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In vivo modeling of autoantibody-induced optic neuritis

In vivo modeling of autoantibody-induced optic neuritis
自身抗体诱导的视神经炎的体内模型
批准号:
10429925
负责人:
Jeffrey L Bennett
金额:
$17.16万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-07-01 至 2024-06-30
关键词:
AcuteAdrenal Cortex HormonesAffectAnatomyAnimal ExperimentationAnimal ModelAnimalsAnti-Inflammatory AgentsAntibodiesAstrocytesAutoantibodiesAutoimmuneAutomobile DrivingAxonBlindnessCellsCentral Nervous System DiseasesCerebrospinal FluidCharacteristicsClinicalComplementComplement-Dependent CytotoxicityCytolysisDemyelinating DiseasesDemyelinationsDepositionDevelopmentDiseaseDisease modelDisease remissionElectrophysiology (science)ElectroretinographyEncephalomyelitisEpitopesEvaluationFrequenciesFutureGoalsHistologicHistopathologyHumanImmuneImmunoglobulin GImmunologicsInfiltrationInflammationInflammatoryInjuryInvestigationMeasurementMeasuresMediatingMethodsModelingMonitorMultiple SclerosisMyelinNerve TissueNeuraxisNeuromyelitis OpticaNeuronsOligodendrogliaOperative Surgical ProceduresOphthalmologyOptic NerveOptic Nerve InjuriesOptic NeuritisOptical Coherence TomographyOutcomePathologyPatientsPatternPhasePlasmablastProductionPrognosisRattusRecombinant AntibodyRecoveryRecurrenceResolutionResourcesRetinaRetinal Ganglion CellsRiskSclerosisSerumSeveritiesSpecificitySpinal CordStructureSubarachnoid SpaceTechniquesTestingTherapeutic StudiesTimeTimeLineTissuesTranslational ResearchValidationVision researchVisualVisual AcuityVisual evoked cortical potentialVisual system structureaquaporin 4axon injurycentral nervous system demyelinating disorderfunctional disabilityglial activationimmunopathologyimprovedin vivoin vivo Modelinjury and repairinjury recoveryinnovationmultiple sclerosis patientnoveloligodendrocyte-myelin glycoproteinpathogenic autoantibodiespreventremyelinationresponsetissue injurytissue repairtooltranslational studytranslational therapeuticstreatment responsevisual dysfunctionwater channel

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中文摘要
翻译
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英文摘要
Project Summary Vision loss from optic neuritis (ON) is a frequent consequence of autoimmune-mediated central nervous system (CNS) disorders such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein associated disease (MOGAD). The severity of vision loss, prognosis for recovery, response to therapy, and risk of recurrence varies significantly between disorders; however, our understanding of the pathophysiologic mechanisms driving these differences remain unclear. Reliable animal models that faithfully reproduce human MS-, NMOSD-, and MOGAD-specific pathology of the visual system are desperately needed to advance our understanding of disease pathobiology and advance treatment. MS, NMOSD, and MOGAD are differentiated by the production of disease-specific pathogenic autoantibodies. We hypothesize that these disease-specific autoantibodies initiate distinctive patterns of inflammatory optic nerve injury that clinically distinguish ON in MS, MNOSD and MOGAD. We intend to develop novel models of MS, NMOSD, and MOGAD ON by delivering disease-specific monoclonal recombinant antibodies (rAbs) or serum IgG into the rat retrobulbar space using a novel surgical technique. Our long-term goal is to generate transformative in vivo models of disease-specific antibody-mediated optic neuritis to advance translational research. In specific aim 1, we will measure the time course of functional impairment and inflammatory injury during the acute phase of autoantibody-driven optic neuritis. We will measure the anatomic and functional consequences of autoantibody-mediated optic neuritis in vivo using an array of tools that assess visual acuity, retinal structure, and electrophysiology. We will correlate our in vivo results to immunohistopathologic evaluations of complement deposition, myelin loss, and inflammatory cell infiltration in optic nerve tissue. In specific aim 2, we will quantify visual recovery and remyelination following autoantibody-driven optic neuritis. We will compare visual recovery and tissue repair in untreated and corticosteroid-treated animals using functional and structural measurements. These studies will further validate disease-specificity by comparing recovery in our animal ON models to those observed in their human counterparts. In vivo metrics will be correlated with measures of tissue pathology, remyelination, and axonal injury. The development and validation of these novel disease-specific models of ON will significantly advance our understanding of MS, NMOSD, and MOGAD ON pathobiology and provide an invaluable resource for future translational and therapeutic studies.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Quantitative Assessment of Subjective Symptoms and Corneal Sensitivity in Chronic Orbital Pain Patients.
慢性眼眶疼痛患者主观症状和角膜敏感性的定量评估。
DOI: 10.1097/iop.0000000000002515
发表时间: 2024
期刊: Ophthalmic plastic and reconstructive surgery
影响因子: 2
作者: [Lee,Grace, Kardon,RandyH, Nellis,JulieK, Pham,ChauM, Sales,ChristopherS, Carter,KeithD, Shriver,ErinM]
通讯作者: Shriver,ErinM
Microglial impact on remyelination
  • 批准号:
    10175074
  • 项目类别:
  • 资助金额:
    $48.74万
  • 财政年份:
    2020
  • 负责人:
    Jeffrey L Bennett
  • 依托单位:
Microglial impact on remyelination
  • 批准号:
    10357946
  • 项目类别:
  • 资助金额:
    $48.74万
  • 财政年份:
    2020
  • 负责人:
    Jeffrey L Bennett
  • 依托单位:
Microglial impact on remyelination
  • 批准号:
    10614374
  • 项目类别:
  • 资助金额:
    $48.74万
  • 财政年份:
    2020
  • 负责人:
    Jeffrey L Bennett
  • 依托单位:
Humoral Immunity, Astrocyte Injury, and Demyelination in Neuromyelitis Optica
  • 批准号:
    9898380
  • 项目类别:
  • 资助金额:
    $38.88万
  • 财政年份:
    2018
  • 负责人:
    Jeffrey L Bennett
  • 依托单位: