Investigating fundamental properties and clinical applications of the optoretinogram

研究视视网膜图的基本特性和临床应用

• 批准号: 10357416
• 负责人: Ravi S. Jonnal
• 金额: $ 37.28万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10357416
• 关键词: 3-Dimensional; Affect; Age related macular degeneration; Animal Model; Biochemical; Biochemical Process; Biological Assay; Blindness; Brain; Cells; Characteristics; Clinic; Clinical; Clinical Trials; Complex; Data; Data Analyses; Dependence; Development; Disease; Duct (organ) structure; Early Diagnosis; Electroretinography; Feedback; Functional disorder; Genetic Models; Goals; Grant; Health; Human; Image; Interneurons; Lead; Light; Measurable; Measurement; Measures; Methods; Microscopic; Morphology; Mutation; Natural experiment; Neuronal Dysfunction; Neurophysiology - biologic function; Noise; Optical Coherence Tomography; Optics; Pathologic; Pathology; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Photons; Photoreceptors; Physiology; Property; Proteins; Public Health; Reproducibility; Resolution; Rest; Retina; Retinal Diseases; Rod Outer Segments; Sampling; Secondary to; Sex Differences; Signal Transduction; Source; Stimulus; Techniques; Technology; Testing; Three-Dimensional Image; Tissues; Transducin; Translations; Variant; Vertebrate Photoreceptors; Visual Acuity; Work; adaptive optics; age effect; base; cell injury; clinical application; clinical imaging; design; disorder of macula of retina; genetic testing; geographic atrophy; improved; inherited retinal degeneration; interest; mouse model; novel; response; retinal neuron; tool

Abstract This grant will investigate the optoretinogram (ORG)–an experimental, all optical assay of human photoreceptor function–and its potential to reveal dysfunction at the cellular level. The ORG is based on adaptive optics optical coherence tomography (AO­OCT), which is the only existing way to produce 3D images of the living human retina with cellular resolution. It leverage our novel observation that light stimuli cause microscopic deformations in the living photoreceptor outer segment (OS), along with OCT’s sensitivity to deformations in the tissue much smaller than the wavelength of the imaging source. Aim 1 investigates the ORG’s ability to measure function in rods and cones, by measuring responses in normal subjects and characterizing the signal’s sensitivity to changes in stimu­ lus energy, and factors affecting this sensitivity, such as spatial and temporal variance in response, computational factors, and photon noise. Aim 2 investigates the mechanisms underlying light­evoked OS deformation. We will rigorously determine the light levels at which the deformations are saturated, the effect of multiple flashes, and the signal’s dependence on retinal eccentricity, all of which provide valuable information about the biochemical processes causing the observed deformations. Aim 3 applies the ORG to well­characterized retinal disease, to determine whether it is able to detect pathological dysfunction in photoreceptors suffering from known deficits. Well­characterized deficits, in turn, offer natural experiments which may shed light on the biochemical and biome­ chanical determinants of the observed light­evoked deformations in the OS.

摘要 这笔赠款将研究视网膜图(ORG)--一种实验性的、全光学的人类光感受器分析方法 功能--及其在细胞水平上揭示功能障碍的可能性。ORG是基于自适应光学的 相干断层扫描(AOCT)，这是目前唯一一种产生活体人类视网膜3D图像的方法 具有细胞分辨率。它充分利用了我们新的观察结果，即光刺激会导致大脑中 活的光感受器外段(OS)，以及OCT对组织变形的敏感度要小得多 而不是成像光源的波长。目标1调查ORG测量杆和杆中功能的能力 通过测量正常受试者的反应和表征信号对刺激变化的敏感性 LUS能量，以及影响这种敏感度的因素，例如响应的空间和时间变化，计算 因子和光子噪声。目的2研究光引起的OS变形的机制。我们会 严格确定变形达到饱和时的灯光级别、多次闪烁的效果以及 信号对视网膜偏心率的依赖性，所有这些都提供了关于生物化学的有价值的信息 导致观测到的变形的过程。目标3将ORG应用于具有良好特征的视网膜疾病，以 确定它是否能够检测出患有已知缺陷的光感受器的病理功能障碍。 反过来，特征明确的缺陷提供了自然实验，这些实验可能会揭示生化和生物组 观察到的光引起的OS变形的机械决定因素。