现出眼球突出和眶周水肿。组织病理学上，包括T细胞、巨噬细胞和中性粒细胞在内的炎症细胞群体与甲状腺眼病患者的样本具有相似性。炎症和血管生成标志物水平的蛋白质组学变化与甲状腺眼病患者中观察到的预期血管生成、炎症和纤维化反应相关。
使用恶唑酮建立的眼眶炎症小鼠模型概括了甲状腺眼病以及可能其他非特异性眼眶炎症的一些临床特征，其典型表现为炎症细胞浸润、眼眶组织扩张和重塑以及随后的纤维化。
这种动物模型可以作为一个可行的平台，用于了解急性眼眶炎症的潜在机制，并研究潜在的新的靶向治疗方法。
