Innate Immunity to Viral Infection of the Retina

视网膜对病毒感染的先天免疫

基本信息

项目摘要

SUMMARY Alpha herpesviruses are a subfamily of ubiquitous viruses that can cause a spectrum of clinically-significant diseases including blindness from acute retinal necrosis (ARN). Unfortunately, even with timely antiviral treatment, irreversible pathological changes occur within the retina and significantly increase the risk of vision- threatening complications to further compromise an already poor visual prognosis. Since the advent of acyclovir, there have been no major advances in the treatment of clinically-significant herpes infections despite the vision-degrading complications and very little is known in regards to the immune response to the virus within the retina. This proposal will provide a fundamental understanding of the innate immune response to HSV-1 within the retina, while developing critical skills in career development. The long-term goal of this project is to acquire the scientific skills needed to enhance our understanding and pursue novel therapies to preserve vision and reduce complications related to ARN as an independent clinician-scientist. The scientific objective of this K08 proposal is to test the hypothesis that type I interferons (IFNs) are central to host defense to viral infection of the retina and that toll-like receptor-3 within retinal microglia activate this innate immune response. We propose evaluating the innate immune response to herpes virus infections of the retina by utilizing several immune knock-out mouse lines, human retinal cell cultures, and vitreous specimens from patients with ARN to assess the role of IFNs and their role in neuroinflammation. Three focused specific aims will be utilized to test our hypothesis: 1) Identify pathways and cell types responsible for HSV innate immunity within the retina; 2) Determine the role of downstream IFNs in host defense against viral infection of the retina; 3) Identify the predominate IFN subtype and cellular source in acute retinal necrosis from human samples. The career development objective is to develop the mentorship and expertise needed to become a productive and independent clinician-scientist. The Department of Ophthalmology and Visual Sciences and the University of Nebraska Medical Center have state-of-the-art laboratory facilities and world-class faculty with expertise in neuroimmunology, viral infections, and innate immune signaling to serve as the mentoring team. The institutional resources, mentorship team, and career development plan have been developed to specifically promote scientific independence in the study of neuroinflammation of the retina.
摘要 阿尔法疱疹病毒是普遍存在的病毒的一个亚家族,可以引起一系列临床显著的 包括急性视网膜坏死(ARN)致盲在内的疾病。不幸的是,即使有及时的抗病毒药物 治疗后,视网膜内会发生不可逆转的病变,并显著增加视力风险- 可能会出现并发症,进一步危及本已很差的视力预后。自从……出现以来 阿昔洛韦,在治疗具有临床意义的疱疹感染方面没有重大进展,尽管 视力下降的并发症,对病毒的免疫反应知之甚少 在视网膜内。这一提议将提供对先天免疫反应的基本理解。 视网膜内的HSV-1病毒,同时培养职业发展中的关键技能。这样做的长期目标是 该项目是获得所需的科学技能,以提高我们的理解和追求新的治疗方法,以 作为一名独立的临床科学家,保护视力并减少与ARN相关的并发症。 这项K08提案的科学目标是测试I型干扰素(IFN)是 宿主对视网膜病毒感染和视网膜小胶质细胞内Toll样受体-3激活的中枢防御 这种先天免疫反应。我们建议评估对疱疹病毒感染的先天免疫反应。 通过利用几种免疫基因敲除的小鼠系、人视网膜细胞培养物和玻璃体 从ARN患者的样本中评估IFN的作用及其在神经炎症中的作用。三 我们将利用聚焦的特定目标来检验我们的假设:1)确定负责 视网膜内的HSV先天免疫;2)确定下游IFN在宿主防御病毒中的作用 视网膜感染;3)确定急性视网膜坏死的主要干扰素亚型和细胞来源 从人体样本中提取。 职业发展的目标是发展成为一名 多产且独立的临床医生兼科学家。眼科和视觉科学系 内布拉斯加大学医学中心拥有最先进的实验室设施和世界级的教师队伍 在神经免疫学、病毒感染和先天免疫信号方面的专业知识将作为指导团队。 机构资源、指导团队和职业发展计划已开发为 特别是促进视网膜神经炎症研究的科学独立性。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Type I Interferon Signaling Is Critical During the Innate Immune Response to HSV-1 Retinal Infection.
Utility of a nitinol stone extractor for intraocular foreign body removal.
The Host-Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment.
  • DOI:
    10.3390/microorganisms11082074
  • 发表时间:
    2023-08-12
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
    Dempsey, Michael P.;Conrady, Christopher D.
  • 通讯作者:
    Conrady, Christopher D.
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Christopher Dale Conrady其他文献

Christopher Dale Conrady的其他文献

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