Interferometric Optophysiology of the Human Retina

人类视网膜的干涉光生理学

• 批准号: 10004318
• 负责人: Austin Roorda
• 金额: $ 9.17万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004318
• 关键词: Address; Cell membrane; Cells; Clinical; Collaborations; Electrodes; Elements; Eye; Eye Movements; Generations; Geometry; Goals; Human; Image; In Vitro; Individual; Interferometry; Ions; Length; Light; Measurement; Measures; Membrane; Microscopy; Monitor; Natural regeneration; Neurons; Ophthalmology; Optics; Pattern; Phase; Photoreceptors; Physiological; Physiology; Positioning Attribute; Primates; Psychophysics; Resolution; Retina; Retinal; Retinal Diseases; Retinal Ganglion Cells; Scanning; System; Technology; Testing; Universities; Visible Radiation; Vision; Work; adaptive optics; adaptive optics scanning laser ophthalmoscopy; base; electrical measurement; in vivo; in vivo imaging; innovation; nanoscale; neurotransmission; new technology; novel strategies; optical imaging; phase change; relating to nervous system; retinal imaging; retinal neuron; targeted delivery; tool; transmission process; visual processing

Project Summary/Abstract Our goal is to develop a new technology for non-invasive optical monitoring of activity of individual retinal neurons and their light-driven inputs, at cellular resolution, in the living human retina. If successful, this technology will provide an entirely new and objective approach to understand and monitor treatment of retinal disease, thereby transforming scientific studies of the eye and vision. This project directly addresses the priorities outlined in the RFA-EY-14-001, the first RFA within the NEI Audacious Goal Initiative. The proposed work relies on combining and validating two new approaches. First, interferometry (including phase-resolved OCT; Park Lab at UC Riverside) can, in principle, be used to measure nanometer- scale distortions in the membranes of cells that occur during membrane depolarization and ion influx. With depth resolution, these measurements will enable us to measure neural activity non-invasively, throughout the layers of the retina, at cellular resolution. Second, adaptive optics scanning laser ophthalmoscopy (Roorda Lab at UC Berkeley) and image-based eye tracking can be used to position stimulating and measurement beams on the retina with cellular precision in the living eye, by overcoming optical aberrations and eye jitter. This technology will allow us to activate individual photoreceptors and groups of photoreceptors with visible light while imaging the resulting electrical activity of individual downstream cells, in vivo. To advance and combine these approaches requires a stepwise aggregation of technology. In a unique collaboration, we will build on simpler wide-field interferometric measurements of electrical activity in isolated retina (Palanker Lab at Stanford University), combined with large-scale multi-electrode physiological measurements in primate retina (Chichilnisky Lab at Stanford University) to validate and tune the optical measurements. Ultimately, the innovation at each step forms a powerful tool, independently or with a combination of other approaches, and finds applicability to optical imaging, retinal physiology, psychophysics and clinical ophthalmology. The specific aims are: Aim 1. Wide-field interferometry for measuring patterns of electrical activity in primate retina Depolarization during neural signaling produces nanometer-scale deformations in cells that are detectable with interferometry. The simplest approach is wide-field interferometric microscopy with transmission geometry in isolated retina. We will measure depth-resolved optical phase changes produced by neural activity in primate retina, and use them for physiological characterizations of many retinal ganglion cells (RGCs) and other retinal neurons simultaneously. Aim 2. Phase-resolved OCT for reflectance measurements of patterns of retinal activity The next step toward human application is phase-resolved OCT; essentially, low-coherence interferometry and well-established tool for in vivo imaging. We will record optical path length changes associated with neural activity in reflection geometry using point-scanning, near-IR (1060 nm), phase-resolved OCT on isolated primate retina. Aim 3. Adaptive optics, eye tracking and phase-resolved OCT for measuring human retinal function Deployment in humans requires compensating for optical aberrations in the eye as well as eye movements. We will develop a system that uses AOSLO to image the retina for eye tracking, targeted delivery of stimulation light, and positioning of the OCT probe. We will test this system in humans and demonstrate its potential application in clinical settings.

项目总结/摘要 我们的目标是开发一种新的技术，用于非侵入性的光学监测个体视网膜的活动。 神经元和它们的光驱动输入，在细胞分辨率，在活的人类视网膜。如果成功，这 技术将提供一种全新和客观的方法来理解和监测视网膜病变的治疗， 疾病，从而改变了眼睛和视觉的科学研究。该项目直接针对 RFA-EY-14-001中概述的优先事项，这是NEI大胆目标倡议中的第一个RFA。 拟议的工作依赖于结合和验证两种新方法。第一，干涉测量法 （包括相位分辨OCT;加州大学滨江分校的Park Lab）原则上可以用于测量纳米级的光学厚度。 细胞膜去极化和离子流入期间发生的细胞膜尺度扭曲。与 深度分辨率，这些测量将使我们能够在整个过程中无创地测量神经活动。 细胞分辨率下的视网膜层。第二，自适应光学扫描激光检眼镜（Roorda Lab 和基于图像的眼睛跟踪可以用于定位刺激和测量光束 通过克服光学像差和眼睛抖动，以活体眼睛中的细胞精度在视网膜上进行。这 技术将使我们能够用可见光激活单个感光器和感光器组 同时在体内成像单个下游细胞的所得电活动。 为了推进和联合收割机这些方法需要逐步聚合技术。中 独特的合作，我们将建立在更简单的宽场干涉测量的电活动， 离体视网膜（斯坦福大学的Palanker实验室），结合大规模多电极生理 灵长类动物视网膜中的光学测量（斯坦福大学的Chichilnisky实验室）来验证和调整光学测量。 测量. 最终，每一步的创新都形成了一个强大的工具，无论是独立的还是与以下因素的结合 其他方法，并发现适用于光学成像，视网膜生理学，心理物理学和临床 眼科具体目标是： 目标1.宽视场干涉法测量灵长类动物视网膜电活动模式 神经信号传导过程中的去极化在细胞中产生纳米级的变形， 干涉测量法最简单的方法是具有透射几何结构的宽场干涉显微镜， 孤立性视网膜我们将测量灵长类动物神经活动产生的深度分辨光学相位变化 视网膜，并将它们用于许多视网膜神经节细胞（RGC）和其他视网膜神经节细胞的生理学表征。 神经元同时 目标2.用于视网膜活动模式反射率测量的相位分辨OCT 人类应用的下一步是相位分辨OCT;本质上，低相干干涉测量和 用于体内成像的成熟工具。我们将记录与神经元相关的光程长度变化， 使用点扫描、近红外（1060 nm）、相位分辨OCT对隔离的 灵长类视网膜 目标3.自适应光学、眼动跟踪和相位分辨OCT测量人视网膜功能 在人类中的部署需要补偿眼睛中的光学像差以及眼睛运动。 我们将开发一个系统，使用AOSLO成像视网膜的眼睛跟踪，有针对性地提供刺激 光和OCT探头的定位。我们将在人类身上测试这一系统并展示其潜力 在临床环境中的应用。

项目成果

Reply to Farrell: Experimental evidence is the ultimate judge for model assumptions.

回复法雷尔：实验证据是模型假设的最终判断。

• DOI: 10.1073/pnas.2017702117
• 发表时间: 2020
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Ling,Tong;Boyle,KevinC;Palanker,Daniel
• 通讯作者: Palanker,Daniel