Hyperglycemia Induces Neutrophil Extracellular Traps Formation Through an NADPH Oxidase-Dependent Pathway in Diabetic Retinopathy
Hyperglycemia Induces Neutrophil Extracellular Traps Formation Through an NADPH Oxidase-Dependent Pathway in Diabetic Retinopathy
复制标题
高血糖通过糖尿病视网膜病变中 NADPH 氧化酶依赖性途径诱导中性粒细胞胞外陷阱形成
DOI：
10.3389/fimmu.2018.03076
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发表时间：
2019-01-08
影响因子：
7.3
通讯作者：
Zhang, Xuedong
中科院分区：
文献类型：
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作者：
Wang, Luoziyi;Zhou, Xin;Zhang, Xuedong
NETosis的产物神经细胞外陷阱（NETs）在免疫反应中定位病原体和晶体。最近的研究发现，过量的NET会导致糖尿病及其并发症，如糖尿病视网膜病变（DR）。然而，NET与高血糖或DR之间的相关性仍不清楚。我们发现糖尿病患者血清中NETs水平显著升高，尤其是增殖型糖尿病视网膜病变（PDR）患者。随着时间的延长，高糖显著增加糖尿病患者NETs的产生。NADPH氧化酶的激活参与了高糖引发的NETs过程。此外，我们证实了中性粒细胞在糖尿病大鼠模型的眼睛和血管内皮细胞粘附的浸润。在糖尿病患者的玻璃体和视网膜中观察到NETs的形成，这表明NETs可能在糖尿病视网膜病变的发病机制中起作用。此外，抗VEGF治疗下调NET的产生，表明NADPH氧化酶衍生的ROS可能是抗VEGF治疗中涉及的另一种信号传导途径。
Neutrophil extracellular traps (NETs), the product of NETosis, is found to localize pathogens and crystals in immune response. Recent studies have found that excessive NETs lead to disease conditions such as diabetes and its complications like diabetic retinopathy (DR). However, the correlation between NETs and high glucose or DR remains unclear. Here, we found NETs level was significantly increased in the serum of diabetic patients, especially in proliferation diabetic retinopathy (PDR) patients. High glucose dramatically increased NETs production in diabetic individuals with time prolonging. The activation of NADPH oxidase was involved in the NETs process which is triggered by high glucose. Moreover, we verified the infiltration of neutrophils in the eyes and adhesion to vascular endothelial cells in diabetic rat models. NETs formation was observed in the vitreous bodies and retinas of diabetic individuals, which indicates NETs may play a role in the pathogenesis of diabetic retinopathy. Furthermore, anti-VEGF therapy downregulates NETs production indicating that NADPH oxidase-derived ROS may be another signaling pathway involved in anti-VEGF therapy.