Y-27632, a Rho-associated protein kinase inhibitor, attenuates neuronal cell death after transient retinal ischemia
Y-27632, a Rho-associated protein kinase inhibitor, attenuates neuronal cell death after transient retinal ischemia
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DOI：
10.1007/s00417-007-0666-6
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发表时间：
2008-01-01
影响因子：
2.7
通讯作者：
Tanihara, Hidenobu
中科院分区：
文献类型：
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作者：
Hirata, Akira;Inatani, Masaru;Tanihara, Hidenobu
目的短暂性视网膜缺血诱导视网膜神经元细胞死亡。缺血后损伤与白细胞通过血管内皮细胞浸润到神经组织有关。目前的研究旨在调查这种损伤是否可以通过抑制 Rho/ROCK（Rho 激酶）信号来减弱，最近显示 Rho/ROCK 信号在白细胞跨内皮迁移中发挥着关键作用。方法 将 ROCK 的选择性抑制剂 Y-27632 玻璃体内注射到短暂性视网膜缺血的大鼠眼中。通过组织学分析、TUNEL 测定和视网膜神经节细胞 (RGC) 逆行标记来评估施用和不施用 Y-27632 时神经节细胞层 (GCL) 的细胞损失和内丛状层 (IPL) 的变薄。为了检查施用 Y-27632 后缺血后视网膜中白细胞浸润的减弱情况，进行了硝酸银染色和使用抗 LCA 抗体的免疫组织化学。 结果 在诱导缺血后三小时内施用 100 nmol Y-27632 时，GCL 细胞损失和 IPL 变薄显着减弱。 TUNEL 测定和 RGC 逆行标记显示，注射 Y-27632 的视网膜中凋亡细胞数量减少，RGC 数量增加。此外，使用抗 LCA 抗体进行的硝酸银染色和免疫组织化学分析表明，Y-27632 注射液可显着抑制白细胞浸润和内皮紊乱。 结论 我们的数据表明，抑制 Rho/ROCK 信号传导通过调节神经细胞中的白细胞浸润，为缺血后神经损伤提供神经保护治疗。 组织。
Purpose Transient retinal ischemia induces the death of retinal neuronal cells. Postischemic damage is associated with the infiltration of leukocytes into the neural tissue through vascular endothelia. The current study aimed to investigate whether this damage was attenuated by the inhibition of Rho/ROCK (Rho kinases) signaling, recently shown to play a critical role in the transendothelial migration of leukocytes.Methods Y-27632, a selective inhibitor of ROCK, was injected intravitreally into rat eyes with transient retinal ischemia. Cell loss of the ganglion cell layer (GCL) and thinning of the inner plexiform layer (IPL) with and without the administration of Y-27632 were evaluated by histological anaysis, TUNEL assay and retrograde labeling of retinal ganglion cells (RGCs). To examine the attenuation of leukocyte infiltration in postischemic retinas with the administration of Y-27632, silver nitrate staining and immunohistochemistry using an anti-LCA antibody were performed.Results Cell loss of the GCL and thinning of the IPL were significantly attenuated when 100 nmol Y-27632 was administered within three hours of the induction of ischemia. TUNEL assay and retrograde labeling of RGCs showed a decreased number of apoptotic cells and an increased number of RGCs in Y-27632-injected retinas. Moreover, silver nitrate staining and immunohistochemical analysis using an anti-LCA antibody showed that Y-27632 injection dramatically inhibited leukocyte infiltration and endothelial disarrangement.Conclusions Our data suggest that inhibition of Rho/ROCK signaling offers neuroprotective therapy against postischemic neural damage, by regulating leukocyte infiltration in the neural tissue.