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The Mechanical Basis of Primary Open Angle Glaucoma

The Mechanical Basis of Primary Open Angle Glaucoma
原发性开角型青光眼的力学基础
批准号：
7941709
负责人：
MARK JOHNSON
金额：
$78.99万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
项目状态：
已结题
起止时间：
2009-09-30 至 2014-09-29
来源：
https://reporter.nih.gov/project-details/7941709
关键词：
AccountingAddressAdhesionsAffectAnteriorApicalApplications GrantsAqueous HumorArchitectureAreaAtomic Force MicroscopyBasement membraneBehaviorBiochemicalBiological AssayBiomechanicsBiomedical EngineeringBiophysicsCell membraneCell physiologyCell-Matrix JunctionCellsCellular biologyChairpersonCharacteristicsComputer SimulationConnective TissueConnective Tissue CellsCytometryCytoskeletonDataDiseaseDisease ProgressionDropsElementsEndothelial CellsEndotheliumEventExtracellular MatrixEyeGelGlaucomaGoalsHealthHumanIn SituIn VitroInvestigationLateralLifeLiquid substanceLiteratureMagnetismMapsMeasuresMechanicsMediatingMediator of activation proteinMedical ResearchMethodsModelingMolecularMolecular BiologyOcular HypertensionOphthalmologyOptic NerveOrgan Culture TechniquesOutcomePathogenesisPathologyPathway interactionsPerfusionPermeabilityPharmaceutical PreparationsPhysiologic Intraocular PressurePhysiologicalPhysiologyPlayPorosityPrimary Cell CulturesPrimary Open Angle GlaucomaProcessPropertyRegulationRelaxationResearchResearch DesignResearch PersonnelResistanceRoleRouteScientistSignal TransductionSiteStressStretchingStructure of sinus venosus of scleraStructure of thyroid parafollicular cellSystemTestingTimeTissuesTrabecular meshwork structureTractionUniversitiesVacuoleWorkanterior chamberaqueousbasedensityexperiencein vivomultidisciplinarynovelpressureprogramspublic health relevanceresearch studyresponsetherapeutic targettool

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DESCRIPTION (provided by applicant): The cause of the elevated aqueous humor outflow resistance associated with primary open angle glaucoma (POAG) is unknown. Studies aimed at determining the locus of this resistance in both normal and POAG eyes indicate that the bulk of outflow resistance occurs in the immediate vicinity of the inner wall endothelium of Schlemm's canal (SC). Pores found in the inner wall endothelial cells (SC cells) appear important in fluid transport across this endothelium. Our group and others have found that there is a significant reduction of inner wall pore density in POAG eyes. It is likely that these pores are formed in response to cell deformation resulting from the transcellular pressure drop across the inner wall endothelium. If SC cells were to become stiffer, then fewer pores might be expected to form, presumably leading to elevated outflow resistance. Accordingly, we hypothesize that the ocular hypertension characteristic of POAG results from an intro, including magnetic twisting cytometry (MTC), atomic force microscopy (AFM), and a unique embodiment of traction force microscopy called cell mapping rheometry. These studies will allow us to evaluate the stiffness of these cells and the traction forces they can generate. Second, we will investigate the behavior of SC cells on a stretchable gel substrate, and in a microporous filter perfusion system that allows us to grow these cells on a filter and perfuse them in a basal to apical direction (the physiological direction). These studies will examine how SC cells respond to mechanical distension. Third, our studies will focus on the biomechanics of pore formation in these cells and how this process is modulated by SC cell stiffness in enucleated human eyes and in an organ culture system. Fourth, to test the hypothesis that mediators of outflow resistance exert their effects through mechanical events involving changes in SC cell deformation and pore formation, we will use a finite riments, we will compare the biomechanical behavior of normal C cells to those of glaucomatous SC cells. Together, these aims will allow us to definitively determine whether increased stiffness of SC cells leads to a decreased inner wall porosity and consequently the increased outflow resistance characteristic of most cases of POAG. PUBLIC HEALTH RELEVANCE: Most treatments for glaucoma focus on altering the rate of aqueous humor formation or altering the path of aqueous humor outflow, but do not target the diseased tissue responsible for the elevated intraocular pressure characteristic of most cases of glaucoma. These treatments often slow the progression of the disease at the optic nerve, but frequently do not stop it. If we can determine the cause of the elevated pressure, then we may be able to develop a more effective pressure-lowering treatment or cure for this debilitating disease.
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  • 财政年份：
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  • 负责人：
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  • 依托单位：
    NORTHWESTERN UNIVERSITY
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  • 财政年份：
    2022
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  • 依托单位：
    NORTHWESTERN UNIVERSITY
The Mechanical Basis of Primary Open Angle Glaucoma
  • 批准号：
    7698588
  • 项目类别：
  • 资助金额：
    $71.56万
  • 财政年份：
    2009
  • 负责人：
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  • 依托单位：
    NORTHWESTERN UNIVERSITY
The Mechanical Basis of Primary Open Angle Glaucoma
  • 批准号：
    8136021
  • 项目类别：
  • 资助金额：
    $78.66万
  • 财政年份：
    2009
  • 负责人：
    MARK JOHNSON
  • 依托单位：
    NORTHWESTERN UNIVERSITY
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