Physiology of intrinsically photosensitive retinal ganglion cells
本质光敏视网膜神经节细胞的生理学
基本信息
- 批准号:9095318
- 负责人:
- 金额:$ 45.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-08-01 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAmacrine CellsApplications GrantsBehavioral AssayBiological ClocksBrainCellsDataDefectDependenceDevelopmentDiagnostic testsEye diseasesGanglion Cell LayerGenerationsGoalsGrantHeadacheHealthHormonesImageImmunohistochemistryIn VitroJet Lag SyndromeKnowledgeLabelLaboratoriesLasersLeadLearningLeber&aposs amaurosisLightLightingMalignant neoplasm of prostateMediatingMedicalMental DepressionMicroscopeMicroscopyMolecularNatural regenerationNatureNeuronsOphthalmological Diagnostic TechniquesOutputPatientsPersonsPhotoreceptorsPhotosensitivityPhototherapyPhysiologicalPhysiologyPlayPositioning AttributePreparationProcessProductivityPropertyPublic HealthPublishingPupilPupil light reflexReflex actionResearchRetinaRetinalRetinal ConeRetinal Ganglion CellsRetinitis PigmentosaRoleSchoolsShapesSignal TransductionSleep DisordersSleep Wake CycleSourceStructure of retinal pigment epitheliumSubconsciousSymptomsSynapsesTechnologyTestingTherapeuticVertebrate PhotoreceptorsVisionVisualVisual impairmentVisual system structureWhole-Cell RecordingsWorkalertnessbaseblindcancer riskcell typeconstrictiondepressive symptomsdesignganglion cellimprovedinnovationmalignant breast neoplasmmelanopsinmulti-electrode arraysneural circuitnew technologynovelresponsetooltwo-photon
项目摘要
DESCRIPTION (provided by applicant): The retina mediates various subconscious, photoadaptive responses to light, including pupil constriction, acute enhancement of alertness, regulating hormone secretion from the brain, and synchronizing the body clock to the light/dark cycle. Inadequate or mistimed induction of these responses, such as occurs in shift workers or the blind, can lead to "jet lag" symptoms, winter depression, sleep disorders, headache, and even breast and prostate cancer. Retinal input to the subconscious visual system is mediated by the intrinsically photosensitive retinal ganglion cells (ipRGCs), which generate intrinsic, melanopsin-based light responses as well as extrinsic, rod/cone-driven photoresponses. These neurons were discovered recently and much remains to be learned about how they respond to different kinds of light, and how they interact with other cells in the retina. This application's long-term objective is to fill both of these knowledge gaps and use this knowledge to help develop lighting technologies that promote health and productivity, light therapies for winter depression, better diagnostic tests for eye disorders, and medical innovations that ameliorate conditions of the visually impaired. This grant proposal consists of three Specific Aims. In aim 1,
whole-cell recordings will be made from ipRGCs identified using two-photon microscopy, and various pharmacological tools will be used to dissect the molecular and cellular mechanisms underlying these ganglion cells' rod/cone-driven responses to light. In aim 2, whole-cell recording, immunohistochemistry and confocal imaging will be used to identify retinal amacrine cells that receive input from ipRGCs, characterize their light-evoked responses, and determine their potential physiological functions. Aim 3 will use multielectrode-array recording, pharmacological manipulation and behavioral assays to determine the role of the retinal pigment epithelium (RPE) in the generation of ipRGCs' melanopsin-based light responses. The RPE is known to be crucial for the photosensitivity of the classical photoreceptors but their importance for ganglion-cell photoreceptors has not been fully investigated.
