Ganglion Cell Function in Retinal Disease
神经节细胞在视网膜疾病中的功能
基本信息
- 批准号:8045368
- 负责人:
- 金额:$ 38.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-02-01 至 2015-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAfferent NeuronsAgeAmacrine CellsCationsCell physiologyCellsDataDefectDetectionDevelopmentDevelopmental Delay DisordersDiagnosisDiseaseElectroretinographyEyeFunctional disorderFundingGenesGlutamate ReceptorGlutamatesGoalsHumanIndividualInvestigationLeadLightMasksMediatingModelingMotionMusMutant Strains MiceMutationNatureNervous system structureNight BlindnessPathway interactionsPatientsPatternPeripheralPhenotypePhotoreceptorsPhylogenetic AnalysisPlayPrimatesPrincipal InvestigatorProcessPropertyResearchRestRetinaRetinalRetinal DiseasesRetinal Ganglion CellsRoleSensorySignal TransductionStimulusSynapsesTestingTherapeuticVisionVisualVisuospatialWorkdisease phenotypeganglion cellinformation processingluminancemouse modelmutantneural circuitprogramspublic health relevancereceptive fieldreceptorresearch studyresponsescaffoldvision developmentvisual processvisual processing
项目摘要
DESCRIPTION (provided by applicant): The goals of this research are focused on understanding signaling mechanisms that regulate the development of visual function and spatial organization of retinal ganglion cells and how they are altered in retinal disease. Normal vision begins in the retina and is initiated by photoreceptor detection of light. Parallel pathways of information flow are initiated at the first synapse between photoreceptors and depolarizing and hyperpolarizing bipolar cells, which detect luminance increases and decreases and/or vision under dark- and light-adapted conditions. As a result, the pathways extend the dynamic range of information processing in the intensity domain, and increase specialization of information processing for salient environmental features, e.g., motion, direction and size. Signaling within these circuits is refined by inhibitory inputs in the outer and inner retina and these interactions culminate in and define the receptive field organization of the retinal ganglion cells. The receptive field is a basic property, shared across all sensory neurons in all species. It defines the types and range of environmental stimuli that each cell encodes. Thus, understanding how receptive field properties develop is key to understanding visual function in the retina and the ganglion cells are a vital part because they represent both the culmination of all retinal processing and the scaffold for the rest of visual processing. Because basic RF spatial organization is already present at the onset of visual responses in ganglion cells, the processes underlying their development have been relatively intractable to investigation. That normal vision requires signaling through the depolarizing and hyperpolarizing pathways is amply indicated by the visual defects that occur in patients with and mouse models of congenital stationary night blindness (CSNB), where depolarizing bipolar cell processing is eliminated. We have three unique mouse models of CSNB1 that we will continue to use to probe the synaptic circuitry underlying CSNB, in which normal photoreceptor function is retained. The nature of the changes in spontaneous and visually-evoked responses across GCs in the three mutants provides a unique opening to study the development of receptive field organization and ganglion cell signaling. The phylogenetic conservation of receptive field organization suggests that our findings in the mouse will be relevant to primate peripheral retinal processing. We suggest that the characterization of these mouse models represents a significant opportunity, not afforded by other mouse or vertebrate models and represents a critical step in our understanding both the disease mechanisms in CSNB1 and normal retinal development and function.
PUBLIC HEALTH RELEVANCE: This proposal seeks to understand the mechanisms that govern the development of vision in the retina and to investigate the changes in the downstream synaptic mechanisms when signaling is eliminated from one of the parallel pathways of information processing in the retina. One focus is to understand the exact changes that occur in complete congenital stationary night blindness, a retinal disease that does not involve photoreceptor dysfunction or morphological defects. A second focus is to understand the fundamental processes that regulate the development of normal retinal function, particularly in the ganglion cells. We believe that our results will guide diagnosis and therapeutic approaches to restore or rescue CSNB and also will be relevant to other blinding diseases in people of all ages.
