Structural and molecular determinants of duplex functionality in a pure-rod retina
纯杆状视网膜双工功能的结构和分子决定因素
基本信息
- 批准号:10334306
- 负责人:
- 金额:$ 14.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-21 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressBackCellsCharacteristicsColorConeDataDiseaseElasmobranchiiElementsExhibitsEyeFaceGene ExpressionGenesGeneticGenomeGoalsHybridsImageIn Situ HybridizationIndividualKineticsKnowledgeLeadLightLight AdaptationsLightingMammalian CellMediatingModelingMolecularMolecular StructureMorphologyNeuronsOpsinPathway interactionsPhotonsPhotoreceptorsPhysiologicalPopulationPresynaptic TerminalsProcessPropertyPublic HealthResearchRetinaRetinal ConeRetinal DegenerationRetinal PhotoreceptorsRodScanning Electron MicroscopySensorySignal TransductionSkatesSpatial DistributionSpeedStructureSynapsesSystemTestingTherapeuticVertebrate PhotoreceptorsVisionVisual system structureWorkbasecell typeexperiencefunctional adaptationfunctional plasticityinnovationinterestmRNA Expressionnovel strategiesparallel processingpatch clamppostsynapticresponseretinal neuronretinal rodssight restorationtranscriptometranscriptome sequencingvisual informationvisual processing
项目摘要
PROJECT SUMMARY/ABSTRACT:
Proper function in the duplex retina depends on the utilization of rods and cones in the processing of
visual information across the scotopic and photopic ranges of illumination. Importantly, when either type of
photoreceptor is lost during retinal degeneration, the remaining photoreceptors, be they rods or cones, cannot
perform the function of the opposite cell type. Most vertebrate retinae have this “duality” barrier and many
current vision restoration efforts are targeted towards replacing the lost photoreceptor population. However, the
elasmobranch L. erinacea (Little skate) has a pure-rod simplex retina, which can function under scotopic and
photopic illumination. We have a poor understanding of what factors govern this remarkable plasticity in the
skate retina, but a detailed knowledge of how this is achieved could hold the key to expanding the functional
repertoire of surviving rods or cones in diseased duplex retinae. We propose that the skate retina exhibits a
number of hybrid features on the molecular and ultrastructural levels that mediate its functional plasticity.
Furthermore, our preliminary data leads us to two main hypotheses: 1) Skate rods function under scotopic and
photopic conditions through a combination of morphological adaptations at the level of the synaptic terminal,
and genetic adaptations at the level of opsin expression; and: 2) The skate retina exhibits multiple adaptions in
the cell circuitry downstream of rods in order to accommodate for their functional plasticity. We have based
these predictions on several pieces of preliminary data. First, a long-wavelength sensitive opsin (LWS) can be
detected in the global genome of the skate. Second, multiple hybrid features are present at the ultrastructural
level in the synaptic terminals of the skate rods. Third, there is a 3-fold increase in the number of postsynaptic
processes that invaginate into a skate rod terminal, compared to rods from duplex retinae. Therefore, we will
test our hypotheses in the following specific aims: Aim 1: To analyze differences in gene expression in light-
and dark-adapted pure-rod retinae and uncover molecular mechanisms of functional plasticity. The objective of
Aim 1 is to determine what molecular factors mediate this unusual functional plasticity. Aim 2: To determine
the contribution of cell- and circuit-level structural and physiological characteristics mediating functional
plasticity in a pure-rod retina. The objectives of Aim 2 are to determine if skate rods posses ultrastructural
elements that mediate their functional plasticity, and if the retinal circuitry downstream of rods has evolved
specific structural and physiological attributes in order to accommodate for a wider range of inputs. The
proposed research is innovative because the simplex skate retina has evolved naturally to the present state
and allows us the unique opportunity to study and describe the properties of rod circuitry within the context of
an evolutionarily optimized visual system, unlike genetically modified rod-only models. It is significant because
it will reveal fundamental principles of functional adaptation in a naturally occurring monotypic retina, which
may lead to novel approaches in vision restoration efforts, especially after selective loss of photoreceptors.
PROJECT SUMMARY/ABSTRACT:
Proper function in the duplex retina depends on the utilization of rods and cones in the processing of
visual information across the scotopic and photopic ranges of illumination. Importantly, when either type of
photoreceptor is lost during retinal degeneration, the remaining photoreceptors, be they rods or cones, cannot
perform the function of the opposite cell type. Most vertebrate retinae have this “duality” barrier and many
current vision restoration efforts are targeted towards replacing the lost photoreceptor population. However, the
elasmobranch L. erinacea (Little skate) has a pure-rod simplex retina, which can function under scotopic and
photopic illumination. We have a poor understanding of what factors govern this remarkable plasticity in the
skate retina, but a detailed knowledge of how this is achieved could hold the key to expanding the functional
repertoire of surviving rods or cones in diseased duplex retinae. We propose that the skate retina exhibits a
number of hybrid features on the molecular and ultrastructural levels that mediate its functional plasticity.
Furthermore, our preliminary data leads us to two main hypotheses: 1) Skate rods function under scotopic and
photopic conditions through a combination of morphological adaptations at the level of the synaptic terminal,
and genetic adaptations at the level of opsin expression; and: 2) The skate retina exhibits multiple adaptions in
the cell circuitry downstream of rods in order to accommodate for their functional plasticity. We have based
these predictions on several pieces of preliminary data. First, a long-wavelength sensitive opsin (LWS) can be
detected in the global genome of the skate. Second, multiple hybrid features are present at the ultrastructural
level in the synaptic terminals of the skate rods. Third, there is a 3-fold increase in the number of postsynaptic
processes that invaginate into a skate rod terminal, compared to rods from duplex retinae. Therefore, we will
test our hypotheses in the following specific aims: Aim 1: To analyze differences in gene expression in light-
and dark-adapted pure-rod retinae and uncover molecular mechanisms of functional plasticity. The objective of
Aim 1 is to determine what molecular factors mediate this unusual functional plasticity. Aim 2: To determine
the contribution of cell- and circuit-level structural and physiological characteristics mediating functional
plasticity in a pure-rod retina. The objectives of Aim 2 are to determine if skate rods posses ultrastructural
elements that mediate their functional plasticity, and if the retinal circuitry downstream of rods has evolved
specific structural and physiological attributes in order to accommodate for a wider range of inputs. The
proposed research is innovative because the simplex skate retina has evolved naturally to the present state
and allows us the unique opportunity to study and describe the properties of rod circuitry within the context of
an evolutionarily optimized visual system, unlike genetically modified rod-only models. It is significant because
it will reveal fundamental principles of functional adaptation in a naturally occurring monotypic retina, which
may lead to novel approaches in vision restoration efforts, especially after selective loss of photoreceptors.
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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Ivan Anastassov其他文献
Ivan Anastassov的其他文献
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{{ truncateString('Ivan Anastassov', 18)}}的其他基金
Structural and molecular determinants of duplex functionality in a pure-rod retina
纯杆状视网膜双工功能的结构和分子决定因素
- 批准号:
10643883 - 财政年份:2021
- 资助金额:
$ 14.68万 - 项目类别:
Structural and molecular determinants of duplex functionality in a pure-rod retina
纯杆状视网膜双工功能的结构和分子决定因素
- 批准号:
10491873 - 财政年份:2021
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Characterization of TRPM1 isoforms and binding partners in ON bipolar cells
ON 双极细胞中 TRPM1 亚型和结合伴侣的表征
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9143132 - 财政年份:2014
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