Endogenous tissue type plasminogen activator facilitates NMDA-induced retinal damage
Endogenous tissue type plasminogen activator facilitates NMDA-induced retinal damage
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DOI：
10.1016/j.taap.2004.03.017
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发表时间：
2004-10-01
影响因子：
3.8
通讯作者：
Kozawa, O
中科院分区：
文献类型：
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作者：
Kumada, M;Niwa, M;Kozawa, O
为了研究组织型纤溶酶原激活物（WA）在视网膜损伤中的作用，采用tPA缺陷型和野生型小鼠。在本研究中使用了两种不同的视网膜神经元损伤模型。一种是兴奋毒素处理的视网膜模型，通过直接玻璃体内注射谷氨酸类似物、NMDA或红藻氨酸（KA）产生，另一种是由眼内压的瞬时升高诱导的缺血-再灌注模型。用TUNEL法检测视网膜细胞核损伤情况。与野生型相比，低剂量但非高剂量NMDA后tPA缺陷小鼠中神经节细胞层（GCL）和内核层（INL）中TUNEL阳性细胞的数量显著减少。相比之下，玻璃体内KA或短暂性缺血均未在tPA与野生型小鼠中产生视网膜损伤的显著差异。这些数据表明，tPA缺陷小鼠对玻璃体内注射NMDA引起的视网膜损伤具有抗性，并且表明tPA在兴奋性毒素，特别是NMDA诱导的视网膜细胞损伤中起作用。(C)2004年爱思唯尔公司All rights reserved.
To investigate the role of tissue plasminogen activator (WA) in retinal damage, tPA-deficient and wild-type mice were employed. Two different retinal neuron insult models were used in the present study. One is an excitotoxin-treated retinal model, created by direct intravitreal injection of glutamate analogs, NMDA or kainic acid (KA), and the other is an ischemia-reperfusion model induced by transient elevation of intraocular pressure. TdT-dUTP terminal nick-end labeling (TUNEL) method was used to examine the retinal cell nuclear damage. The number of TUNEL-positive cells in ganglion cell layer (GCL) and inner nuclear layer (INL) in tPA-deficient mice after low-, but not high-dose NMDA was significantly less compared to wild type. In contrast, neither intravitreal KA or transient ischemia produced significant difference in retinal damage in tPA vs. wild-type mice. These data show that tPA-deficient mice are resistant to retinal damage by intravitreal injection of NMDA, and indicate that tPA plays a role in the retinal cell damage induced by excitotoxins, especially NMDA. (C) 2004 Elsevier Inc. All rights reserved.