Melanopsin-dependent light-evoked development of rod photoreceptors
Melanopsin-dependent light-evoked development of rod photoreceptors
批准号:
10735293
负责人:
Richard A. Lang
金额:
$40.13万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-30 至 2027-08-31
关键词:
AdultAmazeApoptosisBirthBlood VesselsCell DeathCessation of lifeConeDataDendritesDevelopmentDevelopmental ProcessEnvironmentEtiologyEyeEye DevelopmentEye diseasesG alpha q ProteinGTP-Binding ProteinsGlutamate ReceptorGlutamatesHealthHumanLabelLightLinkMediatingMusNeonatalNeuromodulatorPathway interactionsPatternPerinatalPhotoreceptorsProcessPublic HealthRecording of previous eventsRetinaRetinal Ganglion CellsRetinal PhotoreceptorsRodSensoryStructureStudy modelsSystems DevelopmentTestingTimeTractionVisualVisual SystemWorkdark rearingdesignexperiencegenetic approachglutamatergic signalinginterestintimate behaviorloss of functionmelanopsinnovelorgan growthpostnatalprecursor cellpreventprogenitorresponseretinal neuronretinal rodssensorsingle cell analysissingle cell sequencingvision development
中文摘要
已经知道视觉系统的发展可以是自适应的
光曝光或视觉体验改变最终结构的过程。在这里我们
建议研究通过OPN4的光接收的发育途径
固有的光敏性视网膜神经节细胞(IpRGCs)对视杆感受器的调节
生死存亡。初步数据显示,光和OPN4调节视杆前体细胞的死亡。
成年小鼠的新生视网膜和视杆细胞数。这是由神经调节剂谷氨酸调节的。
我们认为,ipRGC视网膜外树突(ORD)将谷氨酸输送到视网膜外,并
规范棒的存活期。ORD是ipRGC独有的,是暂时的,仅在第一个期间存在
出生后一周。单细胞测序数据显示谷氨酸受体Grik3表达
在出生后第一周短暂地出现在杆状前体中,因此是一个很好的介导者
这样的回应。这些数据表明,围产期光感知的中心假设是
IpRGCs通过谷氨酸诱导的前体细胞死亡来调节杆状感光细胞的数量。
我们提出了三个目标,旨在定义这种拟议的自适应机制
回应。我们将确定ODS的发展时间进程,并评估ODS的标志物
谷氨酸功能(目标1),评估LIGHT-OPN4-GαQ-杆细胞中所提出的关系
死亡途径(目标2),并评估ipRGC Ords的谷氨酸递送和ROD的反应
前体(目标3)。早期发育的光感知调节数量的发现
是出乎意料的,并引起了广泛的兴趣,因为它代表了一种新的
机制,并对人眼发育有影响。
英文摘要
It has been known for some time that development of the visual system can be an adaptive
process in which light exposure or visual experience modifies the final structure. Here we
propose to investigate a developmental pathway in which photoreception via OPN4 in
intrinsically photosensitive retinal ganglion cells (ipRGCs) regulates rod photoreceptor
survival. Preliminary data show that light and OPN4 regulate rod precursor cell death in the
neonatal retina and rod number in adult mice. This is mediated by the neuromodulator glutamate.
We suggest that ipRGC outer retinal dendrites (ORDs) deliver glutamate to the outer retina and
regulate rod survival. ORDs are unique to ipRGCs and are transient, existing only during the first
week after birth. Single cell sequencing data reveal that the glutamate receptor Grik3 is expressed
in rod precursors transiently in the first week after birth and is thus a good candidate to mediate
this response. These data suggest the Central Hypothesis that Perinatal light sensing by
ipRGCs regulates rod photoreceptor number via glutamate-induced precursor cell death.
