肌源性神经营养因子在急性共同性内斜视中眼外肌神经支配的相关研究
批准号:
82101174
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
郝洁
依托单位:
学科分类:
视觉、视光学与近视、弱视及眼肌疾病
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
郝洁
中文摘要
急性共同性内斜视(AACE)是一种起病急骤的特殊共同性内斜视,伴复视,发病机制尚不明确。近年发现,AACE大多无颅内和全身器质性疾病,与近距离阅读增多存在正相关性,可能与眼外肌异常神经支配有关,但缺乏分子水平的研究证据。肌源性神经营养因子中的胶质细胞源性神经营养因子(GDNF)和胰岛素样生长因子-1(IGF-1)是眼外肌发育和重塑的重要因子,参与眼外肌神经支配,影响眼外肌收缩。本课题旨在探索AACE眼外肌发生异常神经支配与GDNF和IGF-1在眼外肌短期内含量异常有关的分子生物学水平证据。拟研究(1)AACE眼外肌是否发生异常神经支配;(2)验证AACE眼外肌异常神经支配和GDNF、IGF-1含量异常相关性;(3)动物模型验证短期降低GDNF和IGF-1在眼外肌含量,是否引起眼外肌异常神经支配。本课题为探索ACCE的分子生物学证据,研发预防和治疗相关药物提供科学依据,满足急性发病人群需求。
英文摘要
Acute concomitant esotropia (AACE) is a special concomitant esotropia with a sudden onset, accompanied by diplopia, and its pathogenesis is not clear. In recent years, it has been found that most of AACE has no intracranial and systemic organic diseases, and is positively correlated with increased close reading, which may be related to abnormal innervation of extraocular muscles, but there is a lack of evidence at the molecular level. Glial cell-derived neurotrophic factor (GDNF) and insulin-like growth factor-1 (IGF-1) in muscle-derived neurotrophic factor are important factors for the development and remodeling of extraocular muscles. They are involved in the innervation of extraocular muscles, and affect the contraction of extraocular muscles. This project aims to explore the molecular biological evidence that the abnormal innervation of AACE extraocular muscles is related to the short-term abnormal content of GDNF and IGF-1 in extraocular muscles. To study (1) whether abnormal innervation of AACE extraocular muscles occurs; (2) whether the correlation exists between abnormal innervation of AACE extraocular muscles and abnormal content of GDNF and IGF-1; (3) whether short-term reduction of GDNF and IGF-1 in extraocular muscles, may cause abnormal innervation of extraocular muscles in animal models. This project provides scientific basis for exploring the molecular biology evidence of AACE prevention and therapy, and will meet the needs of AACE patients.
项目背景:急性共同性内斜视(AACE)是一种起病急骤的伴有复视的共同性内斜视,发病机制尚不明确,可能与眼外肌异常神经支配有关,但缺乏分子水平的研究证据。肌源性神经营养因子中的胶质细胞源性神经营养因子(GDNF)和胰岛素样生长因子-1(IGF-1)是眼外肌发育和重塑的重要因子,可能参与眼外肌神经支配,影响眼外肌收缩。本研究探索AACE眼外肌是否发生异常神经支配及其与GDNF和IGF-1在眼外肌短期内含量异常是否有相关性。. 主要研究内容:通过病例对照研究,验证AACE眼外肌发生异常神经支配,和眼外肌GDNF、IGF-1含量异常相关性。通过动物实验研究,短期分别降低 GDNF和IGF-1在眼外肌含量,验证外直肌是否发生异常神经支配。. 重要结果及关键数据:本研究通过病例对照研究,证实AACE患者外直肌的突触素含量显著高于对照组(p<0.001),表明神经肌肉接头数量增加,推测是由于外直肌的力量相对较弱,导致神经肌肉接头代偿性增加以试图增强外直肌力量有关。采用实时定量聚合酶链法,证实肌源性神经营养因子GDNF和IGF-1 在AACE外直肌中基因水平含量异常,采用免疫印迹法证实IGF-1在蛋白水平含量异常。Spearman相关性分析发现AACE患者的IGF-1与突触素的相关性处于统计临界值(p=0.057),推测在一定范围内,IGF-1异常升高可使AACE患者外直肌的突触素含量发生异常升高。通过大鼠实验,证实短期降低实验组眼外肌IGF-1和GDNF表达趋势,可相应降低眼外肌突触素或神经纤维丝表达或存在降低趋势。. 科学意义:本研究成果,证实了肌源性神经营养因子IGF-1对于眼外肌神经分布的正向作用,为今后通过增加IGF-1含量途径,提升眼外肌神经支配,进而加强眼外肌收缩奠定了实验基础,为今后转化研发加强眼外肌力量的精准治疗药物提供了科学依据。
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