Platelets accumulate in the diabetic retinal vasculature following endothelial death and suppress blood-retinal barrier breakdown.
Platelets accumulate in the diabetic retinal vasculature following endothelial death and suppress blood-retinal barrier breakdown.
复制标题
内皮细胞死亡后，血小板积聚在糖尿病视网膜血管系统中，并抑制血-视网膜屏障的破坏。
DOI：
10.1016/s0002-9440(10)63648-6
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Adamis,AnthonyP
中科院分区：
文献类型：
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作者：
Yamashiro,Kenji;Tsujikawa,Akitaka;Ishida,Susumu;Usui,Tomohiko;Kaji,Yuichi;Honda,Yoshihito;Ogura,Yuichiro;Adamis,AnthonyP
血小板微血栓存在于人类和啮齿动物的糖尿病视网膜脉管系统中；然而，其存在的机制和后果尚未确定。目前的研究表明，在实验性糖尿病两周内，含有微血栓的血小板在大鼠的视网膜脉管系统中积聚，这是已知发生白细胞介导的内皮细胞损伤和死亡的时间点。血小板积累随着糖尿病病程的延长而增加，交叉实验表明，最大血小板积累需要糖尿病血小板和糖尿病内皮。血小板积累也与糖尿病视网膜中 Fas 和 FasL 的表达一致。当用抗FasL中和抗体抑制内皮细胞凋亡时，血小板聚集被有效抑制。当用抗血小板抗体从体循环中耗尽血小板时，糖尿病动物的血视网膜屏障破坏加剧。这些发现表明，糖尿病视网膜血管系统中的血小板积聚是继发于内皮细胞死亡的，并且在一定程度上起到抑制血-视网膜屏障破坏的作用。
Platelet microthrombi are present in the diabetic retinal vasculature of humans and rodents; however, the mechanisms and consequences of their presence have not been defined. The current study demonstrates that platelet containing microthrombi accumulate in the retinal vasculature of the rat within 2 weeks of experimental diabetes, a timepoint at which leukocyte-mediated endothelial cell injury and death are known to occur. Platelet accumulation increased with the duration of diabetes, and crossover experiments revealed that maximal platelet accumulation required both diabetic platelets and a diabetic endothelium. Platelet accumulation also coincided with the expression of Fas and FasL in the diabetic retina. When endothelial cell apoptosis was inhibited with an anti-FasL neutralizing antibody, platelet accumulation was effectively suppressed. When platelets were depleted from the systemic circulation with an anti-platelet antibody, blood-retinal barrier breakdown worsened in the diabetic animals. These findings suggest that platelet accumulation in the diabetic retinal vasculature is secondary to endothelial cell death and serves, in part, to suppress blood-retinal barrier breakdown.