Role of corneal neuropeptides in the pathogenesis of herpetic stromal keratitis

角膜神经肽在疱疹性基质性角膜炎发病机制中的作用

基本信息

  • 批准号:
    8035311
  • 负责人:
  • 金额:
    $ 17.76万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-04-01 至 2012-09-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Herpes simplex virus-1 (HSV-1) recurrences can cause many ocular pathologies including, immune cell mediated chronic inflammation in the corneal stroma. If left untreated, the chronic immunoinflammatory reactions in the corneal stroma can give rise to herpetic stromal keratitis (HSK); a disease that results in permanent scarring of the cornea and is a leading cause of infection induced corneal blindness in the United States. The current therapies to manage the HSK lesions have significant downsides. Therefore, investigating novel approaches to control the severity of HSK lesions are urgently needed. In this study, we will explore the role of corneal neuropeptides, substance P (SP) and vasoactive intestinal peptide (VIP), in the progression and severity of HSK lesions in a mouse model. Our long-term goal is to understand the role of neuropeptides in regulating the immunity to HSV-1 infection. Neuropeptides SP and VIP are reported to have differential roles in promoting or inhibiting the inflammation. Our pilot studies demonstrated higher amounts of SP but lower levels of VIP in the mice corneas with severe HSK lesions in comparison to those with mild HSK lesions. Therefore, we hypothesize that neuropeptides SP and VIP in the inflamed cornea regulate the progression and severity of HSK lesions. The development of HSK lesions is immune-mediated, with the involvement of pro-inflammatory cytokines (IL-1, IL-6, IL-2, IFN-3 and TNF-1), chemokines (MIP-1 and MIP-2), and immune cell types such as neutrophils and CD4 T cells. Therefore, we will test our hypothesis by demonstrating that corneal neuropeptides SP and VIP regulate the amounts of pro- and anti-inflammatory cytokines, and chemokines in HSV-1 infected corneas. We will also demonstrate that SP and VIP regulate the influx, survival and effector function of neutrophils and CD4 T cells in virus infected corneas. We anticipate that our findings will provide a novel approach to elucidate the pathogenesis of HSK and may significantly impact the management of this condition. PUBLIC HEALTH RELEVANCE: Recurrent herpes simplex virus type-1 (HSV-1) infection of the cornea results in the development of herpetic stromal keratitis (HSK), a disease that can cause permanent scarring and loss of vision. The current therapies to control HSK have significant drawbacks. In this study, we will investigate a novel approach to manage HSK in a mouse model by understanding the role of corneal neuropeptides in the progression and severity of HSK.
描述(由申请人提供):单纯疱疹病毒-1 (HSV-1)复发可引起许多眼部病变,包括角膜基质中免疫细胞介导的慢性炎症。如果不及时治疗,角膜基质中的慢性免疫炎症反应可引起疱疹性基质角膜炎(HSK);一种导致永久性角膜疤痕的疾病,在美国是感染引起角膜失明的主要原因。目前治疗HSK病变的方法有明显的缺点。因此,迫切需要研究新的方法来控制HSK病变的严重程度。在本研究中,我们将在小鼠模型中探讨角膜神经肽,P物质(SP)和血管活性肠肽(VIP)在HSK病变进展和严重程度中的作用。我们的长期目标是了解神经肽在调节对HSV-1感染的免疫中的作用。神经肽SP和VIP在促进或抑制炎症方面有不同的作用。我们的初步研究表明,与轻度HSK病变相比,严重HSK病变小鼠角膜中SP含量较高,而VIP含量较低。因此,我们假设炎症角膜中的神经肽SP和VIP调节HSK病变的进展和严重程度。HSK病变的发展是免疫介导的,涉及促炎细胞因子(IL-1、IL-6、IL-2、IFN-3和TNF-1)、趋化因子(MIP-1和MIP-2)和免疫细胞类型(如中性粒细胞和CD4 T细胞)。因此,我们将通过证明角膜神经肽SP和VIP调节HSV-1感染角膜的促炎性和抗炎细胞因子以及趋化因子的数量来验证我们的假设。我们还将证明SP和VIP在病毒感染的角膜中调节中性粒细胞和CD4 T细胞的内流、存活和效应功能。我们预期我们的发现将为阐明HSK的发病机制提供一种新的方法,并可能对这种疾病的治疗产生重大影响。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Blocking of PDL-1 interaction enhances primary and secondary CD8 T cell response to herpes simplex virus-1 infection.
  • DOI:
    10.1371/journal.pone.0039757
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Channappanavar R;Twardy BS;Suvas S
  • 通讯作者:
    Suvas S
Substance P in the corneal stroma regulates the severity of herpetic stromal keratitis lesions.
  • DOI:
    10.1167/iovs.11-8089
  • 发表时间:
    2011-11
  • 期刊:
  • 影响因子:
    4.4
  • 作者:
    Brandon S. Twardy;Rudragouda Channappanavar;S. Suvas
  • 通讯作者:
    Brandon S. Twardy;Rudragouda Channappanavar;S. Suvas
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Susmit Suvas其他文献

