Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Curr Opin Endocrinol Diabetes Obes. 2024 Oct 1;31(5):177-183. doi: 10.1097/MED.0000000000000878. Epub 2024 Jul 31.
Evolving understanding of thyroid eye disease (TED) has led to rapidly advancing therapeutic options. Most new treatments under development or recently available to patients are predicated on insights into disease mechanism.
TED, a disfiguring process, involves inflammation and remodeling of the connective tissues around the eye. TED most frequently presents as a component of Graves' disease. Advances in our understanding of cells involved in TED and their molecular interactions have led to novel therapeutic targets. Among these cell types are orbital fibroblasts and a subset comprising monocyte progenitor cells, known as CD34 + CXCR4 + fibrocytes. Among the attributes of fibrocytes is their expression of several autoantigens associated with Graves' disease, including TSHR, thyroglobulin and thyroperoxidase. Fibrocytes also express high levels of the insulin-like growth factor-I (IGF-I) receptor, thought to mediate fibroblast activation. Therapeutically targeting the TSHR/IGF-IR receptor complex using an IGF-I receptor antagonist, teprotumumab, has resulted in substantial clinical benefit for patients with TED. The neural axon repellent, Slit2, and its cognate receptor, ROBO1, appear to modulate the inflammatory phenotype of these orbit-infiltrating fibrocytes.
More detailed understanding of orbital fibroblasts and the distinctions between cell subsets comprising them should lead to more effective therapies with fewer side effects.
甲状腺眼病（TED）认识的不断发展导致治疗选择迅速发展。大多数正在开发或最近可供患者使用的新治疗方法都是基于对疾病机制的深入了解。
TED 是一种使人毁容的疾病，涉及眼睛周围结缔组织的炎症和重塑。TED 最常作为格雷夫斯病的一个组成部分出现。我们对参与 TED 的细胞及其分子相互作用的理解的进步为新的治疗靶点提供了依据。这些细胞类型包括眼眶成纤维细胞和一组由单核细胞祖细胞组成的细胞，称为 CD34+CXCR4+纤维细胞。纤维细胞的特征之一是它们表达几种与格雷夫斯病相关的自身抗原，包括 TSHR、甲状腺球蛋白和甲状腺过氧化物酶。纤维细胞还表达高水平的胰岛素样生长因子-I（IGF-I）受体，被认为介导成纤维细胞激活。使用 IGF-I 受体拮抗剂 teprotumumab 靶向 TSHR/IGF-IR 受体复合物已为 TED 患者带来了显著的临床获益。神经轴突排斥物 Slit2 及其同源受体 ROBO1 似乎调节这些眼眶浸润纤维细胞的炎症表型。
对眼眶成纤维细胞及其组成细胞亚群的更详细了解应导致副作用更少的更有效治疗方法。
