Blood outer retina barrier regulation
Blood outer retina barrier regulation
批准号:
10329927
负责人:
DOUGLAS Chase DEAN
金额:
$57.74万
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
项目状态:
未结题
起止时间:
2020-02-01 至 2025-01-31
关键词:
Adaptor Signaling ProteinAgeAnimal ModelApicalArrestinsAutomobile DrivingBackBindingBirthBloodBlood CirculationCell DeathCellsChoroidClathrinComplexConeCytoplasmCytoskeletal ModelingDNADark AdaptationDevelopmentDiseaseDisease ProgressionDown-RegulationEndocytosisEnvironmentEpigenetic ProcessEpithelial CellsEventFaceFamilyFamily suidaeFeedbackFeedsGLUT 4 proteinGene ExpressionGenesGlucoseGlucose TransporterHypoglycemiaInjectionsInsulinIntegrinsInvestigationLabelLightLinkLipidsMalignant NeoplasmsMass Spectrum AnalysisMetabolicMetabolic PathwayMetabolismModelingMusMutationNeuronsNutrientPathway interactionsPeripheralPhagocytosisPhosphatidylserinesPhosphorylationPhotoreceptorsProteinsReadingRegulationResolutionRetinaRetinal PigmentsRetinitis PigmentosaRodRod Outer SegmentsSignal PathwaySignal TransductionStarvationStructure of retinal pigment epitheliumSurfaceTXNIP geneTimeTransplantationVisionVisualWorkalpha ketoglutaratecoated pitcofactorepigenomeexperimental studyfunctional lossglucose metabolismglucose transportglucose uptakehistone demethylaseinhibitorloss of functionmacrophagemetabolomemutantoverexpressionpreventreceptorrecruitresponserestorationretinal rodsscaffoldsubretinal injectionuptake
中文摘要
项目摘要/摘要
视网膜色素性视网膜炎(RP)视杆细胞感受器特异基因突变导致视网膜色素变性
周边和夜间视觉。但是,它是锥体函数的二次损失,导致
用于阅读、面部识别和其他日常工作的高分辨率日光视觉减弱
最让人疲惫的任务。导致RP锥体功能丧失的事件仍在继续
解体了。像其他神经元一样,光感受器依赖于葡萄糖,它们利用葡萄糖来
能量以及正在进行的合成以取代富含视觉色素的膜状外层
片段(OS)在每天接受光诱导的吞噬作用时。RPE充当
血-视网膜外屏障从脉络膜循环输送葡萄糖和营养物质
传给相邻的光感受器。我们提供的证据表明葡萄糖从RPE转运到
新的OS合成的光感受器与OS的吞噬作用有关。作为丰富的突变体
视杆细胞丢失,吞噬功能减弱,葡萄糖转运变短。
环路导致圆锥体饥饿。我们将研究信号通路的调节
RPE的葡萄糖转运和相关代谢体/表观基因组的变化
小鼠和猪的RP进展过程中的细胞,一个大型的RP动物模型,其中
圆锥体被集中成一条视觉条纹。
英文摘要
Project Summary/Abstract
Mutations in rod photoreceptor-specific genes in retinitis pigmentosa (RP) cause diminished
peripherial and night-time vision. But, it is secondary loss of cone function, leading to
diminished high-resolution daylight vision utilized for reading, facial recognition and other daily
tasks that is most debilitating. Events leading to loss of cone function in RP are still being
unraveled. Like other neurons, photoreceptors depend upon glucose, which they use for
energy as well as ongoing synthesis to replace visual pigment-rich membraneous outer
segments (OS) as they undergo daily light-induced phagocytosis. The RPE serves as a
blood-outer retinal barrier transporting glucose and nutrients from the choroid circulation
to adjacent photoreceptors. We provide evidence that glucose transport from the RPE to
photoreceptors for new OS synthesis is linked to OS phagocytosis. As abundant mutant
rod OS are lost and phagocytosis diminishes in RP, glucose transport becomes short-
circuited leading to cone starvation. We will examine the signaling pathway regulating
glucose transport from the RPE and linked metabolome/epigenome changes in these
cells during RP progression in both mice and pigs, a large animal model of RP where
cones are concentrated into a visual streak.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Blood outer retina barrier regulation
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项目类别:
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财政年份:2020
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负责人:DOUGLAS Chase DEAN
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依托单位:
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项目类别:
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Molecular Regulation of Epithelial-Mesenchymal Transitions
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Zeb1 and epithelial-mesenchymal balance in the eye
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Zeb1 and epithelial-mesenchymal balance in the eye
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财政年份:2002
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依托单位:
REGULATION OF VCAM-1 EXPRESSION BY INTERLEUKIN 4
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批准号:6356256
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项目类别:
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财政年份:2000
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依托单位:
REGULATION OF VCAM-1 EXPRESSION BY INTERLEUKIN 4
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批准号:6202525
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项目类别:
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资助金额:$21.12万
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财政年份:1999
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负责人:DOUGLAS Chase DEAN
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依托单位:
REGULATION OF VCAM-1 EXPRESSION BY INTERLEUKIN 4
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项目类别:
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资助金额:$21.12万
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财政年份:1998
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负责人:DOUGLAS Chase DEAN
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依托单位:
VCAM 1 EXPRESSION IN ENDOTHELIAL CELLS
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批准号:2735351
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项目类别:
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财政年份:1997
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负责人:DOUGLAS Chase DEAN
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依托单位:
REGULATION OF VCAM-1 EXPRESSION BY INTERLEUKIN 4
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批准号:6242714
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项目类别:
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资助金额:$20.36万
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财政年份:1997
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负责人:DOUGLAS Chase DEAN
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依托单位:
VCAM 1 EXPRESSION IN ENDOTHELIAL CELLS
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项目类别:
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财政年份:1997
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依托单位:
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项目类别:
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财政年份:1995
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负责人:DOUGLAS Chase DEAN
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依托单位:
RETINOBLASTOMA PROTEIN IN LUNG AND OTHER TISSUES
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财政年份:1995
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负责人:DOUGLAS Chase DEAN
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RETINOBLASTOMA PROTEIN IN LUNG AND OTHER TISSUES
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财政年份:1995
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负责人:DOUGLAS Chase DEAN
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依托单位:
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