Broad spectrum caspase inhibitor rescues retinal ganglion cells after ischemia.

Broad spectrum caspase inhibitor rescues retinal ganglion cells after ischemia.
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广谱半胱天冬酶抑制剂可挽救缺血后的视网膜神经节细胞。

DOI:
10.1097/00001756-200404290-00010
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发表时间:
2004
期刊:
影响因子:
1.7
通讯作者:
Sharma,SansarC
Sharma,SansarC
中科院分区:
医学4区
文献类型:
--
作者:
Patil,Kiran;Sharma,SansarC

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缺血/再灌注后,成年Wistar大鼠视网膜中视网膜神经节细胞的死亡持续数周。使用新的,更稳定的半胱天冬酶抑制剂,Q-VD-OPH,我们研究了其对可识别的视网膜神经节细胞缺血75分钟后再灌注的神经保护作用。缺血再灌注48 h后玻璃体腔注射Q-VD-OPH。通过顶盖内注射荧光金标记视网膜神经节细胞,并在平板安装的视网膜上计数细胞。在Q-VD-OPH注射眼中,缺血/再灌注2周和3周后视网膜神经节细胞存活增加。我们研究了凋亡细胞死亡的免疫细胞化学标记视网膜裂解聚(ADP-核糖)聚合酶(PARP)。在缺血/再灌注1、2、3周后,神经节细胞层和内核层中裂解的PARP的标记仍然升高。Q-VD-OPH的施用显著减少了视网膜中切割的PARP的标记,并增加了视网膜神经节细胞的存活。
Following ischemia/reperfusion the death of retinal ganglion cells in adult Wistar rat retina continues for weeks. Using new, more stable caspase inhibitor, Q-VD-OPH we studied its neuroprotective effect on identifiable retinal ganglion cells after 75 min ischemia followed by reperfusion. Q-VD-OPH was injected intravitreally 48 h after ischemia/reperfusion. Retinal ganglion cells were labeled by intratectal injection of Fluorogold and cells were counted on flat mounted retinas. Retinal ganglion cells survival increased after 2 and 3 weeks of ischemia/reperfusion in Q-VD-OPH injected eyes. We studied apoptotic cell death by immunocytochemically labeling retina with cleaved Poly (ADP-ribose) polymerase (PARP). Labeling for cleaved PARP remained elevated in the ganglion cell layer and inner nuclear layer after 1, 2and 3 weeks of ischemia/reperfusion. Administration of Q-VD-OPH significantly reduced the labeling for cleaved PARP in the retina and increased the survival of retinal ganglion cells.