Therapeutic Use of Soluble Fas Ligand Ameliorates Acute and Recurrent Herpetic Stromal Keratitis in Mice.
Therapeutic Use of Soluble Fas Ligand Ameliorates Acute and Recurrent Herpetic Stromal Keratitis in Mice.
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可溶性 Fas 配体的治疗用途可改善小鼠急性和复发性疱疹性基质角膜炎。
DOI：
10.1167/iovs.15-16588
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发表时间：
2015
影响因子：
4.4
通讯作者：
Stuart,PatrickM
中科院分区：
文献类型：
--
作者：
Rogge,Megan;Yin,Xiao-Tang;Godfrey,Lisa;Lakireddy,Priya;Potter,ChloeA;DelRosso,ChelseaR;Stuart,PatrickM
目的：本研究的目的是测试可溶性FasL（sFasL）的治疗价值在急性模型的疱疹性角膜基质炎（HSK），更重要的是，复发模型的HSK使用BALB/c，BALB-lpr，和美国国立卫生研究院（NIH）mice.Methods：小鼠感染急性与单纯疱疹病毒1型（HSV-1）的科斯株或潜伏与McKrae株HSV-1。急性感染的小鼠以及紫外线-B（UV-B）再激活的小鼠（复发性感染）用sFasL，或可溶性TNF-相关的凋亡诱导配体（sTRAIL），或BSA治疗，每天或3次/周，通过使用结膜下注射和局部软膏的组合，或与局部软膏单独使用。这些小鼠，然后进行评估角膜混浊和新生血管6 weeks.Results：急性和复发性HSV-1感染后，野生型BALB/c小鼠与sFasL治疗显示角膜混浊和新生血管的发病率显着降低相比，对照组动物。然而，如预期的，Fas+炎性细胞缺陷的BALB-1 pr小鼠在眼部疾病中没有显示出这样的差异。用sFasL治疗的潜伏感染NIH小鼠显示出类似的结果。流式细胞术分析显示，在那些与sFasL治疗的角膜炎性浸润显着低于sTRAIL或BSA治疗的小鼠。此外，从sFasL治疗的小鼠角膜显示相对更多的细胞进行apoptosis.Conclusions：这项研究提供的证据表明，sFasL治疗具有潜在的治疗益处，在减少炎症浸润和新生血管形成的原发性和复发性形式的HSK，它这样做是通过增加限制Fas+炎症细胞介导的膜FasL。
Purpose: The present study was designed to test the therapeutic value of soluble FasL (sFasL) in an acute model of herpetic stromal keratitis (HSK) and, more importantly, a recurrent model of HSK using BALB/c, BALB-lpr, and National Institutes of Health (NIH) mice.Methods: Mice were infected either acutely with the KOS strain of herpes simplex virus 1 (HSV-1) or latently with the McKrae strain of HSV-1. Acutely infected mice as well as ultraviolet-B (UV-B) reactivated mice (recurrent infection) were treated with sFasL, or soluble TNF-related apoptosis inducing ligand (sTRAIL), or BSA daily or 3 times/wk by using either a combination of subconjunctival injection and topical ointment, or with topical ointment alone. These mice then were evaluated for corneal opacity and neovascularization for 6 weeks.Results: Following acute and recurrent HSV-1 infection, wild-type BALB/c mice treated with sFasL displayed significantly reduced incidence of corneal opacity and neovascularization compared to the control animals. However, BALB-lpr mice, which are deficient in Fas+ inflammatory cells, displayed no such differences in ocular disease, as expected. Latently infected NIH mice treated with sFasL displayed similar results. Flow cytometric analysis revealed that the corneal inflammatory infiltrate in those treated with sFasL was significantly less than in sTRAIL-or BSA-treated mice. Furthermore, corneas from sFasL-treated mice displayed relatively more cells undergoing apoptosis.Conclusions: This study provides evidence that sFasL treatment has potential therapeutic benefit in reducing inflammatory infiltrate and neovascularization in primary and recurrent forms of HSK, and that it does so by augmenting the restriction of Fas+ inflammatory cells mediated by membrane FasL.