西格玛1受体的激活在视神经受伤后保持视觉功能
Jing Wang1,2, Zhimin Xu2,3, Ruth Caldwell1,2,3
1Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia, United States.
Investigative ophthalmology & visual science
|July 7, 2025
概括
在视神经受伤后激活西格玛1受体 (Sig1R) 可以保持视力. 这种伤害后治疗可以增强视觉功能,并通过减少神经退行和炎症来保护视网膜质细胞 (RGCs).
科学领域:
- 眼科医生 眼科 眼科
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 在之前的研究中,Sigma 1受体 (Sig1R) 激活显示了视觉神经受伤后视网膜质细胞 (RGC) 的神经保护作用.
- 现有的研究主要集中在伤害前的Sig1R激活,使伤害后治疗的有效性未被探索.
研究的目的:
- 研究受伤后Sig1R激活在视神经损伤后维护视觉功能的治疗潜力.
- 为了确定在视神经受伤 (ONC) 后使用Sig1R激动剂是否可以减轻视力丧失和RGC退化.
主要方法:
- 小鼠经历了视神经粉碎 (ONC) 损伤,每天给予 (+) -pentazocine ((+) -PTZ),一个Sig1R激动剂,从损伤后6小时开始.
- 视觉功能 (敏度,对比度敏感性,PERG,VEP) 被评估,以及视网膜结构,血管,RGC存活率,质激活 (GFAP),氧化应激 (DHE) 和基因表达 (抗氧化剂/炎症途径).
主要成果:
- 在ONC小鼠中,受伤后 (+) -PTZ治疗显著保留了视力敏度,对比度敏感性,PERG和VEP反应.
- Sig1R激活限制了ONC诱导的神经退行和质激活,通过改善视网膜厚度和血管系统证明了这一点.
- 治疗上调抗氧化基因 (Nrf2,HO-1,NQO1) 和下调炎症标志物 (IL1β,TNFα,iNOS),这表明作用的双重机制.
结论:
- 用 (+) -PTZ激活Sig1R作为受伤后的干预,是维护视觉神经损伤后视觉功能的一种可行的策略.
- 这种方法为涉及视神经损伤和视力丧失的疾病提供了一个有希望的治疗途径.
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