在增殖性视网膜病变中,Wnt信号介导病态血管生长
Jing Chen1, Andreas Stahl, Nathan M Krah
1Department of Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston MA 02115, USA.
Circulation
|October 5, 2011
概括
在视网膜病变中,Wnt信号和Claudin5对于病态视网膜新血管化至关重要. 针对这些途径可能为这种令人失明的疾病提供新的治疗方法.
科学领域:
- 眼科医生 眼科 眼科
- 血管生物学 血管生物学
- 分子信号传输的方法
背景情况:
- 缺血性增殖性视网膜病变通过促进异常的视网膜新血管化导致失明.
- 了解正常和病态血管之间的分子差异是针对性治疗的关键.
- Wnt信号突变与视网膜血管系统缺陷有关.
研究的目的:
- 研究Wnt信号在视网膜病变中的病态视网膜血管生长中的作用.
- 确定Wnt受体和下游分子在新血管化中的功能.
- 探索claudin5在Wnt通路驱动的血管生成中的参与.
主要方法:
- 利用氧气诱导的增殖性视网膜病变的小鼠模型.
- 评估了Wnt受体表达和在病理性新血管化中的活性.
- 研究了LRp5和dishevelled2损失对视网膜血管生长的影响.
- 在体外和体内研究了claudin5在内皮细胞发芽和血管发育中的作用.
主要成果:
- 在病理性新血管化中,Wnt受体 (Frizzled4,Lrp5) 和活性升高.
- 损失Lrp5和dishevelled2减少了病理性的新血管化.
- Lrp5 缺乏会损害视网膜血管生成和血视网膜屏障的形成,降低克劳丁5.5 的调节.
- 克劳丁5抑制抑制了Wnt驱动的内皮细胞生长和血管生长.
结论:
- 在视网膜病变中,Wnt信号在病态血管发育中起着重要作用.
- 克劳丁5在促进血管生成方面具有新的功能.
- 这些发现突出了视网膜病变的潜在治疗点.
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