Interferometric optophysiology of the human retina.

人类视网膜的干涉光生理学。

• 批准号: 9316641
• 负责人: Austin Roorda
• 金额: $ 61.87万
• 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 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316641
• 关键词: Accelerometer; Address; Animal Model; Biological Neural Networks; Blindness; Cell membrane; Cells; Clinical; Collaborations; Cone; Coupling; Diagnosis; Disease; Electrodes; Electrophysiology (science); Elements; Eye; Eye Movements; Fluorescence; Functional disorder; Generations; Geometry; Glaucoma; Goals; Human; Image; In Vitro; Individual; Interferometry; Investigation; Ions; Lateral; Length; Light; Maps; Measurable; Measurement; Measures; Membrane; Methods; Microscopy; Monitor; Mosaicism; Natural regeneration; Neurons; Ophthalmology; Optical Coherence Tomography; Optics; Patients; Pattern; Performance; Phase; Photoreceptors; Physics; Physiological; Physiology; Positioning Attribute; Preparation; Primates; Psychophysics; Refractive Indices; Research; Resolution; Retina; Retinal; Retinal Diseases; Retinal Ganglion Cells; Retinitis Pigmentosa; Scanning; System; Technology; Testing; Tissues; Universities; Visible Radiation; Vision; Visual system structure; Work; adaptive optics; adaptive optics scanning laser ophthalmoscopy; base; electrical measurement; in vivo; in vivo imaging; innovation; nanoscale; neural patterning; neurotransmission; new technology; non-invasive imaging; novel strategies; optical imaging; phase change; public health relevance; receptive field; relating to nervous system; retinal neuron; targeted delivery; technology development; tool; transmission process; visual processing; visual stimulus

 DESCRIPTION (provided by applicant): 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 neural 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 a 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.

 描述(由申请人提供)：我们的目标是开发一种新技术，用于在活的人类视网膜中以细胞分辨率非侵入性地监测单个视网膜神经元的活动及其光驱动输入。如果成功，这项技术将提供一种全新的客观方法来了解和监测视网膜疾病的治疗，从而改变对眼睛和视力的科学研究。该项目直接涉及RFA-EY-14-001中概述的优先事项，这是NEI大胆目标倡议范围内的第一个RFA。拟议的工作依赖于结合和验证两种新方法。首先，干涉测量法(包括相分辨OCT；加州大学河滨分校的Park Lab)原则上可以用来测量细胞膜在膜去极化和离子内流过程中发生的纳米级扭曲。有了深度分辨率，这些测量将使我们能够以细胞分辨率非侵入性地测量整个视网膜各层的神经活动。其次，自适应光学扫描激光眼底镜(加州大学伯克利分校的Roorda Lab)和基于图像的眼睛跟踪可以通过克服光学像差和眼睛抖动，在活眼中以细胞精度在视网膜上定位和测量光束。这项技术将使我们能够用可见光激活单个感光器和一组感光器，同时成像体内单个下游细胞的电活动。要推进和结合这些方法，需要逐步聚合技术。在一次独特的合作中，我们将建立在对隔离视网膜电活动的更简单的广域干涉测量(斯坦福大学的Palanker实验室)的基础上，结合灵长类视网膜的大规模多电极生理测量(斯坦福大学的Chichilnisky实验室)来验证和调整光学测量。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其他方法的组合，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.在神经信号传递过程中，用于测量灵长类动物视网膜去极化的神经活动模式的广场干涉法在细胞中产生纳米级的变形，这是干涉法可以检测到的。最简单的方法是在分离的视网膜中使用透射式几何结构的广域干涉显微镜。我们将测量灵长类视网膜中神经活动产生的深度分辨光学相位变化，并将其用于许多视网膜的生理特征 神经节细胞(RGC)和其他视网膜神经元同时存在。目的2.相位分辨OCT用于视网膜活动模式的反射率测量。人类应用的下一步是相位分辨OCT；本质上，低相干度干涉测量是一种成熟的活体成像工具。我们将使用点扫描、近红外(1060 Nm)、相分辨OCT在分离的灵长类视网膜上记录与反射几何中的神经活动相关的光路长度变化。目的3.自适应光学、眼球跟踪和相位分辨OCT用于测量人体视网膜功能。在人类身上部署需要补偿眼睛的光学像差和眼睛运动。我们将开发一种使用AOSLO对视网膜进行成像的系统，用于眼睛跟踪、刺激光的定向传递和OCT探针的定位。我们将在人体上测试这一系统，并展示其在临床环境中的潜在应用。