从实验室到临床的成功转化——甲状腺相关性眼病治疗重大进展

A successful transition from bench to bedside:Breakthrough in the treatment of thyroid-associated ophthalmopathy

甲状腺相关眼病(TAO)是与Graves'病(GD)密切相关的一种自身免疫性疾病。表观遗传学因素和环境因素都与GD和TAO的发生发展有关。促甲状腺激素受体(TSHR)和胰岛素样生长因子-1受体(IGF-1R)在TAO患者眼眶组织中较正常人高表达,且组成功能复合体,参与GD和TAO相关的信号传导。眼眶成纤维细胞是TAO的靶细胞和效应细胞。近期的研究发现眼眶成纤维细胞中的一个亚型可能来源于骨髓的母细胞,即纤维细胞。本综述着重探讨与TAO发病机制相关的假设,并且提示这些观点如何指导发现新的治疗方法。

Thyroid-associated ophthalmopathy(TAO)is closely associated with Graves disease(GD),which is a common autoimmune condition.Epigenetic and environmental factors have been suggested as contributory to the development of GD and TAO.Thyroid-stimulating hormone receptor(TSHR)and insulin-1ike growth factor-1 receptor(IGF-1R)are expressed at higher levels in the orbital connective tissue from individuals with TAO than in healthy tissues.Together they form a functional complex and participate in signal transduction related to GD and TAO.Orbital fibroblasts are the target and effector cells in TAO.Recently,a subtype of the orbital fibroblasts has been putatively traced to bone marrow-derived progenitor cells,known as fibrocytes.This review highlights the putative molecular mechanisms involved in TAO and suggests how these insights provide future directions for identifying therapeutic targets.