Dynamic Variable Aqueous Humor Outflow and Glaucoma Therapies in the Human Eye
人眼的动态可变房水流出和青光眼治疗
基本信息
- 批准号:10617852
- 负责人:
- 金额:$ 44.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcetylcholineAffectAngiographyAnteriorAqueous HumorAreaBehaviorBiologyBlindnessBrain DeathBypassCarbacholCell DeathCharacteristicsCiliary MuscleComplexCoupledCytoskeletonDiseaseDistalDrainage procedureDrug Delivery SystemsDrug FormulationsDrug TargetingEndothelin-1EngineeringExcisionEyeFDA approvedFutureGenomicsGlaucomaGoalsGrantHistologicHumanImageImaging DeviceIndividualInstitutional Review BoardsLaboratoriesLiquid substanceLocationMeasuresMethodsMolecularMovementMuscarinicsNational Eye InstituteNitric OxideOperating RoomsOperative Surgical ProceduresOptical Coherence TomographyOpticsOrgan DonorPathway interactionsPatient CarePatientsPatternPerfusionPharmaceutical PreparationsPharmacological TreatmentPhysiologic Intraocular PressurePhysiologicalPilocarpineProcessProteomicsProtocols documentationRegulationRelaxationResearchResearch PersonnelResourcesRetinal Ganglion CellsRho-associated kinaseRisk FactorsRouteScienceStructure of sinus venosus of scleraStudy modelsSystemTimeTrabecular meshwork structureTracerTranslatingUnited StatesUnited States National Institutes of HealthVeinsVenousVisionWorkaqueouscholinergicclinical caredrug developmentexperimental studyglaucoma surgeryhuman modelhuman tissueimprovedin vivoindividual patientinnovationkinase inhibitornovelnovel therapeuticspersonalized medicinepharmacologicreal-time imagesresponsestructural imagingsuccesstool
项目摘要
Project Summary
Glaucoma is a leading cause of permanent vision loss worldwide, and the only treatment is to lower intraocular
pressure (IOP). IOP is governed by how aqueous humor (the fluid in the eye) exits the drainage pathways that
start at the trabecular meshwork (TM) before moving into Schlemm’s canal, collector channels, an intrascleral
venous plexus, and aqueous/episcleral veins. However, recent discoveries have demonstrated that aqueous
humor outflow (AHO) is not static and unchanging but is more complex than a simple linear depiction. AHO
shows dynamic variable behavior (or dynamic variable outflow; DVO) where it is variable with segmental
regions of the eye displaying high- or low-AHO, is dynamic where AHO can spontaneously increase or
decrease in different locations of the eye, and is improvable where drugs or surgeries can enhance it. Thus,
this proposal aims to better study DVO by uncovering how and why AHO can be improved in certain regions of
the eye. This helps understand what may have been lost in disease and what may be targeted in IOP-lowering
treatments. The central hypothesis in this proposal is that glaucoma therapies work at improvable DVO
regions and that by facilitating DVO research and knowing where and how this occurs, personalized glaucoma
treatments can be crafted for individual patients. To accomplish this, we will utilize cutting edge structural
imaging tools such as anterior segment optical coherence tomography (OCT). We will also use a method
called aqueous angiography that we developed on a previous National Institutes of Health and National Eye
Institute grant. Aqueous angiography allows researchers to see exactly where aqueous humor is flowing in the
eye in a real-time fashion. With these tools, we will study ex vivo human eyes in the laboratory and in donor in
vivo eyes to yield the most germane discoveries for glaucoma and glaucoma treatment. In Specific Aim (SA1),
we will discover how DVO is regulated by studying the structural and molecular basis of segmental and
dynamic AHO using imaging and screen-based tools on human donor and ex vivo eyes in the laboratory. In
SA2, we will use ex vivo human eyes to study how glaucoma surgeries in different locations in the eye impact
IOP lowering and what hurdles the proximal vs. distal AHO pathways present to surgical success. In SA3, we
will investigate how glaucoma pharmacological drugs (currently FDA-approved drug formulations and delivery)
alter DVO in ex vivo and donor eyes, specifically looking at the parts of the eye that are improved by treatment
to understand why these areas had the capacity to do so. Through the results of this proposal, we will better
understand the dynamic processes of how intraocular fluid leaves the eye as a way to enhance current
glaucoma treatments and to create a springboard to innovate new ones.
