Mechanism of differential involvement of muscle groups in the retrobulbar tissue of thyroid eye disease
宋诗涵 1张曹旭 2李润钏 1张悦 2吴枫瑶 2宋怀东 2沈勤 1周慧芳 1朱梅华
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作者信息
1. 上海交通大学医学院附属第九人民医院眼科，上海 200011
2. 上海交通大学医学院附属第九人民医院内分泌科，上海 200011
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摘要
目的 甲状腺眼病患者球后组织不同部位的眼外肌受累严重程度不同，但机制不明。本研究旨在探究不同部位眼外肌中促甲状腺激素受体(thyroid stimulating hormone receptor, TSHR)表达的差异与眼外肌受累程度不同之间的关系。 方法 分离大鼠的球后组织中的内直肌、外直肌、上直肌和下直肌，通过免疫荧光和荧光定量PCR检测TSHR在4条眼外肌的表达水平。收集斜视手术患者的眼外肌组织，通过荧光检测TSHR的表达及其表达的细胞类型。 结果 荧光定量PCR结果显示，TSHR在大鼠球后组织内直肌中的表达明显高于外直肌、上直肌和下直肌(内直肌对外直肌，P＝0.012；内直肌对上直肌，P＝0.015；内直肌对下直肌，P＝0.013)，但胰岛素样生长因子1受体(insulin-like growth factor 1, IGF-1R)无差异。双色免疫荧光结果显示，TSHR与肌卫星细胞的分子标志PAX7共表达，且大鼠和人的内直肌中的表达明显高于另外三条眼外肌。 结论 TSHR在内直肌肌卫星细胞中特异性高表达，可能是甲状腺眼病内直肌最容易受累的原因。 Objective The degree of involvement of extraocular muscles varies across different regions of retrobulbar tissue in patients with thyroid eye disease, but the mechanism is unclear. This study aims to explore the relationship between differential expression of thyroid-stimulating hormone receptor(TSHR) in different parts of the extraocular muscles and the varying degrees of muscle involvement. Methods The medial, lateral, superior, and inferior rectus muscle were separated from the retrobulbar tissue of rats, and the expression level of TSHR in four extraocular muscles was detected by immunofluorescence and qPCR. Extraocular muscle tissue of patients with strabismus was collected to detect the expression of TSHR and the cell types expressed by fluorescence. Results The results of qPCR showed that the expression of TSHR in the medial rectus muscle was significantly higher than that in the lateral, superior, and inferior rectus muscle(medial rectus vs lateral rectus, P=0.012 medial rectus vs superior rectus, P=0.015 medial rectus vs inferior rectus, P=0.013), but there was no difference in insulin-like growth factor 1(IGF-1R) expression. Immunofluorescence showed that TSHR was co-expressed with PAX7, a molecular marker of muscle satellite cells, and the expression level in the medial rectus muscle of rats and humans was significantly higher than those in the other three extraocular muscles. Conclusion The high specific expression of TSHR in the satellite cells of the medial rectus muscle may be the reason why the medial rectus muscle is most susceptible to involvement in thyroid eye disease.
Abstract
Objective The degree of involvement of extraocular muscles varies across different regions of retrobulbar tissue in patients with thyroid eye disease, but the mechanism is unclear. This study aims to explore the relationship between differential expression of thyroid-stimulating hormone receptor(TSHR) in different parts of the extraocular muscles and the varying degrees of muscle involvement. Methods The medial, lateral, superior, and inferior rectus muscle were separated from the retrobulbar tissue of rats, and the expression level of TSHR in four extraocular muscles was detected by immunofluorescence and qPCR. Extraocular muscle tissue of patients with strabismus was collected to detect the expression of TSHR and the cell types expressed by fluorescence. Results The results of qPCR showed that the expression of TSHR in the medial rectus muscle was significantly higher than that in the lateral, superior, and inferior rectus muscle(medial rectus vs lateral rectus, P=0.012 medial rectus vs superior rectus, P=0.015 medial rectus vs inferior rectus, P=0.013), but there was no difference in insulin-like growth factor 1(IGF-1R) expression. Immunofluorescence showed that TSHR was co-expressed with PAX7, a molecular marker of muscle satellite cells, and the expression level in the medial rectus muscle of rats and humans was significantly higher than those in the other three extraocular muscles. Conclusion The high specific expression of TSHR in the satellite cells of the medial rectus muscle may be the reason why the medial rectus muscle is most susceptible to involvement in thyroid eye disease.
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