Integrin Signaling in the Trabecular Meshwork
小梁网中的整合素信号传导
基本信息
- 批准号:8264354
- 负责人:
- 金额:$ 35.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-05-01 至 2014-04-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsActive SitesAffectAfrican AmericanAmino AcidsAnteriorAqueous HumorBindingBinding ProteinsBinding SitesBlindnessCell AdhesionCellsCytoplasmic TailCytoskeletonDataDown-RegulationEffectivenessEventExtracellular MatrixFibronectinsGenesGlaucomaGoalsGrantHeparinHumanIntegrin BindingIntegrin Signaling PathwayIntegrinsLaboratoriesLeadLentivirus VectorLigandsLymphocyte ActivationMolecularMonkeysMonomeric GTP-Binding ProteinsMutationOrgan Culture TechniquesPeptidesPerfusionPhysiologic Intraocular PressurePhysiologicalPlayPropertyRegulationResearchRetinal Ganglion CellsRisk FactorsRoleSignal PathwaySignal TransductionTestingTrabecular meshwork structurebasedesignpaxillinreceptortherapeutic target
项目摘要
This is a new application for a R01. The long-term objective of this grant is to identify integrin signaling
mechanisms that can be used as therapeutic targets to control and lower intraocular pressure. The glaucomas,
which lead to irreversible loss of retinal ganglion cells, affect approximately 67 million people worldwide. They
are commonly associated with elevated levels of intraocular pressure (IOP) due to a reduction in aqueous
humor outflow from the trabecular meshwork (TM). Although a number of physiological factors are known to
regulate outflow facility, one of the key factors that have emerged as an important regulatory mechanism for
outflow facility is the contractile properties of the TM. At the present, it is unclear what molecular events
regulate contractility in the TM. Studies from our laboratory have shown that the signaling properties of
bioactive fragments from the extracellular matrix (ECM) and their receptors (integrins) can be used to regulate
the contractility of the TM and increase outflow facility in cultured anterior segments. In particular we have
shown that a bioactive domain from fibronectin called the HepII domain activates a ¿4¿1 integrin signaling
pathway that decreases cell contractility in cultured TM cells. Our preliminary data strongly supports the
hypothesis that manipulation of integrin signaling pathways in the TM that modify cellular contractility can be
used to regulate outflow facility. The objective of this research is to identify possible ways to target integrin
signaling pathways in the TM in order to increase outflow facility. To this end, we propose three approaches to
activate the ¿4¿1 signaling pathway in cultured anterior segments. First, use lentiviral vectors to express a
mini-HepII gene in the TM. Second, over express a constitutively activated ¿4 integrin subunit in the TM.
Third, express peptides from the cytoplasmic domain of the ¿4-subunit or the integrin binding protein, paxillin
which disrupt cell adhesion and decrease cell contractility. The studies proposed in this application will not
only enhance our understanding of the role of integrin signaling in the TM, but it will identify new ways to target
cell contractility in the TM.
这是R01的新应用程序。这项拨款的长期目标是确定整合素信号
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Donna M Peters其他文献
Donna M Peters的其他文献
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{{ truncateString('Donna M Peters', 18)}}的其他基金
Targeting the Anterior Segment with Homing Peptides from Phage Display
使用噬菌体展示的归巢肽靶向眼前节
- 批准号:
8487758 - 财政年份:2013
- 资助金额:
$ 35.27万 - 项目类别:
Targeting the Anterior Segment with Homing Peptides from Phage Display
使用噬菌体展示的归巢肽靶向眼前节
- 批准号:
8651496 - 财政年份:2013
- 资助金额:
$ 35.27万 - 项目类别:
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