Single-cell RNA sequencing reveals a landscape and targeted treatment of ferroptosis in retinal ischemia/reperfusion injury.
Single-cell RNA sequencing reveals a landscape and targeted treatment of ferroptosis in retinal ischemia/reperfusion injury.
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单细胞 RNA 测序揭示了视网膜缺血/再灌注损伤中铁死亡的概况和靶向治疗
DOI：
10.1186/s12974-022-02621-9
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发表时间：
2022-10-26
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究旨在通过单细胞RNA测序建立小鼠视网膜缺血再灌注损伤的完整细胞图谱，探讨小鼠视网膜缺血再灌注损伤的潜在机制。单细胞RNA测序法评价小鼠视网膜缺血再灌注模型的变化。通过体内和体外实验验证抑制铁下垂对视网膜缺血再灌注损伤的保护作用。缺血再灌注损伤后，视网膜细胞明显减少，伴髓细胞活化，大量血源性免疫细胞浸润。视网膜神经元细胞中的IFNG、MAPK和NFKB信号通路，以及髓细胞中的TNF信号通路，在I/R状态下引起强烈的炎症反应。此外，在上述细胞亚型中，涉及铁代谢、氧化应激和多种程序性细胞死亡途径的基因表达也发生了变化。特别是凋亡相关基因的表达和阻断可以明显减轻炎症免疫反应，提高视网膜神经节细胞的存活率。我们在单细胞水平上建立了小鼠视网膜缺血-再灌注损伤的全面图景，揭示了铁下垂在该损伤中的重要作用，靶向抑制铁下垂可有效保护视网膜结构和功能。在线版本包含补充材料，可在10.1186/s12974-022-02621-9获得。
The aim of this study was to establish a complete retinal cell atlas of ischemia–reperfusion injury by single-cell RNA sequencing, and to explore the underlying mechanism of retinal ischemia–reperfusion injury in mice. Single-cell RNA sequencing was used to evaluate changes in the mouse retinal ischemia reperfusion model. In vivo and in vitro experiments were performed to verify the protective effect of inhibiting ferroptosis in retinal ischemia–reperfusion injury. After ischemia–reperfusion injury, retinal cells were significantly reduced, accompanied by the activation of myeloid and a large amount of blood-derived immune cell infiltration. The IFNG, MAPK and NFKB signaling pathways in retinal neuronal cells, together with the TNF signaling pathway in myeloid give rise to a strong inflammatory response in the I/R state. Besides, the expression of genes implicating iron metabolism, oxidative stress and multiple programed cell death pathways have changed in cell subtypes described above. Especially the ferroptosis-related genes and blocking this process could apparently alleviate the inflammatory immune responses and enhance retinal ganglion cells survival. We established a comprehensive landscape of mouse retinal ischemia–reperfusion injury at the single-cell level, revealing the important role of ferroptosis during this injury, and targeted inhibition of ferroptosis can effectively protect retinal structure and function. The online version contains supplementary material available at 10.1186/s12974-022-02621-9.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
Dexras1是一种小的GTPase，是谷氨酸-NMDA神经毒性所必需的。
DOI：
10.1523/jneurosci.1497-12.2013
发表时间：
2013-02-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen Y;Khan RS;Cwanger A;Song Y;Steenstra C;Bang S;Cheah JH;Dunaief J;Shindler KS;Snyder SH;Kim SF
通讯作者：
Kim SF
影响因子：
32.4
作者：
Chen, WJ;Frank, ME;Wahl, SM
通讯作者：
Wahl, SM
影响因子：
3.4
作者：
Huang, Ping;Huo, Yanjiao;Zhang, Samuel S.
通讯作者：
Zhang, Samuel S.
影响因子：
3.4
作者：
Ji, Min;Sun, Qing;Guan, Huaijin
通讯作者：
Guan, Huaijin