Interleukin-18 regulates pathological intraocular neovascularization
Interleukin-18 regulates pathological intraocular neovascularization
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DOI：
10.1189/jlb.0506342
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发表时间：
2007-04-01
影响因子：
5.5
通讯作者：
Ishibashi, Tatsuro
中科院分区：
文献类型：
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作者：
Qiao, Hong;Sonoda, Koh-Hei;Ishibashi, Tatsuro
最近，促炎细胞因子IL-18已被证明在血管生成中具有作用。本研究旨在阐明其在人类早产儿视网膜病变的氧诱导视网膜病变（OIR）小鼠模型中异常新生血管（NV）中的作用。IL-18在C57 BL/6小鼠的视网膜中组成型表达，但在第7天和第12天之间暴露于75%氧气5天的小鼠中，在出生后第17天表达短暂下降。与氧处理小鼠的IL-18减少一致，血管内皮生长因子在视网膜中表达，OIR发展。到第24天，视网膜中的NV已消退至正常水平。相比之下，暴露于高氧浓度的IL-18敲除小鼠在第17天发生更严重的OIR，并且重要的是这种情况持续到第24天。这表明IL-18负调节视网膜NV。为了进一步研究这一点，我们在OIR的发展过程中向C57 BL/6小鼠施用重组IL-18，但没有发现对视网膜病变的显著抑制。然而，当在OIR恢复期给予IL-18结合蛋白以中和内源性IL-18时，OIR在第24天仍然明显。因此，我们得出结论，IL-18通过促进其消退而不是抑制其发展来调节致病性视网膜NV。这为治疗人类视网膜病变提供了一些有用的新方法。
Recently, the proinflammatory cytokine IL-18 has been shown to have a role in angiogenesis. This study aimed to elucidate its role in abnormal neovascularization (NV) in an oxygen-induced retinopathy (OIR) mouse model of the retinopathy seen in human premature newborns. IL-18 was constitutively expressed in the retina in C57BL/6 trice, but expression transiently dropped on Day 17 after birth in mice exposed to 75% oxygen for 5 days between Days 7 and 12. Coincident with the IL-18 reduction in oxygen-treated mice, vascular endothelial growth factor was expressed in the retina, and OIR developed. By Day 24, NV in the retina had regressed to normal levels. By contrast, IL-18 knockout mice, exposed to elevated oxygen concentrations, developed more severe OIR on Day 17, and it is important that this persisted until Day 24. This suggested that IL-18 negatively regulated retinal NV. To investigate this further, we administrated recombinant IL-18 to C57BL/6 mice during the development of OIR but found no significant inhibition of retinopathy. However, when IL-18-binding protein was administered during the OIR recovery phase to neutralize endogenous IL-18, OIR was still apparent on Day 24. We therefore concluded that IL-18 regulates pathogenic retinal NV by promoting its regression rather than inhibiting its development. This suggests some useful, new approaches to treating retinopathy in humans.