描述(由申请人提供):视网膜介导对光的各种潜意识、光适应性反应,包括瞳孔收缩、警觉性的急剧增强、调节大脑的激素分泌以及使生物钟与光/暗周期同步。这些反应的诱导不充分或不及时,例如轮班工人或盲人,可能会导致“时差”症状、冬季抑郁、睡眠障碍、头痛,甚至乳腺癌和前列腺癌。视网膜对潜意识视觉系统的输入是由内在光敏视网膜神经节细胞(ipRGC)介导的,它产生内在的、基于黑视蛋白的光反应以及外在的、视杆/视锥细胞驱动的光反应。这些神经元是最近发现的,关于它们如何对不同类型的光做出反应,以及它们如何与视网膜中的其他细胞相互作用,还有很多东西有待了解。该应用程序的长期目标是填补这两个知识空白,并利用这些知识帮助开发促进健康和生产力的照明技术、针对冬季抑郁症的光疗法、更好的眼部疾病诊断测试以及改善视障人士状况的医疗创新。该拨款提案包括三个具体目标。在目标 1 中,
全细胞记录将由使用双光子显微镜鉴定的 ipRGC 进行,并且将使用各种药理学工具来剖析这些神经节细胞视杆/视锥细胞驱动的光反应背后的分子和细胞机制。在目标 2 中,全细胞记录、免疫组织化学和共聚焦成像将用于识别从 ipRGC 接收输入的视网膜无长突细胞,表征其光诱发反应,并确定其潜在的生理功能。目标 3 将使用多电极阵列记录、药理学操作和行为测定来确定视网膜色素上皮 (RPE) 在 ipRGC 产生基于黑视蛋白的光响应中的作用。众所周知,RPE 对于经典感光细胞的光敏性至关重要,但其对于神经节细胞感光细胞的重要性尚未得到充分研究。
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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KWOON Y. WONG的其他文献
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{{ truncateString('KWOON Y. WONG', 18)}}的其他基金
Physiology of intrinsically photosensitive retinal ganglion cells
本质光敏视网膜神经节细胞的生理学
- 批准号:
8698759 - 财政年份:2013
- 资助金额:
$ 45.23万 - 项目类别:
Retrograde Signaling by Intrinsically Photosensitive Retinal Ganglion Cells
本质光敏视网膜神经节细胞的逆行信号传导
- 批准号:
9885119 - 财政年份:2013
- 资助金额:
$ 45.23万 - 项目类别:
Physiology of intrinsically photosensitive retinal ganglion cells
本质光敏视网膜神经节细胞的生理学
- 批准号:
8560727 - 财政年份:2013
- 资助金额:
$ 45.23万 - 项目类别:
Cross-talk between ganglion-cell photoreceptors and other neurons in the retina
神经节细胞感光器和视网膜其他神经元之间的串扰
- 批准号:
8240495 - 财政年份:2008
- 资助金额:
$ 45.23万 - 项目类别:
Cross-talk between ganglion-cell photoreceptors and other neurons in the retina
神经节细胞感光器和视网膜其他神经元之间的串扰
- 批准号:
8053770 - 财政年份:2008
- 资助金额:
$ 45.23万 - 项目类别:
Cross-talk between ganglion-cell photoreceptors and other neurons in the retina
神经节细胞感光器和视网膜其他神经元之间的串扰
- 批准号:
7448174 - 财政年份:2008
- 资助金额:
$ 45.23万 - 项目类别:
Cross-talk between ganglion-cell photoreceptors and other neurons in the retina
神经节细胞感光器和视网膜其他神经元之间的串扰
- 批准号:
7625897 - 财政年份:2008
- 资助金额:
$ 45.23万 - 项目类别:
Cross-talk between ganglion-cell photoreceptors and other neurons in the retina
神经节细胞感光器和视网膜其他神经元之间的串扰
- 批准号:
7978576 - 财政年份:2008
- 资助金额:
$ 45.23万 - 项目类别:
Retinal Inputs to the Mammalian Circadian Pacemaker
哺乳动物昼夜节律起搏器的视网膜输入
- 批准号:
7049350 - 财政年份:2005
- 资助金额:
$ 45.23万 - 项目类别:
Retinal Inputs to the Mammalian Circadian Pacemaker
哺乳动物昼夜节律起搏器的视网膜输入
- 批准号:
6938703 - 财政年份:2005
- 资助金额:
$ 45.23万 - 项目类别:
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