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.
总结
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:
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.
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:
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Christopher Dale Conrady其他文献
Christopher Dale Conrady的其他文献
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