We propose three Aims designed to define the mechanisms underlying this proposed adaptive
response. We will define the developmental time-course of ORDs and assess markers of
glutamate function (Aim 1), assess the proposed relationships in the light-OPN4-Gαq-rod cell
death pathway (Aim 2), and assess glutamate delivery by ipRGC ORDs and the response of rod
precursors (Aim 3). The finding that early developmental light sensing regulates the number
of rod photoreceptors is unexpected and of broad interest because it represents a novel
mechanism and has implications for human eye development.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Mechanisms of intrinsic light responses in the ocular lens
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批准号:10426249
-
项目类别:
-
资助金额:$37.12万
-
财政年份:2021
-
负责人:Richard A. Lang
-
依托单位:
Light regulated vascular development in the eye via the Hippo pathway
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批准号:10322455
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项目类别:
-
资助金额:$41.94万
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财政年份:2021
-
负责人:Richard A. Lang
-
依托单位:
Mechanisms of intrinsic light responses in the ocular lens
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批准号:10636950
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项目类别:
-
资助金额:$38.18万
-
财政年份:2021
-
负责人:Richard A. Lang
-
依托单位:
Light regulated vascular development in the eye via the Hippo pathway
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批准号:10544744
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项目类别:
-
资助金额:$43.23万
-
财政年份:2021
-
负责人:Richard A. Lang
-
依托单位:
Regulation of vascular development in the eye by an opsin 5-dependent clock
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批准号:9769754
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项目类别:
-
资助金额:$47.86万
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财政年份:2016
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负责人:Richard A. Lang
-
依托单位:
Regulation of vascular development in the eye by an opsin 5-dependent clock
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批准号:9336304
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项目类别:
-
资助金额:$47.86万
-
财政年份:2016
-
负责人:Richard A. Lang
-
依托单位:
Regulation of vascular development in the eye by an opsin 5-dependent clock
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批准号:9551622
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项目类别:
-
资助金额:$47.86万
-
财政年份:2016
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负责人:Richard A. Lang
-
依托单位:
Retinal Microglia and Angiogenesis
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批准号:8310517
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项目类别:
-
资助金额:$38.25万
-
财政年份:2012
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负责人:Richard A. Lang
-
依托单位:
Retinal Microglia and Angiogenesis
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批准号:8461948
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项目类别:
-
资助金额:$36.34万
-
财政年份:2012
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负责人:Richard A. Lang
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依托单位:
Retinal Microglia and Angiogenesis
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批准号:8658090
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项目类别:
-
资助金额:$37.49万
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财政年份:2012
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负责人:Richard A. Lang
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依托单位:
RhoGTPases in Early Eye Development
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批准号:7178055
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项目类别:
-
资助金额:$30.0万
-
财政年份:2007
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负责人:Richard A. Lang
-
依托单位:
RhoGTPases in Early Eye Development
-
批准号:7394331
-
项目类别:
-
资助金额:$29.4万
-
财政年份:2007
-
负责人:Richard A. Lang
-
依托单位:
RhoGTPases in Early Eye Development
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批准号:8035896
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项目类别:
-
资助金额:$32.08万
-
财政年份:2007
-
负责人:Richard A. Lang
-
依托单位:
RhoGTPases in Early Eye Development
-
批准号:7583884
-
项目类别:
-
资助金额:$33.75万
-
财政年份:2007
-
负责人:Richard A. Lang
-
依托单位:
RhoGTPases in Early Eye Development
-
批准号:7796663
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项目类别:
-
资助金额:$33.41万
-
财政年份:2007
-
负责人:Richard A. Lang
-
依托单位:
Developing vision: Cadherin function in lens morphogenesis
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批准号:7487745
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项目类别:
-
资助金额:$35.69万
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财政年份:2005
-
负责人:Richard A. Lang
-
依托单位:
Developing vision: Cadherin function in lens morphogenesis
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批准号:7121099
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项目类别:
-
资助金额:$36.62万
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财政年份:2005
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负责人:Richard A. Lang
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依托单位:
Wnt Pathway Regulation of Lens Polarity
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批准号:8625305
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项目类别:
-
资助金额:$37.49万
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财政年份:2005
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负责人:Richard A. Lang
-
依托单位:
Wnt Pathway Regulation of Lens Polarity
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批准号:8435500
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项目类别:
-
资助金额:$36.34万
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财政年份:2005
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负责人:Richard A. Lang
-
依托单位:
Wnt Pathway Regulation of Lens Polarity
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批准号:8227999
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项目类别:
-
资助金额:$38.25万
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财政年份:2005
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负责人:Richard A. Lang
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依托单位:
海外基金