Accelerating vision restoration with in-vivo cellular imaging of retinal function

通过视网膜功能的体内细胞成像加速视力恢复

基本信息

批准号：
9292320
负责人：
DAVID R WILLIAMS
金额：
$ 72.37万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9292320
关键词：
Animal Model Animals Antioxidants Automobile Driving Biological Preservation Biomedical Research Blindness Cell physiology Cells Cellular Structures Collaborations Cone Development Eye Feedback Functional Imaging Genetic Transcription Goals Halorhodopsins Human Image Imaging Device Imaging Techniques Imaging technology Implant Individual Institutes Institution Laboratories Light Light Cell Location Macaca Measures Metabolism Methods Modeling Monitor Monkeys Mus NADP Neurons Neurophysiology - biologic function Output Peroxides Photophobia Photoreceptors Phototoxicity Primates Production Reporter Research Personnel Resolution Retina Retinal Retinal Degeneration Retinal Ganglion Cells Retinitis Pigmentosa Rhodopsin Societies Stem cells Structure Technology Time Translating Transplantation Universities Up-Regulation Validation Viral Vector Virus Vision Visual Pathways Wisconsin adaptive optics adaptive optics scanning laser ophthalmoscopy blind calcium indicator cellular imaging collaborative environment design ganglion cell gene therapy imaging modality implantation improved in vivo in vivo two-photon imaging induced pluripotent stem cell medical schools mouse model new technology novel novel therapeutic intervention optical imaging optogenetics public health relevance relating to nervous system response restoration stem cell therapy subretinal injection success technology development therapy development tool two-photon vision development

项目摘要

DESCRIPTION (provided by applicant): The lack of methods to image functioning retinal circuitry in the living eye is a fundamental impediment to all efforts at vision restoration. The ability to assess the structure and function of retinal circuitry in vivo at multiple retinal layer simultaneously will not only transform our understanding of where different vision restoration strategies succeed and fail, the feedback these tools will provide will greatly shorten the development cycle for all approaches in which they are deployed. Investigators in the Advanced Retinal Imaging Alliance (ARIA) at the University of Rochester (Jennifer Hunter, Bill Merigan, and David Williams) will create a new retinal imaging tool designed to track changes in structure and function in both the inner and outer retina at cellular resolution in individual animals over time. This tool will combine two-photon, adaptive optics imaging of genetically-encoded calcium indicators to track the neuronal responses of individual photoreceptors and ganglion cells in two different animal models, mouse and monkey. We will assess the value of this imaging technology in three different approaches to vision restoration. Applying these tools to a gene therapy approach, the Rochester team will collaborate with Connie Cepko's laboratory at Harvard University to rescue cone function in retinitis pigmentosa through the up-regulation of anti-oxidants. We will demonstrate the value of these imaging tools for an optogenetics approach by expressing channel-rhodopsin in monkey cones in collaboration with Botond Roska at the Miescher Institute for Biomedical Research. This effort will also develop a primate model of retinal degeneration in which a viral vector is used to shave off photoreceptor outer segments. Finally, these imaging tools will be deployed to monitor the differentiation and neural connectivity of stem cells in mouse and then monkey in collaboration with David Gamm at the University of Wisconsin, Madison. This consortium will not only develop advanced imaging technology, it will translate it to the field of vision restoration, and create a collaborative environment for sharing best practices and combining different approaches.

描述（由适用提供）：缺乏在活眼中图像功能性视网膜电路的方法是对视力恢复的所有努力的根本障碍。在多个视网膜层中评估体内视网膜电路的结构和功能的能力不仅会改变我们对不同视力恢复策略成功和失败的理解，而且这些工具将提供的反馈将大大缩短其部署的所有方法的开发周期。罗切斯特大学高级视网膜成像联盟（ARIA）的研究人员（Jennifer Hunter，Bill Merigan和David Williams）将创建一个新的视网膜成像工具，旨在跟踪单个动物随时间的细胞分辨率在蜂窝分辨率的内部和外部视网膜中的结构和功能变化。该工具将结合遗传编码的钙指示剂的两光自适应光学成像，以跟踪两个不同动物模型（小鼠和猴子）中单个光感受器和神经节细胞的神经元反应。我们将以三种不同的视觉恢复方法评估这种成像技术的价值。罗切斯特团队将这些工具应用于基因治疗方法，将与哈佛大学的康妮·塞普科（Connie Cepko）的实验室合作，通过上调抗氧化剂来挽救色素性视网膜炎的锥体功能。我们将通过与Miescher生物医学研究所的Botond Roska合作表达猴子锥中的通道 - ropopsin通过在猴子锥中表达频道 - 偶像蛋白来证明这些成像工具的价值。这项工作还将开发出视网膜变性的私人模型，其中使用病毒载体分享光感受器的外部段。最后，将部署这些成像工具，以监视鼠标中干细胞的分化和神经元连接性，然后与麦迪逊大学威斯康星大学的David Gamm合作进行猴子的合作。该财团不仅将开发高级成像技术，还将将其转化为视觉恢复领域，并创建一个协作环境，以共享最佳实践和结合不同的方法。