Estrogen and its Receptor in Intraocular Pressure Regulation
雌激素及其受体在眼压调节中的作用
基本信息
- 批准号:10595307
- 负责人:
- 金额:$ 38.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-03-01 至 2028-02-29
- 项目状态:未结题
- 来源:
- 关键词:4-vinylcyclohexene diepoxideAffectAgeAge at MenarcheAgonistAnteriorAqueous HumorAromataseBioinformaticsCattleCell physiologyCellsChemicalsClinicClinicalCorneaDataDiseaseERR1 proteinESR1 geneEndothelial CellsEstradiolEstrogen ReceptorsEstrogen declineEstrogensExtracellular MatrixEyeEyedropsFamily suidaeFemaleFertilityGPER geneGenesGlaucomaGoalsHeterozygoteHistologyHormone replacement therapyHormone useHumanIn VitroIndividualInjectionsKnockout MiceMagnetic Resonance ImagingMechanicsMediatingMenarcheMenopauseModelingMonitorMusNG-Nitroarginine Methyl EsterNOS3 geneNerve DegenerationNerve FibersNitric OxideOcular HypertensionOral ContraceptivesOvariectomyPathogenesisPathway interactionsPatientsPeriodicityPhysiologic Intraocular PressurePhysiologicalPostmenopausePregnancyPrimary Cell CulturesPrimary Open Angle GlaucomaProductionProteinsRattusReceptor SignalingRegulationResearchResistanceRetinaRetinal DegenerationRiskRisk FactorsRoleSignal PathwaySignal TransductionStainsSteroidsStretchingStructure of sinus venosus of scleraSystemTestingThickTissuesTrabecular meshwork structureTransforming Growth Factor betaVariantVisionVisual FieldsWomanantagonist Ganterior chamberaqueouscontrast imagingeye chamberfollow-upgene networkgenetic associationgenome wide association studygenomic locushuman old age (65+)in vivoinhibitorinnovationmodifiable riskmouse modelnew therapeutic targetnovelpressureprotective effectreceptorresponsesexsingle nucleus RNA-sequencingstemtherapeutic target
项目摘要
Abstract
The goal of this application is to determine the role of estrogen and its receptors - estrogen receptor 1 (ESR1)
and G protein coupled estrogen receptor (GPER1) – in regulating intraocular pressure (IOP) through
trabecular meshwork (TM) and Schlemm's canal (SC) endothelial cells. IOP is the primary and only modifiable
risk factor for patients affected with primary open-angle glaucoma (POAG) in the clinic. TM and SC modulate
majority of aqueous humor outflow resistance in the conventional pathway. Despite the significant research
progress in TM/SC outflow dynamics, limited therapeutic targets are available for modulating the conventional
outflow. It is necessary to identify novel targets to lower IOP more efficiently in glaucoma patients with
progressive visual field loss. Several recent genome-wide association studies have identified >150 IOP-
associated genomic loci, which is too many to follow up functionally. Our comprehensive bioinformatics
analyses of these IOP-associated genomic loci indicate the enrichment of ESR1-related gene networks
among these IOP genes. Factors related with menarche, menopause, and oophorectomy have been
associated with POAG. Genetic associations have been identified between sequence variants in estrogen
receptor pathway genes and POAG. Estrogen and ESR1-related pathways including aromatase may affect
the aqueous humor outflow facility and regulate IOP levels. The presence of estradiol in aqueous humor and
ESR1 protein in the TM/SC region further supports the potential role of estrogen and ESR1-related pathways
in IOP regulation. Based on our preliminary data on the elevated IOP levels from mouse models with the loss
of Esr1 or Gper1 as well as their interaction with Nos3, we hypothesize that activation of estrogen signaling
via ESR1 and GPER1 decreases IOP and POAG risk by modulating the turnover of extracellular matrix in the
TM and the NO signaling in the SC. We propose to determine the in vivo effects of loss of estrogen signaling
via Gper1 (Aim 1) or Esr1 (Aim 2) in murine eyes using tissue-specific knockout mice, and to determine the
underlying mechanisms of Gper1 and Esr1-mediated IOP regulation using in vitro primary cell culture models
(Aim3). Successful completion of this project will help reveal the critical role of estrogen signaling in aqueous
outflow pathway and identify novel therapeutic targets to reduce IOP more effectively for this sight-threatening
disease.
摘要
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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Yutao Liu其他文献
Yutao Liu的其他文献
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{{ truncateString('Yutao Liu', 18)}}的其他基金
Cellular and Molecular Genetics of Keratoconus
圆锥角膜的细胞和分子遗传学
- 批准号:
10532398 - 财政年份:2019
- 资助金额:
$ 38.34万 - 项目类别:
Cellular and Molecular Genetics of Keratoconus
圆锥角膜的细胞和分子遗传学
- 批准号:
10398841 - 财政年份:2019
- 资助金额:
$ 38.34万 - 项目类别:
Cellular and Molecular Genetics of Keratoconus
圆锥角膜的细胞和分子遗传学
- 批准号:
10611973 - 财政年份:2019
- 资助金额:
$ 38.34万 - 项目类别:
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