Functional imaging of retinal photoreceptors

视网膜感光器的功能成像

• 批准号: 10204466
• 负责人: XINCHENG YAO
• 金额: $ 51.36万
• 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/10204466
• 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 的更新，旨在开发功能性本征光信号 (IOS) 成像 视网膜感光器的生理评估。视网膜感光细胞被称为主要目标 年龄相关性黄斑变性（AMD）和色素性视网膜炎（RP）。及早发现眼部疾病 对治疗结果进行客观评估是预防视力丧失和失明的重要步骤。 仅结构生物标志物无法提供足够的信息来评估视网膜的生理状况 疾病检测和治疗经常需要结合光感受器和功能测试 评估。然而，将结构和功能分开进行既费时又费钱，效率低下。 测量。功能性 IOS 成像，也称为视视网膜成像 (ORG) 或光生理学，基于 视网膜中刺激诱发的生理活动的近红外 (NIR) 光图。因为IOS成像 基于视网膜图像的动态处理，它可以自然地提供结构信息 传统眼底摄影。在第一个资助期间，我们展示了刺激诱发的 IOS 视网膜感光细胞外段的反应。快速光感受器-IOS 立即发生 视网膜刺激的开始，与内视网膜及时延迟的 IOS 变化不同。这 快速光感受器-IOS为光感受器生理学的客观ORG提供了独特的标记，无需信号 后感光层的污染。我们在这里建议描述快速的生物物理机制 感光器-IOS（目标1）；并验证快速感光器-IOS 成像以实现感光器的客观 ORG 在人类受试者中发挥作用（目标 2）。第一个目标是使用动物模型来验证快速的相关性 光感受器-IOS 进入光转导的激活阶段。定制设计的混合共焦 OCT 检眼镜将用于 WT 和 rd10 小鼠快速光感受器 IOS 的体内表征。体外 将进行延时光学显微镜来表征个体的瞬时外节反应 光感受器。将实施暗适应和光适应视网膜组织的比较电子显微镜检查 验证子盘级别的光驱动外段收缩率。第二个目的是验证可行性 使用快速光感受器-IOS 成像进行人类光感受器体内 ORG 的临床转化。我们有 最近展示了基于虚拟结构化检测（VSD）的单个棒的超分辨率成像 清醒的人体内的视锥细胞。在该项目期间，基于 VSD 的超分辨率检眼镜将被改进为 实现微米级空间分辨率和毫秒级时间分辨率，用于快速成像感光器 IOS 变化 在人类感光器中。这项研究的成功将为该药物的临床应用铺平道路。 视网膜光感受器的客观 ORG，实现早期疾病诊断和及时治疗评估 AMD、RP 和其他可能导致光感受器功能障碍的眼部问题。