Tissue type plasminogen activator facilitates NMDA-receptor-mediated retinal apoptosis through an independent fibrinolytic cascade
Tissue type plasminogen activator facilitates NMDA-receptor-mediated retinal apoptosis through an independent fibrinolytic cascade
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DOI：
10.1167/iovs.04-0595
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发表时间：
2005-04-01
影响因子：
4.4
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
目的.探讨视网膜细胞损伤中细胞凋亡与纤溶系统的关系。使用组织型纤溶酶原激活物缺陷型（tPA（-/-））、尿激酶型纤溶酶原激活物缺陷型（uPA（-/-））、纤溶酶原激活物抑制剂-1缺陷型（派-1（-/-））、α 2抗纤溶酶缺陷型（α 2 AP（-/-））小鼠及其野生型对应物。玻璃体内注射兴奋性毒素N-甲基-D-天冬氨酸（NMDA）诱导视网膜细胞损伤。用TUNEL法检测视网膜细胞损伤情况。tPA（-/-）小鼠对由施用NMDA引起的视网膜细胞损伤具有抵抗力，并且派-1（-/-）小鼠比其野生型更受损伤。uPA（-/-）和α 2 AP（-/-）与野生型小鼠相比，差异无统计学意义。结果强烈表明，内源性tPA，而不是uPA作为一个促进剂在NMDA诱导的视网膜细胞损伤，其机制可能不与纤溶酶原裂解成纤溶酶的纤溶级联。
PURPOSE. To investigate the association between apoptosis and the fibrinolytic system in retinal cell damage.METHODS. Tissue type plasminogen activator-deficient (tPA(-/-)), urokinase type plasminogen activator-deficient (uPA(-/-)), plasminogen activator inhibitor-1-deficient (PAI-1(-/-)), alpha 2 antiplasmin-deficient (alpha 2 AP(-/-)) mice, and their wild-type counterparts were used. Retinal cell damage was induced by intravitreal injection of the excitotoxin N-methyl-D-aspartate (NMDA). The TdT-dUTP terminal nick-end labeling (TUNEL) method was used to examine retinal cell damage.RESULTS. tPA(-/-) mice were resistant to retinal cell damage caused by administration of NMDA, and PAI-1(-/-) mice were more injured than their wild-type. No significant difference was observed between uPA(-/-) or alpha 2 AP(-/-) and their wildtype mice.CONCLUSIONS. The results strongly suggest that endogenous tPA, but not uPA acts as a facilitator in NMDA-induced retinal cell damage, and that its mechanism may not be associated with cleavage of plasminogen into plasmin in the fibrinolytic cascade.