دورية أكاديمية
A specific RIP3+ subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism.
| العنوان: | A specific RIP3+ subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism. |
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| المؤلفون: | Chang He, Yan Liu, Zijing Huang, Ziqi Yang, Tian Zhou, Sheng Liu, Zhaozhe Hao, Jing Wang, Qiumin Feng, Yizhi Liu, Yihai Cao, Xialin Liu |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America; 3/16/2021, Vol. 118 Issue 11, p1-10, 10p |
| مصطلحات موضوعية: | MICROGLIA, RNA sequencing, GENES, RETINAL diseases, DELETION mutation |
| مستخلص: | Retinal neovascularization is a leading cause of severe visual loss in humans, and molecular mechanisms of microglial activation-driven angiogenesis remain unknown. Using single-cell RNA sequencing, we identified a subpopulation of microglia named sMG2, which highly expressed necroptosis-related genes Rip3 and Mlkl. Genetic and pharmacological loss of function demonstrated that hypoxia-induced microglial activation committed to necroptosis through the RIP1/RIP3-mediated pathway. Specific deletion of Rip3 gene in microglia markedly decreased retinal neovascularization. Furthermore, hypoxia induced explosive release of abundant FGF2 in microglia through RIP3-mediated necroptosis. Importantly, blocking signaling components of the microglia necropotosis-FGF2 axis largely ablated retinal angiogenesis and combination therapy with simultaneously blocking VEGF produced synergistic antiangiogenic effects. Together, our data demonstrate that targeting the microglia necroptosis axis is an antiangiogenesis therapy for retinal neovascular diseases. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: | Complementary Index |
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