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: 10553620
• 负责人: Ravi S. Jonnal
• 金额: $ 39.05万
• 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/10553620
• 关键词: 3-Dimensional; Affect; Age related macular degeneration; Animal Model; Biochemical; Biochemical Process; Biological Assay; Biomechanics; Blindness; Brain; Cells; Characteristics; Clinic; Clinical; Clinical Trials; Complex; Data; Data Analyses; Dependence; Development; Disease; Early Diagnosis; Electroretinography; Experimental Designs; 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; Osmosis; Pathologic; Pathology; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Photons; Photoreceptors; Physiology; Property; Proteins; Public Health; Recommendation; 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; 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; structural imaging; 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.

抽象的 该赠款将研究Optoretogron（ORG） - 一种实验，所有的光学测定 功能及其在细胞水平上揭示功能障碍的潜力。该组织基于自适应光学光学 相干断层扫描（AOOCT），这是生产人类视网膜3D图像的唯一方法 与细胞分辨率。它利用了我们的新发现，即光刺激在 活体感受器外部段（OS），以及OCT对组织中变形的敏感性 比成像源的波长。 AIM 1调查了组织在杆中测量功能的能力， 锥，通过测量正常受试者的反应并表征信号对刺激变化的敏感性 LU能量以及影响这种灵敏度的因素，例如响应中的空间和临时方差，计算 因素和光子噪声。 AIM 2研究了Light Evering OS变形的基础机制。我们将 严格确定变形饱和的光级，多个闪光的效果以及 信号对视网膜偏心的依赖性，所有这些都提供了有关生化的宝贵信息 引起观察到的变形的过程。 AIM 3将组织应用于良好的残留疾病， 确定它是否能够检测患有已知缺陷的光感受器中的病理功能障碍。 表现良好，反过来定义了自然实验，这些实验可能会在生物化学和生物群岛上揭示 观察到的OS中观察到的浅变形的chanical决定剂。