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
- 批准号:10641586
- 负责人:
- 金额:$ 23.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:Acute DiseaseAcute Retinal Necrosis SyndromeAcyclovirAutomobile DrivingBiopsyBlindnessBrainCell Culture TechniquesCellsCentral Nervous System InfectionsCessation of lifeChimera organismChronic DiseaseClinical TreatmentCorneaDataDevelopmentDevelopment PlansDiseaseFacultyFamilyFunctional disorderFutureGoalsHerpesviridaeHerpesviridae InfectionsHerpesvirus 1HistopathologyHost DefenseHumanIFNAR1 geneImageImmuneImmune responseImmune signalingImmunityInfectionInflammationInflammatoryInnate Immune ResponseInstitutionInterferon Type IInterferonsInvestigationKnockout MiceLeucocytic infiltrateMedical centerMeningoencephalitisMentorsMentorshipMicrogliaMolecularMusNatural ImmunityNebraskaNecrosis InductionNeurocognitiveOphthalmologyOutcomePathologicPathologyPathway interactionsPatientsPrimary InfectionProductionProductivityPrognosisQuality of lifeResearchResearch PersonnelResourcesRetinaRetinal DetachmentRetinal DiseasesRetinitisRiskRoleSamplingScientistSignal TransductionSimplexvirusSourceSpecimenTLR3 geneTestingTherapeuticTissuesToll-like receptorsUniversitiesViralVirusVirus ActivationVirus DiseasesVirus ReplicationVisionVisualVisual impairmentWild Type Mousecareer developmentcell typechemokineclinically significantcytokinefundus imagingglial activationhuman tissueimprovedin vivoinsightlaboratory facilitymouse modelneuroimmunologyneuroinflammationnovelnovel therapeuticspreservationprogramsresponseretinal damagesensorskillstype I interferon receptorvaginal mucosavision science
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.
- DOI:10.1167/iovs.63.13.28
- 发表时间:2022-12-01
- 期刊:
- 影响因子:4.4
- 作者:
- 通讯作者:
Utility of a nitinol stone extractor for intraocular foreign body removal.
- DOI:10.1016/j.ajoc.2023.101917
- 发表时间:2023-12
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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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