Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo.

Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo.
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DOI:
10.1016/j.exer.2010.06.017
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发表时间:
2010-09
影响因子:
3.4
通讯作者:
Mitchell, Claire H.
Mitchell, Claire H.
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Huiling;Lu, Wennan;Zhang, Mei;Zhang, Xiulan;Argall, Arthur J.;Patel, Shaun;Lee, Ga Eun;Kim, Yong-Chul;Jacobson, Kenneth A.;Laties, Alan M.;Mitchell, Claire H.

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P2 X7受体与许多细胞类型的死亡有关,越来越多的证据支持它存在于神经元上。分离的视网膜神经节细胞上的P2 X7受体的激活增加细胞内钙水平并且可以杀死细胞。然而,在完整的眼睛内,神经节细胞周围的神经胶质细胞和其他细胞类型可以提供保护并减弱受体刺激的作用。因此,这项研究询问P2 X7受体的刺激是否真的可以在体内杀死视网膜神经节细胞。将药物玻璃体内注射到Long Evans大鼠的上级/鼻区域中。通过计数用氨基己烯脒标记的剩余神经节细胞的数量来确定细胞存活。与注射盐水溶液的眼睛相比,P2 X7受体激动剂BzATP降低了神经节细胞存活率。通过共注射P2 X7拮抗剂Brilliant Blue G和MRS 2540抑制神经节细胞死亡。腺苷A3腺苷受体激动剂MRS 3558也可防止P2 X7受体激活后神经节细胞的损失。总之,P2 X7受体的刺激可以在体内杀死视网膜神经节细胞。在分离的神经节细胞中鉴定的A3活化的神经保护作用在体内也是受体明显的。这意味着细胞外ATP和其保护性代谢产物腺苷之间的平衡可以影响活眼中神经节细胞的存活。
The P2X7 receptor is associated with the death of many cell types, and growing evidence supports its presence on neurons. Activation of the P2X7 receptor on isolated retinal ganglion cells increases intracellular calcium levels and can kill the cells. Within the intact eye, however, glia and other cell types surrounding the ganglion cells may provide protection and attenuate the effects of receptor stimulation. This investigation thus asks whether stimulation of the P2X7 receptor can actually kill retinal ganglion cells in vivo. Drugs were injected intravitreally into the superior/nasal region of Long Evans rats. Cell survival was determined by counting the number of remaining ganglion cells labeled with aminostilbamidine. The P2X7 receptor agonist BzATP reduced ganglion cell survival as compared to eyes injected with saline solution. Ganglion cell death was inhibited by co-injection of the P2X7 antagonists Brilliant Blue G and MRS 2540. The loss of ganglion cells following activation of the P2X7 receptor was also prevented by the adenosine A3 adenosine receptor agonist MRS 3558. In conclusion, stimulation of the P2X7 receptor can kill retinal ganglion cells in vivo. The neuroprotective effects of A3 activation identified in isolated ganglion cells are also receptor apparent in vivo. This implies that the balance between extracellular ATP and its protective metabolite adenosine can influence ganglion cell survival in the living eye.
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