Metabolism of Lactate in the Outer Retina
Metabolism of Lactate in the Outer Retina
批准号:
8633768
负责人:
NEAL S. PEACHEY
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-04-01 至 2017-03-31
关键词:
AgeAnatomyAstrocytesBiochemicalBrainCatabolismCell RespirationCellsCouplingDiseaseEnergy MetabolismEnergy-Generating ResourcesFibroblastsGene ExpressionGeneticGlucoseHealthHeterozygoteKnock-outMalignant NeoplasmsMetabolicMetabolic PathwayMetabolismMitochondriaModelingMolecularMusMutant Strains MiceNeurogliaNeuronsOxidative PhosphorylationPatternPhenotypePhotoreceptorsPhototransductionPlayPopulationProteinsResearchRetinaRetinalRetinal ConeRetinal DiseasesRetinal PhotoreceptorsRoleSourceTechniquesTestingTissuesVertebrate PhotoreceptorsVeteransVisionVisualaerobic glycolysiscell typeextracellularinsightmouse modelneoplastic cellneuronal survivalpublic health relevanceretinal neuronretinal rodsrhouptake
中文摘要
视网膜的能量需求是人体中最高的。葡萄糖是
代谢以满足这一需求,但不被认为是
视网膜神经元。相反,来自神经胶质细胞的乳酸被认为是一种重要的能量。
消息来源。这一假说得到了单羧酸转运蛋白独特模式的支持
(MCTs),其中MCT1由光感受器表达,MCT4表达
特异于M?ller胶质细胞,是支持光感受器功能的主要神经胶质细胞
多方面的。这一假说也被严重的小鼠视网膜表型所支持
缺乏CD147,这是一种正常表达MCT1所必需的辅助蛋白。我们会
使用MCT1、MCT4和CD147的系统性和条件性小鼠模型来定义角色
支持视网膜能量代谢的MCTs对乳酸及其运输的研究。这个项目是
由两个具体目标组成。目标1将描述一个新成立的视网膜
MCT4突变小鼠,利用视觉电生理、解剖和生化
接近了。AIM 2将把同样的技术应用于MCT1突变小鼠。首先,我们会
比较MCT1/-杂合子和野生型小鼠的视网膜表型。
由于MCT1基因敲除不能存活,我们将消除MCT1在杆状病毒和/或
视锥感光细胞CD147的细胞特异性缺失。在这个项目完成后,我们
将了解MCT1和MCT4在支持新陈代谢和生存中所起的作用
杆状和锥状感光器。我们将知道M?ler神经胶质细胞是否是一个重要的
视网膜乳酸的来源以及乳酸是否是视杆细胞和/或视杆细胞的重要能量来源
视锥感光细胞新陈代谢。这项研究将为外部世界提供重要的见解
视网膜新陈代谢,将为理解外周疾病提供一个框架
视网膜。
英文摘要
The energy demands of the retina are some of the highest in the body. Glucose is
metabolized to satisfy this demand, but is not thought to be the primary substrate used by
retinal neurons. Instead, lactate derived from glial cells is thought to be an important energy
source. This hypothesis is supported by the unique pattern of monocarboxylate transporters
(MCTs) in the retina, in which MCT1 is expressed by photoreceptors and MCT4 expression is
specific to M¿ller glial cells, the primary glial cell that supports photoreceptor function in
multiple ways. The hypothesis is also supported by the severe retinal phenotype of mice
lacking CD147, an accessory protein that is required for normal MCT1 expression. We will
use systemic and conditional mouse models for MCT1, MCT4, and CD147 to define the role
of lactate and its transport by MCTs in support of retinal energy metabolism. This project is
comprised of two Specific Aims. Aim 1 will characterize the retina of a newly established
Mct4 mutant mouse, using visual electrophysiological, anatomical and biochemical
approaches. Aim 2 will apply these same techniques to Mct1 mutant mice. First we will
compare the retinal phenotype of Mct1+/-heterozygotes with that of wild type littermates.
Since the Mct1 knock-out does not survive, we will eliminate Mct1 expression in rod and/or
cone photoreceptors by cell-specific deletion of CD147. At the completion of this project, we
will understand the role that MCT1 and MCT4 play in supporting metabolism and survival of
rod and cone photoreceptors. We will know whether M¿ller glial cells are an important
source of retinal lactate and whether lactate is an important source of energy for rod and/or
cone photoreceptor metabolism. This research will provide important insights into outer
retinal metabolism and will provide a framework for understanding diseases of the outer
retina.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
BLR&D Research Career Scientist Award
-
批准号:10451509
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2020
-
负责人:NEAL S. PEACHEY
-
依托单位:
BLR&D Research Career Scientist Award
-
批准号:10618297
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2020
-
负责人:NEAL S. PEACHEY
-
依托单位:
Deciphering Genetic and Environmental Influences on Visual Disorders in the Million Veteran Program
-
批准号:10454826
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2019
-
负责人:NEAL S. PEACHEY
-
依托单位:
Deciphering Genetic and Environmental Influences on Visual Disorders in the Million Veteran Program
-
批准号:9918755
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2019
-
负责人:NEAL S. PEACHEY
-
依托单位:
Deciphering Genetic and Environmental Influences on Visual Disorders in the Million Veteran Program
-
批准号:10158432
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2019
-
负责人:NEAL S. PEACHEY
-
依托单位:
Metabolism of Lactate in the Outer Retina
-
批准号:8815004
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2014
-
负责人:NEAL S. PEACHEY
-
依托单位:
Metabolism of Lactate in the Outer Retina
-
批准号:8974361
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2014
-
负责人:NEAL S. PEACHEY
-
依托单位:
The Mouse dc-Electroretinogram
-
批准号:6954115
-
项目类别:
-
资助金额:$22.95万
-
财政年份:2003
-
负责人:NEAL S. PEACHEY
-
依托单位:
The Mouse dc-Electroretinogram
-
批准号:6779919
-
项目类别:
-
资助金额:$22.95万
-
财政年份:2003
-
负责人:NEAL S. PEACHEY
-
依托单位:
The Mouse dc-Electroretinogram
-
批准号:6679348
-
项目类别:
-
资助金额:$22.35万
-
财政年份:2003
-
负责人:NEAL S. PEACHEY
-
依托单位:
OSCILLATORY POTENTIALS IN RETINAL DISEASE
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批准号:3038843
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项目类别:
-
资助金额:$0.08万
-
财政年份:1987
-
负责人:NEAL S. PEACHEY
-
依托单位:
OSCILLATORY POTENTIALS IN RETINAL DISEASE
-
批准号:3038844
-
项目类别:
-
资助金额:$2.5万
-
财政年份:1987
-
负责人:NEAL S. PEACHEY
-
依托单位:
OSCILLATORY POTENTIALS IN RETINAL DISEASE
-
批准号:3038841
-
项目类别:
-
资助金额:$1.92万
-
财政年份:1987
-
负责人:NEAL S. PEACHEY
-
依托单位:
海外基金