Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model.
Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model.
复制标题
DOI：
10.1002/jnr.22314
复制
发表时间：
2010-05-15
影响因子：
4.2
通讯作者：
Savitz SI
中科院分区：
文献类型：
--
作者：
Rosenbaum DM;Degterev A;David J;Rosenbaum PS;Roth S;Grotta JC;Cuny GD;Yuan J;Savitz SI
坏死性凋亡是由死亡受体信号传导引发的程序性坏死。我们研究了坏死性凋亡是否会导致视网膜缺血模型中的神经元损伤和功能损伤。方法：使 Sprague-Dawley 大鼠眼压升高 45 分钟，并接受玻璃体内注射特异性坏死性凋亡抑制剂 Nec-1、其无活性类似物 (Nec-1i) 或载体。缺血7天后，进行ERG检查，然后摘除眼睛进行组织学分析。在其他动物中，对视网膜进行碘化丙啶、TUNEL 染色或蛋白质印迹，并用抗 LC-3 抗体进行探测。结果：视网膜缺血导致内层选择性神经元变性。与媒介物处理的对照组相比，Nec-1 预处理可显着保留内视网膜的厚度和组织结构，并改善功能。 Nec-1i 预处理未提供组织学或功能保护。与缺血载体对照相比，Nec-1 后处理也显着减弱了 ERG b 波的减少。 Nec-1对缺血视网膜中caspase或TUNEL标记细胞的数量没有影响，但抑制缺血后LC-3 II的诱导并减少PI标记细胞的数量。结论：坏死性凋亡是神经元细胞死亡的重要模式，并涉及视网膜缺血模型中的自噬。
Necroptosis is programmed necrosis triggered by death receptor signaling. We investigated whether necroptosis contributes to neuronal damage and functional impairment in a model of retinal ischemia. Methods: Sprague-Dawley rats were subjected to raised intraocular pressure for 45 min and received intravitreal injections of the specific necroptosis inhibitor, Nec-1, its inactive analogue (Nec-1i) or vehicle. Seven days after ischemia, ERGs were performed and then the eyes were enucleated for histological analysis. In other animals, retinas were subjected to propodium iodide, TUNEL staining or Western Blotting and probed with anti-LC-3 antibody. Results: Retinal ischemia resulted in selective neuronal degeneration of the inner layers. Pretreatment with Nec-1 led to significant preservation in thickness and histoarchitecture of the inner retina and functional improvement compared with vehicle-treated controls. Pretreatment with Nec-1i did not provide histological or functional protection. Post-treatment with Nec-1 also significantly attenuated the ERG b-wave reduction compared with ischemic vehicle controls. Nec-1 had no effect on the number of caspase or TUNEL-labelled cells in the ischemic retina but did inhibit the induction of LC-3 II and reduced the number of PI-labelled cells after ischemia. Conclusion: Necroptosis is an important mode of neuronal cell death and involves autophagy in a model of retinal ischemia.
登录
查看更多内容
影响因子：
4.7
作者：
Singh, M;Savitz, SI;Rosenbaum, DM
通讯作者：
Rosenbaum, DM
影响因子：
4.4
作者：
Berger, Samuel;Savitz, Sean I.;Rosenbaum, Daniel M.
通讯作者：
Rosenbaum, Daniel M.
影响因子：
14.8
作者：
Degterev, Alexei;Hitomi, Junichi;Yuan, Junying
通讯作者：
Yuan, Junying
影响因子：
5.3
作者：
Nakazawa, Toru;Nakazawa, Chifuyu;Benowitz, Larry I.
通讯作者：
Benowitz, Larry I.
影响因子：
14.8
作者：
Degterev, A;Huang, ZH;Yuan, JY
通讯作者：
Yuan, JY