The Big Eye-dea: 3D/4D single cell resolution imaging of the mouse eye using lightsheet microscopy
Big Eye-dea:使用光片显微镜对小鼠眼睛进行 3D/4D 单细胞分辨率成像
基本信息
- 批准号:9533158
- 负责人:
- 金额:$ 23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-01 至 2019-07-31
- 项目状态:已结题
- 来源:
- 关键词:4D ImagingAdoptionAffectAutomobile DrivingBasic ScienceBig DataBlood VesselsCase StudyCellsCellular StructuresCommunitiesComputer softwareDataData SetDevelopmentDimensionsDisease ProgressionDisease modelDissectionEnvironmentEvaluationEyeEye diseasesGenerationsGlaucomaGoalsGrowthImageImage AnalysisImaging DeviceImaging TechniquesInjectableInvestigationKnowledgeLeadLightLocationMechanicsMethodsMicroscopeMicroscopyModelingMorphogenesisMorphologyMusNerve RegenerationOxygenPhysiologic Intraocular PressurePhysiologic pulseProcessPropertyProtocols documentationResearchResearch PersonnelResolutionRetinaRetinalRetinal DiseasesSlideSoftware ToolsStructureTechniquesTestingTherapeuticTimeTissuesTractionValidationVisionaxon growthcell behaviorcell motilitycell typecellular imagingdesignimaging approachimaging modalityimaging systemimprovedinnovationlive cell imagingmouse modelnerve stem cellneurovascularnovelnovel therapeuticsquantitative imagingrepairedsoftware developmentstem cell therapysuccesstherapeutic developmenttherapeutic evaluationthree dimensional structuretissue processingtooluser-friendly
项目摘要
Project Summary
The long-term goal of this study is to optimize a new rapid, quantitative imaging approach utilizing lightsheet
microscopy in order to dramatically improve the 3D and 4D cellular information obtainable from mouse models
of eye disease. During retinal disease, significant changes in cell and tissue morphology are common. In
retinopathies for example, excessive, thickened, bulbous, leaky blood vessels and abnormal `tufts' form,
protruding out of their usual layered locations. These malformed vessels cause many problems including the
generation of abnormal mechanical traction, which pulls on the different layers of the eye, eventually causing
the retina to detach. Understanding how and why cells grow into abnormal three-dimensional structures is key
to understanding retinal disease progression and treatment. However, current imaging techniques used to
investigate retinas at the cellular level are limited in terms of 3D information, due to a practical issue that the
naturally spherical eye tissue must be flattened to be viewed on a slide under the microscope. We therefore
propose to optimize the first lightsheet microscope protocol for mouse eye imaging as its design permits
imaging of large intact tissues, in their natural form, avoiding distortion through flattening of the 3D tissue.
Furthermore, the faster dissection method and rapid image acquisition (less than a minute to image an entire
eye) of the lightsheet microscope enables us to pursue the first robust method for live imaging of cell behavior
in the eye. Previous attempts at live imaging have seen limited success due again to the excessive flattening
and distortion of the spherical eye tissue required to transfer it onto a dish for conventional microscopy.
In storing high-resolution cellular information across large sections of eye tissue, and potentially also over
many time points in dynamic imaging, lightsheet microscopes generate very large datasets. The Big Data
issues incurred can cause significant scaling issues for standard image analysis software. We therefore
propose to develop easy to use, freely available computational software tools alongside optimization of the
imaging protocol in order to facilitate rapid adoption of the technique and maximize the quantitative information
obtainable by the wider community of eye disease researchers. Altogether we call this idea of an integrated
3D-4D imaging and analysis method the “Eye-dea approach”, standing for Eye – preserved Dimensional tissue
Environment Analysis. In this study we propose to demonstrate the advantages of the Eye-dea approach by
providing the first characterization of 3D and 4D cellular abnormalities in a retinopathy mouse model.
Furthermore we will demonstrate that the approach can overcome a current barrier to therapeutic progress: a
lack of 3D cellular imaging tools. Our test case is a potentially restorative glaucoma stem cell therapy. We will
quantify the level of functional integration of neuronal progenitor cells into the retinal layers of the eye, not
feasible with current imaging methods.
项目摘要
这项研究的长期目标是优化一种新的快速,定量成像方法利用光片
显微镜,以显着改善可从小鼠模型获得的3D和4D细胞信息
眼睛疾病。在视网膜疾病期间,细胞和组织形态的显著变化是常见的。在
视网膜病变,例如,过度的、增厚的、球状的、渗漏的血管和异常的“簇状”形式,
从它们通常的分层位置突出。这些畸形的血管引起许多问题,包括
产生异常的机械牵引力,牵引眼睛的不同层,最终导致
视网膜脱落了解细胞如何以及为什么会生长成异常的三维结构是关键
了解视网膜疾病的进展和治疗。然而,目前的成像技术用于
在细胞水平上研究视网膜在3D信息方面受到限制,这是由于
天然球形的眼组织必须被压平以在显微镜下的载玻片上观察。因此我们
建议优化第一个光片显微镜协议的小鼠眼睛成像,因为它的设计允许
以其自然形式对大的完整组织进行成像,避免通过使3D组织变平而产生失真。
此外,更快的解剖方法和快速的图像采集(不到一分钟即可对整个组织成像),
眼)的光片显微镜使我们能够追求第一个强大的方法,活的细胞行为成像
in the eye.由于过度的扁平化,先前的实时成像尝试已经看到了有限的成功
以及将其转移到用于常规显微镜的皿上所需的球形眼组织的变形。
在存储高分辨率的细胞信息跨越大部分眼组织,并可能也超过
在动态成像的许多时间点,光片显微镜产生非常大的数据集。大数据
所引起的问题可能导致标准图像分析软件的显著缩放问题。因此我们
建议开发易于使用,免费提供的计算软件工具,同时优化
成像协议,以促进该技术的快速采用,并最大限度地提高定量信息
更广泛的眼科疾病研究人员社区可以获得。总的来说,我们把这种综合的思想称为
3D-4D成像和分析方法“Eye-dea方法”,代表保存眼睛的三维组织
环境分析。在这项研究中,我们建议通过以下方式来证明Eye-dea方法的优势:
提供视网膜病变小鼠模型中3D和4D细胞异常的第一表征。
此外,我们将证明这种方法可以克服目前治疗进展的障碍:
缺乏3D细胞成像工具。我们的测试案例是一种潜在的恢复性青光眼干细胞疗法。我们将
量化神经元祖细胞功能整合到眼睛视网膜层的水平,而不是
用目前的成像方法。
项目成果
期刊论文数量(1)
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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Katie Bentley的其他文献
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{{ truncateString('Katie Bentley', 18)}}的其他基金
The Big Eye-dea: 3D/4D single cell resolution imaging of the mouse eye using lightsheet microscopy
Big Eye-dea:使用光片显微镜对小鼠眼睛进行 3D/4D 单细胞分辨率成像
- 批准号:
9166136 - 财政年份:2016
- 资助金额:
$ 23万 - 项目类别:
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