描述(由申请人提供):本研究的目标是了解调节视网膜神经节细胞视觉功能和空间组织发育的信号传导机制,以及它们在视网膜疾病中如何改变。正常的视觉开始于视网膜,并由光感受器对光的检测启动。信息流的平行通路在光感受器与去极化和超极化双极细胞之间的第一突触处启动,所述双极细胞在黑暗和光适应条件下检测亮度增加和减少和/或视觉。结果,这些路径扩展了强度域中的信息处理的动态范围,并且增加了针对显著环境特征的信息处理的专业化,例如,运动方向和大小这些回路内的信号通过外视网膜和内视网膜中的抑制性输入而被细化,并且这些相互作用最终导致并定义视网膜神经节细胞的感受野组织。感受野是所有物种的所有感觉神经元所共有的基本属性。它定义了每个细胞编码的环境刺激的类型和范围。因此,理解感受野特性如何发展是理解视网膜视觉功能的关键,而神经节细胞是至关重要的部分,因为它们代表了所有视网膜处理的顶点和其余视觉处理的支架。由于基本的RF空间组织已经存在于神经节细胞的视觉反应的发病,其发展的过程一直是相对棘手的调查。正常的视觉需要通过去极化和超极化通路的信号传导,这在先天性静止性夜盲(CSNB)患者和小鼠模型中发生的视觉缺陷中得到了充分的指示,其中去极化双极细胞处理被消除。我们有三种独特的CSNB 1小鼠模型,我们将继续使用它们来探测CSNB背后的突触回路,其中保留了正常的感光功能。在三个突变体的GC自发和视觉诱发反应的变化的性质提供了一个独特的开放研究的发展感受野组织和神经节细胞信号。感受野组织的系统发育保守性表明,我们在小鼠中的发现将与灵长类动物外周视网膜处理有关。我们认为,这些小鼠模型的表征代表了一个重要的机会,而不是由其他小鼠或脊椎动物模型提供的,代表了我们理解CSNB 1和正常视网膜发育和功能的疾病机制的关键一步。
公共卫生关系:该提案旨在了解视网膜中控制视觉发展的机制,并研究当信号从视网膜中信息处理的平行通路之一消除时下游突触机制的变化。其中一个重点是了解完全先天性静止性夜盲症的确切变化,这是一种不涉及感光细胞功能障碍或形态缺陷的视网膜疾病。第二个重点是了解调节正常视网膜功能发展的基本过程,特别是在神经节细胞中。我们相信,我们的研究结果将指导诊断和治疗方法,以恢复或挽救CSNB,也将是相关的其他致盲性疾病的人的所有年龄。
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)
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Maureen A McCall其他文献
Maureen A McCall的其他文献
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{{ truncateString('Maureen A McCall', 18)}}的其他基金
FASEB SRC Retinal Neurobiology & Visual Processing
FASEB SRC 视网膜神经生物学
- 批准号:
8675254 - 财政年份:2012
- 资助金额:
$ 38.03万 - 项目类别:
FASEB SRC Retinal Neurobiology & Visual Processing
FASEB SRC 视网膜神经生物学
- 批准号:
9068312 - 财政年份:2012
- 资助金额:
$ 38.03万 - 项目类别:
FASEB SRC Retinal Neurobiology & Visual Processing
FASEB SRC 视网膜神经生物学
- 批准号:
8459391 - 财政年份:2012
- 资助金额:
$ 38.03万 - 项目类别:
FASEB SRC Retinal Neurobiology & Visual Processing
FASEB SRC 视网膜神经生物学
- 批准号:
8316891 - 财政年份:2012
- 资助金额:
$ 38.03万 - 项目类别:
FASEB Summer Research Conference on Retinal Neurobiology and Visual Processing
FASEB 视网膜神经生物学和视觉处理夏季研究会议
- 批准号:
8004284 - 财政年份:2010
- 资助金额:
$ 38.03万 - 项目类别:
GABAc Receptors & Mouse Retinal Ganglion Cell Responses
GABAc 受体
- 批准号:
7502391 - 财政年份:2004
- 资助金额:
$ 38.03万 - 项目类别:
GABAc Receptors & Mouse Retinal Ganglion Cell Responses
GABAc 受体
- 批准号:
7177463 - 财政年份:2004
- 资助金额:
$ 38.03万 - 项目类别:
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