激活的cGAS/STING信号传递在早期糖尿病视网膜病变中引起内皮细胞衰老
Haitao Liu1, Sayan Ghosh1, Tanuja Vaidya2
1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
JCI insight
|June 22, 2023
概括
干扰素基因刺激器 (STING) 在糖尿病视网膜病变 (DR) 中升高. 在糖尿病小鼠中抑制STING减少了视网膜细胞衰老,炎症和毛细血管损伤,这表明STING是DR的潜在治疗点.
科学领域:
- 眼科医生 眼科 眼科
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 糖尿病视网膜病变 (DR) 是全球视力损失的主要原因.
- 细胞衰老和炎症是DR发展和进展的关键因素.
- 干扰素基因 (STING) 刺激剂在DR病变发生中的作用尚未完全理解.
研究的目的:
- 调查STING对DR的贡献机制.
- 评估针对DR的STING治疗潜力.
主要方法:
- 在STING-KO和STING-GTimber (STINGGT) 小鼠中诱导糖尿病.
- 分析了视网膜的分子变化和病理变化.
- 评估了信号通路的关键组成部分 (TBK1,IRF3,NF-κB).
主要成果:
- 在DR患者和模型中,STING表达增加.
- 在糖尿病小鼠中,STING缺陷显著抑制了视网膜内皮细胞衰老,炎症和毛细血管退化.
- 这些保护作用与TBK1,IRF3和NF-κB的酸化减少有关.
结论:
- 刺痛在糖尿病视网膜病变的发病过程中起着至关重要的作用.
- 向STING可能为预防和治疗DR.DR.提供一种新的治疗策略.
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