Functional imaging of retinal photoreceptors

视网膜感光器的功能成像

• 批准号: 10427264
• 负责人: XINCHENG YAO
• 金额: $ 42.74万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10427264
• 关键词: Age; Age related macular degeneration; Anatomy; Animal Model; Biological Markers; Biophysical Process; Blindness; Clinical; Cone; Consumption; Custom; Detection; Diabetic Retinopathy; Disease; Early Diagnosis; Early treatment; Electron Microscopy; Evaluation; Eye; Eye diseases; Foundations; Functional Imaging; Functional disorder; Fundus photography; Grant; Human; Hybrids; Image; In Vitro; Individual; Length; Light; Measurement; Methods; Morphology; Mus; Ophthalmoscopes; Ophthalmoscopy; Optical Coherence Tomography; Optics; Phase; Photoreceptors; Phototransduction; Physiological; Physiology; Process; Resolution; Retina; Retinal Cone; Retinal Degeneration; Retinal Photoreceptors; Retinitis Pigmentosa; Rhodopsin; Rod; Sagittaria; Signal Transduction; Solid; Source; Stimulus; Structure; Testing; Time; Tissues; Vertebrate Photoreceptors; Visible Radiation; awake; base; clinical application; clinical translation; comparative; cost; design; disease diagnosis; human subject; imaging platform; in vivo; insight; light microscopy; millisecond; mouse model; prevent; quantitative imaging; recruit; response; retinal imaging; retinal rods; retinal stimulation; success; temporal measurement; therapy outcome; virtual

Project summary: This is a R01 renewal to develop functional intrinsic optical signal (IOS) imaging for physiological assessment of retinal photoreceptors. Retinal photoreceptors are known as the primary target of both age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Early detection of eye diseases and objective assessment of therapeutic outcomes are essential steps to prevent vision loss and blindness. Structural only biomarkers cannot provide enough information for evaluating physiological condition of retinal photoreceptors, and combined functional test is frequently required for disease detection and treatment assessment. However, it is time-consuming and costly inefficient to conduct separate structural and functional measurements. Functional IOS imaging, also termed as optoretinography (ORG) or optophysiology, is based on near infrared (NIR) light mapping of stimulus-evoked physiological activities in the retina. Because IOS imaging is based on dynamic processing of retinal images, it can naturally provide structural information offered in traditional fundus photography. During the first grant period, we have demonstrated stimulus evoked IOS response at the outer segment of retinal photoreceptors. The fast photoreceptor-IOS occurs immediately after the onset of the retinal stimulation, differentiating itself from timely delayed IOS changes at the inner retina. The fast photoreceptor-IOS provides a unique marker for objective ORG of photoreceptor physiology, without signal contamination of post-photoreceptor layers. We propose here to characterize biophysical mechanism of the fast photoreceptor-IOS (aim 1); and validate fast photoreceptor-IOS imaging for objective ORG of photoreceptor function in human subjects (aim 2). The first aim is to use animal models to verify the correlation of the fast photoreceptor-IOS to the activation phase of phototransduction. A custom-designed hybrid confocal-OCT ophthalmoscope will be used for in vivo characterization of fast photoreceptor-IOS in WT and rd10 mice. In vitro time-lapse light microscopy will be conducted to characterize transient outer segment response in individual photoreceptors. Comparative electron microscopy of dark- and light-adapted retinal tissues will be implemented to verify light-driven outer segment shrinkage at sub-disc level. The second aim is to verify the feasibility of clinical translation of using fast photoreceptor-IOS imaging for in vivo ORG of human photoreceptors. We have recently demonstrated virtually structured detection (VSD) based super-resolution imaging of individual rods and cones in awake human. During this project, the VSD based super-resolution ophthalmoscopy will be refined to achieve µm level spatial-resolution and ms level temporal-resolution for imaging fast photoreceptor-IOS changes in human photoreceptors. Success of this study will pave the way towards pursuing clinical application of objective ORG of retinal photoreceptors, enabling early disease diagnosis and prompt treatment assessment of AMD, RP and other eye problems which can cause photoreceptor dysfunctions.

项目摘要：这是R01的续订，用于开发功能性固有光学信号（iOS）成像 视网膜光感受器的生理评估。视网膜感受器被称为 年龄相关的黄斑变性（AMD）和色素性视网膜炎（RP）。早期发现眼病 对治疗结果的客观评估是防止视力丧失和失明的重要步骤。 结构性仅生物标志物无法提供足够的信息来评估视网膜的物理状况 疾病检测和治疗经常需要光感受器和联合功能测试 评估。但是，进行单独的结构和功能是耗时且昂贵的效率高效 测量。功能性iOS成像，也称为OptoteInography（org）或光生理学，是基于 视网膜中刺激诱发的生理活性的近红外（NIR）映射。因为iOS成像 基于视网膜图像的动态处理，它自然可以提供提供的结构信息 传统的眼底摄影。在第一个赠款期间，我们已经证明了iOS的刺激 视网膜光感受器的外部段的响应。快速感受器-IOS发生在 视网膜刺激的开始，将自己与及时延迟iOS变化区分开。这 快速光感受器-IOS为光感受器生理的目标组织提供了独特的标记，没有信号 后感受器层的污染。我们在这里建议表征快速的生物物理机制 感受器-IOS（AIM 1）;并验证光感受器物镜的快速感受器-IOS成像 在人类受试者中的功能（AIM 2）。第一个目的是使用动物模型来验证快速的相关性 光感受器-IOS到光转导的激活阶段。定制设计的混合动力共同OCT 眼镜镜将用于在WT和RD10小鼠中快速光感受器-IOS的体内表征。体外 将进行延时光学显微镜，以表征个体的瞬态外部段响应 感受器。将实施深色和光适应视网膜组织的比较电子显微镜 验证以下盘级的光驱动外部段收缩。第二个目的是验证 使用快速感光体-IOS成像用于人类感光体的体内组织的临床翻译。我们有 最近证明了基于几乎结构化检测（VSD）的单个杆的超分辨率成像， 清醒人的锥。在此项目期间，基于VSD的超分辨率眼镜检查将完善 实现µM水平的空间分辨率和MS水平临时分辨率，用于成像快速感光体变化 在人类感受器中。这项研究的成功将为追求临床应用的方式铺平 视网膜光感受器的目标组织，使早期疾病诊断和及时的治疗评估 AMD，RP和其他眼睛问题，可能引起感光受体功能障碍。