Interferometric optophysiology of the human retina.

人类视网膜的干涉光生理学。

• 批准号: 8912810
• 负责人: Austin Roorda
• 金额: $ 70.17万
• 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 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912810
• 关键词: Address; Animal Model; Biological Neural Networks; Blindness; Cell membrane; Cells; Clinical; Collaborations; Cone; Coupling; Diagnosis; Disease; Electrodes; Electrophysiology (science); Eye; Eye Movements; Fluorescence; Functional disorder; Generations; Geometry; Glaucoma; Goals; Human; Image; In Vitro; Indium; Individual; Interferometry; Investigation; Ions; Lasers; Lateral; Length; Life; Light; Maps; Measurable; Measurement; Measures; Membrane; Methods; Microscopy; Monitor; Natural regeneration; Neurons; Ophthalmology; Ophthalmoscopy; 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; 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 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（由适用提供）：我们的目标是开发一种新技术，用于对单个视网膜神经元的活性及其在活的人类视网膜中的蜂窝分辨率下的光驱动输入。如果成功，该技术将为了解和监测视网膜疾病的治疗提供一种全新的客观方法，从而改变眼睛和视力的科学研究。该项目直接解决了RFA-EY-14-001中概述的优先事项，这是Nei Audacious目标计划中的第一个RFA。拟议的工作依赖于结合和验证两种新方法。首先，原则上可以使用干涉法（包括分辨的OCT；在UC Riverside的公园实验室）来测量在膜去极化和离子影响过程中发生的细胞膜中的纳米尺度扭曲。通过深度分辨率，这些测量值将使我们能够在整个视网膜的层次，在细胞分辨率下非侵入性地测量神经活动。其次，自适应光学扫描激光眼镜检查（UC Berkeley的Roorda Lab）和基于图像的眼睛跟踪可用于通过克服光学差异和眼神抖动的蜂窝精度在视网膜上刺激和测量光束。该技术将使我们能够在体内激活具有可见光的单个光感受器和具有可见光的光感受器的基团。要推进和结合这些方法，需要逐步进行技术聚集。在一次独特的合作中，我们将建立在孤立的视网膜（斯坦福大学的Palanker Lab）中对更简单的宽场干涉测量，并结合大型的多种电磁体物理测量，在灵长类动物视网膜（斯坦福大学的Chichilnisky Lab）中，以验证和调用光学测量。最终，每个步骤的创新形成了一个强大的工具，独立或结合了其他方法，并发现适用于光学成像，视网膜生理，心理物理学和临床眼科。具体目的是：目标1。在神经信号传导过程中灵长类动物视网膜去极化中测量神经元活性模式的宽场干扰会产生可检测到干扰的细胞中的纳米尺度变形。最简单的方法是在孤立的视网膜中使用传输几何形状的宽场干涉测量显微镜。我们将测量由灵长类动物视网膜中神经活动产生的深度分解的光相变化，并将其用于许多视网膜的物理特征 神经节细胞（RGC）和其他视网膜神经元。 AIM 2。相位分辨的OCT用于视网膜活性模式的反射率测量。下一步迈进了人类应用的是相位分辨的OCT；从本质上讲，低氧化干扰和体内成像的建立良好的工具。我们将使用点扫描，近IIR（1060 nm），在孤立的原代视网膜上进行相位分辨的OCT，记录与神经元活性相关的光路长度变化。 AIM 3。用于测量人类视网膜功能的自适应光学元件，眼科跟踪和相位分辨的OCT。在人类中的部署需要补偿眼睛中的光差以及眼动。我们将开发一个系统，该系统使用AOSLO对视网膜进行映像进行眼睛跟踪，刺激光的靶向输送以及OCT探针的定位。我们将在人类中测试该系统，并证明其在临床环境中的潜在应用。