项目摘要
青光眼是世界范围内永久性视力丧失的主要原因,唯一的治疗方法是降低眼内压。
压力(IOP)。IOP由房水(眼睛中的液体)如何离开排出通道来控制,
从小梁网(TM)开始,然后进入Schlemm管、收集通道、巩膜内
静脉丛和水/巩膜外静脉。然而,最近的发现表明,
幽默流出(AHO)不是静止不变的,而是比简单的线性描述更复杂的。AHO
显示动态变量行为(或动态变量流出量; DVO),其中它随节段变化
显示高或低AHO的眼睛区域是动态的,其中AHO可以自发地增加或
在眼睛的不同位置减少,并且在药物或手术可以增强的地方可以改善。因此,
该提案旨在通过揭示如何以及为什么可以在某些地区改进AHO,
the eye.这有助于了解疾病中可能丢失的内容以及降低IOP的目标是什么
治疗。该建议的中心假设是青光眼治疗在可改善的DVO下起作用
通过促进DVO研究并了解这种情况在哪里以及如何发生,
可以为个别患者制定治疗方案。为了实现这一目标,我们将利用先进的结构
成像工具,例如前段光学相干断层扫描(OCT)。我们还将使用一种方法
我们在之前的国立卫生研究院和国家眼科研究所的基础上开发了一种叫做水血管造影术的方法,
研究所补助金。眼房水血管造影术使研究人员能够准确地看到眼房水在眼内流动的位置。
实时的眼睛。有了这些工具,我们将在实验室和供体中研究离体人眼,
活体眼睛产生最密切的发现青光眼和青光眼治疗。在具体目标(SA 1),
我们将通过研究DVO的节段性和非节段性的结构和分子基础,
在实验室中使用成像和基于屏幕的工具对人类供体和离体眼睛进行动态AHO。在
SA 2,我们将使用离体人眼来研究青光眼手术在眼睛不同位置的影响
IOP降低以及近端与远端AHO通路对手术成功的障碍。在SA 3中,我们
将研究青光眼药理学药物(目前FDA批准的药物制剂和递送)
改变离体和供体眼睛中的DVO,特别是观察通过治疗改善的眼睛部分
来理解为什么这些地区有能力这样做。通过这次提案的结果,我们将更好地
了解眼内液体如何离开眼睛的动态过程,以增强电流
青光眼治疗,并创造一个跳板,创新新的。
项目成果
期刊论文数量(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Arm-mounted optical coherence tomography angiography in extremely low birth weight neonates with retinopathy of prematurity.
- DOI:10.1016/j.ajoc.2020.100624
- 发表时间:2020-06-01
- 期刊:
- 影响因子:0
- 作者:Kothari, Nikisha;Chu, Alison;Tsui, Irena
- 通讯作者:Tsui, Irena
Subconjunctival Lymphatics Respond to VEGFC and Anti-Metabolites in Rabbit and Mouse Eyes.
- DOI:10.1167/iovs.63.10.16
- 发表时间:2022-09-01
- 期刊:
- 影响因子:4.4
- 作者:
- 通讯作者:
Recruitment of Temporal Aqueous Outflow Channels After Bent Needle Ab-Interno Goniectomy Demonstrated by Aqueous Angiography.
房水血管造影显示弯针腹内房角切除术后颞房房水流出通道的募集。
- DOI:10.1097/ijg.0000000000002131
- 发表时间:2023
- 期刊:
- 影响因子:2
- 作者:Dada,Tanuj;Bukke,AnandNaik;Huang,AlexS;Sharma,Namrata;Verma,Saurabh
- 通讯作者:Verma,Saurabh
Indocyanine Green Aided Schlemm Canal Identification During Gonioscopic Assisted Transluminal Trabeculotomy.
- DOI:10.1097/ijg.0000000000002047
- 发表时间:2022-08-01
- 期刊:
- 影响因子:2
- 作者:
- 通讯作者:
Aqueous outflow channels and its lymphatic association: A review.
- DOI:10.1016/j.survophthal.2021.10.004
- 发表时间:2022-05
- 期刊:
- 影响因子:5.1
- 作者:Narayanaswamy, Arun;Thakur, Sahil;Nongpiur, Monisha E.;Schmetterer, Leopold;Hong, Young-Kwon;Huang, Alex S.;Wong, Tina T.
- 通讯作者:Wong, Tina T.
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{{ truncateString('Alex S Huang', 18)}}的其他基金
Dynamic Variable Aqueous Humor Outflow and Glaucoma Therapies in the Human Eye
人眼的动态可变房水流出和青光眼治疗
- 批准号:
10155489 - 财政年份:2020
- 资助金额:
$ 44.58万 - 项目类别:
Dynamic Variable Aqueous Humor Outflow and Glaucoma Therapies in the Human Eye
人眼的动态可变房水流出和青光眼治疗
- 批准号:
10405079 - 财政年份:2020
- 资助金额:
$ 44.58万 - 项目类别:
Dynamic Variable Aqueous Humor Outflow and Glaucoma Therapies in the Human Eye
人眼的动态可变房水流出和青光眼治疗
- 批准号:
10563298 - 财政年份:2020
- 资助金额:
$ 44.58万 - 项目类别:
Discovery and Characterization of Anterior Sclera Pathology in Glaucoma
青光眼前巩膜病理学的发现和表征
- 批准号:
9128004 - 财政年份:2014
- 资助金额:
$ 44.58万 - 项目类别:
Discovery and Characterization of Anterior Sclera Pathology in Glaucoma
青光眼前巩膜病理学的发现和表征
- 批准号:
8930993 - 财政年份:2014
- 资助金额:
$ 44.58万 - 项目类别:
Discovery and Characterization of Anterior Sclera Pathology in Glaucoma
青光眼前巩膜病理学的发现和表征
- 批准号:
8766162 - 财政年份:2014
- 资助金额:
$ 44.58万 - 项目类别:
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