Susmit Suvas的其他文献

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{{ truncateString('Susmit Suvas', 18)}}的其他基金

CXCR4: A potential therapeutic target in HSK
CXCR4:HSK 的潜在治疗靶点
  • 批准号:
    10752865
  • 财政年份:
    2023
  • 资助金额:
    $ 17.76万
  • 项目类别:
Role of insulin-like growth factor binding proteins in the pathogenesis of herpes stromal keratitis.
胰岛素样生长因子结合蛋白在疱疹基质角膜炎发病机制中的作用。
  • 批准号:
    10468069
  • 财政年份:
    2020
  • 资助金额:
    $ 17.76万
  • 项目类别:
Role of insulin-like growth factor binding proteins in the pathogenesis of herpes stromal keratitis.
胰岛素样生长因子结合蛋白在疱疹基质角膜炎发病机制中的作用。
  • 批准号:
    10056782
  • 财政年份:
    2020
  • 资助金额:
    $ 17.76万
  • 项目类别:
Role of insulin-like growth factor binding proteins in the pathogenesis of herpes stromal keratitis.
胰岛素样生长因子结合蛋白在疱疹基质角膜炎发病机制中的作用。
  • 批准号:
    10219263
  • 财政年份:
    2020
  • 资助金额:
    $ 17.76万
  • 项目类别:
Role of insulin-like growth factor binding proteins in the pathogenesis of herpes stromal keratitis.
胰岛素样生长因子结合蛋白在疱疹基质角膜炎发病机制中的作用。
  • 批准号:
    10673185
  • 财政年份:
    2020
  • 资助金额:
    $ 17.76万
  • 项目类别:
Interplay between hypoxia and oxidative phosphorylation in herpes stromal keratitis
疱疹性基质角膜炎中缺氧与氧化磷酸化之间的相互作用
  • 批准号:
    10357859
  • 财政年份:
    2019
  • 资助金额:
    $ 17.76万
  • 项目类别:
Interplay between hypoxia and oxidative phosphorylation in herpes stromal keratitis
疱疹性基质角膜炎中缺氧与氧化磷酸化之间的相互作用
  • 批准号:
    10586030
  • 财政年份:
    2019
  • 资助金额:
    $ 17.76万
  • 项目类别:
Corneal neuropeptides and herpetic stromal keratitis
角膜神经肽与疱疹性基质角膜炎
  • 批准号:
    8616376
  • 财政年份:
    2013
  • 资助金额:
    $ 17.76万
  • 项目类别:
Corneal neuropeptides and herpetic stromal keratitis
角膜神经肽与疱疹性基质角膜炎
  • 批准号:
    8504248
  • 财政年份:
    2013
  • 资助金额:
    $ 17.76万
  • 项目类别:
Corneal neuropeptides and herpetic stromal keratitis
角膜神经肽与疱疹性基质角膜炎
  • 批准号:
    9248405
  • 财政年份:
    2013
  • 资助金额:
    $ 17.76万
  • 项目类别:

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