Thinking inside the box: Current insights into targeting orbital tissue remodeling and inflammation in thyroid eye disease.
Thinking inside the box: Current insights into targeting orbital tissue remodeling and inflammation in thyroid eye disease.
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DOI：
10.1016/j.survophthal.2021.08.010
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发表时间：
2022-05
影响因子：
5.1
通讯作者：
Woeller CF
中科院分区：
文献类型：
--
作者：
Gupta V;Hammond CL;Roztocil E;Gonzalez MO;Feldon SE;Woeller CF
甲状腺眼病（TED）是一种表现于眼眶的自身免疫性疾病。在TED中，眼睛后面的结缔组织会发炎，并随着脂肪堆积和/或肌肉和疤痕组织的增加而重塑。随着眼眶组织扩张，患者出现水肿、眼球突出、复视和视神经病变。在严重的情况下，由于暴露或视神经压迫造成的角膜瘢痕可能继发发生视力丧失。目前还没有治愈TED的方法，治疗方法也很有限。随着FDA批准teprotumumab，一种单克隆胰岛素样生长因子1受体（IGF1R）阻断抗体，TED治疗取得了重大突破。然而，teprotumumab治疗有其局限性，包括成本、输注给药方式、可变反应和复发。我们描述了靶向眼眶成纤维细胞的方法和复杂的病理生理学，这是组织重塑和炎症驱动TED的基础。在阐明TED机制方面的进一步进展可能导致基于早期生物标志物的预防，以及导致更方便，更便宜的治疗。
Thyroid eye disease (TED) is an autoimmune disorder that manifests in the orbit. In TED, the connective tissue behind the eye becomes inflamed and remodels with increased fat accumulation and/or increased muscle and scar tissue. As orbital tissue expands, patients develop edema, exophthalmos, diplopia, and optic neuropathy. In severe cases, vision loss may occur secondary to corneal scarring from exposure or optic nerve compression. Currently there is no cure for TED, and treatments are limited. A major breakthrough in TED therapy occurred with the FDA approval of teprotumumab, a monoclonal insulin-like growth factor 1 receptor (IGF1R) blocking antibody. Yet, teprotumumab therapy has limitations, including cost, infusion method of drug delivery, variable response, and relapse. We describe approaches to target orbital fibroblasts and the complex pathophysiology that underlies tissue remodeling and inflammation driving TED. Further advances in the elucidation of the mechanisms of TED may lead to prophylaxis based upon early biomarkers as well as lead to more convenient, less expensive therapies.
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