Hypothalamic Control of IOP, ICP, and the Translaminar Pressure Gradient
下丘脑对 IOP、ICP 和层压梯度的控制
基本信息
- 批准号:8894005
- 负责人:
- 金额:$ 21.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-30 至 2016-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdrenal Cortex HormonesAnimal ModelAnimalsAqueous HumorAreaAttenuatedBehaviorBicucullineBlindnessBrainCell DeathCell NucleusChemical StimulationCircadian RhythmsClinicalControl LocusDataDiseaseDisease ProgressionEnsureEyeFellowshipGlaucomaGoalsHealthHeart RateHourHumanHypothalamic structureIntracranial PressureLaboratoriesLaboratory FindingLearningMammalsMeasurementMediatingMentorsMethodsModelingMolecular Biology TechniquesNeuraxisNeurobiologyNeuronsNeurotransmittersOptic NervePathogenesisPathway interactionsPatientsPhysiologic Intraocular PressurePhysiologicalPlayProductionProteinsRNARattusReportingResearchResearch Project GrantsRetinal Ganglion CellsRisk FactorsRodentRoleScientistSleepSmall Interfering RNASpecialistSystemTechniquesThird ventricle structureTimeTrainingTranslatingVariantVenous Pressure levelWorkaqueous humor flowcareercareer developmentfeedinghypocretinin vivoinnovationmind controlneurophysiologynovelprepro-orexinpressureprogramsreceptorsuprachiasmatic nucleus
项目摘要
DESCRIPTION (provided by applicant): Glaucoma is one of the leading causes of blindness worldwide, yet we are still trying to develop a fundamental understanding of the mechanisms that cause retinal ganglion cell death. Intraocular pressure (IOP) fluctuation has recently been identified as a risk factor for glaucoma progression. There is ample evidence demonstrating that IOP varies in a cyclical manner over a 24-hour period in both human and rodents, with the peak pressure occurring in the morning hours upon awakening. Further, decreases in intracranial pressure (ICP), with postulated increases in the translaminar pressure gradient across the lamina cribrosa, has been reported in glaucoma patients. The PI recently identified that chemical stimulation of dorsomedial and perifornical hypothalamic neurons with bicuculline methoidide (BMI; 30pmol/75nl) evokes substantial increases in IOP, ICP, and the translaminar pressure gradient in the rat model. Because DMH/PeF neurons receive direct and indirect projections from the suprachiasmatic nucleus, his laboratory has hypothesized that the DMH/PeF neurons may be a key effector pathway for circadian fluctuation of IOP and control of the translaminar pressure gradient. The PI is a fellowship trained glaucoma specialist and clinician-scientist with graduate training in neurobiology. Under this mechanism, the PI proposes a mentored clinical-scientist research career development program that will provide him with additional training to help characterize this model and identify potential neurotransmitters involved in the IOP and ICP changes. Specific Aim #1 will include training in fluorophotometric analysis of aqueous humor production and in vivo recording of outflow facility immediately following chemical stimulation of the DMH/PeF neurons. Specific Aim #2 will focus on the incorporation of animal models of glaucoma into his current research and learning key molecular biology techniques that will help identify potential neurotransmitters involved in hypothalamically mediated increases in IOP and ICP following chemical stimulation of the DMH/PeF region. The results of this research will advance our understanding of the neurophysiology mediating fluctuations in IOP and shifts in the translaminar pressure gradient. We anticipate that further defining this pathway and the neurotransmitters involved will provide targets for novel glaucoma therapies aimed at reducing IOP fluctuations.
描述(由申请人提供):青光眼是全球失明的主要原因之一,但我们仍在尝试对导致视网膜神经节细胞死亡的机制发展基本理解。眼内压(IOP)波动最近被确定为青光眼进展的危险因素。有足够的证据表明,在人和啮齿动物的24小时内,IOP在24小时内以周期性的方式变化,醒来后的早晨,峰值压力发生。此外,据报道,在青光眼患者中据报道,颅内压(ICP)的降低,遍布整个lamina cribrosa的译者压力梯度的增加。 PI最近确定,用双瓜氨酸甲基甲基(BMI; BMI; 30 PMOL/75NL)刺激背侧和肌脱丘脑神经元的化学刺激会引起IOP,ICP和RAT型Translaminar压力梯度的大幅度增加。由于DMH/PEF神经元从上部核中接收直接和间接的投影,因此他的实验室假设DMH/PEF神经元可能是IOP昼夜节律波动和转换压力梯度的控制的关键效应途径。 PI是奖学金训练的青光眼专家和临床医生,并获得了神经生物学研究生培训。在这种机制下,PI提出了一项指导的临床科学家研究职业发展计划,该计划将为他提供其他培训,以帮助表征该模型并确定与IOP和ICP变化有关的潜在神经递质。具体的目标#1将包括对DMH/PEF神经元化学刺激后立即对水性幽默产生和流出设施的体内记录进行荧光测量分析的训练。具体目标#2将集中于将青光眼的动物模型纳入他当前的研究和学习关键分子生物学技术,这些技术将有助于确定与下丘脑介导的DMH/PEF区域化学刺激后,IOP和ICP涉及的潜在神经递质增加了IOP和ICP。这项研究的结果将提高我们对IOP中介导的神经生理学介导的理解,并在译者压力梯度中转移。我们预计,进一步定义这一途径和涉及的神经递质将为旨在减少IOP波动的新型青光眼疗法提供靶标。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Brian Christopher Samuels其他文献
Brian Christopher Samuels的其他文献
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{{ truncateString('Brian Christopher Samuels', 18)}}的其他基金
Central Nervous System Control of Intraocular and Intracranial Pressure
中枢神经系统控制眼内压和颅内压
- 批准号:
10090467 - 财政年份:2017
- 资助金额:
$ 21.09万 - 项目类别:
Central Nervous System Control of Intraocular and Intracranial Pressure
中枢神经系统控制眼内压和颅内压
- 批准号:
9215051 - 财政年份:2017
- 资助金额:
$ 21.09万 - 项目类别:
Hypothalamic Control of IOP, ICP, and the Translaminar Pressure Gradient
下丘脑对 IOP、ICP 和层压梯度的控制
- 批准号:
8733702 - 财政年份:2013
- 资助金额:
$ 21.09万 - 项目类别:
Hypothalamic Control of IOP, ICP, and the Translaminar Pressure Gradient
下丘脑对 IOP、ICP 和层压梯度的控制
- 批准号:
8565726 - 财政年份:2013
- 资助金额:
$ 21.09万 - 项目类别:
Hypothalamic Control of IOP, ICP, and the Translaminar Pressure Gradient
下丘脑对 IOP、ICP 和层压梯度的控制
- 批准号:
9119119 - 财政年份:2013
- 资助金额:
$ 21.09万 - 项目类别:
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