OCT-based functional biomarkers for degenerative diseases of the photoreceptor-RPE-choroid neurovascular unit

基于 OCT 的光感受器-RPE-脉络膜神经血管单元退行性疾病的功能生物标志物

• 批准号: 10737548
• 负责人: Ravi S. Jonnal
• 金额: $ 60.02万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737548
• 关键词: Affect; Age; Age related macular degeneration; Angiography; Atrophic; Biological Markers; Blindness; Bruch' s basal membrane structure; Cells; Choroid; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Complement; Data; Degenerative Disorder; Deposition; Development; Disease; Disease Progression; Drusen; Dryness; Electroretinography; Equipment; Eye; Eye Movements; Feedback; Functional disorder; Genes; Geographic Locations; Goals; Grant; Health; Human; Image; Industrialization; Knowledge; Length; Lesion; Light; Location; Measurement; Measures; Methods; Modification; Morphology; Motivation; Mutation; Neuronal Dysfunction; Neurophysiology - biologic function; Noise; Optics; Outcome Measure; Pathogenicity; Patients; Persons; Pharmaceutical Preparations; Phase; Photoreceptors; Phototransduction; Physiological; Play; Protocols documentation; Recommendation; Recovery; Research; Resolution; Retina; Retinal Diseases; Retinitis Pigmentosa; Role; Sequence Analysis; Signal Transduction; Source; Stargardt' s disease; Stimulus; Structural defect; System; Technology; Testing; Thick; Time; Translating; Treatment Efficacy; Visual Acuity; Visual Fields; Visualization; Work; adaptive optics; clinical imaging; computing resources; cost; density; design; field study; functional loss; geographic atrophy; image processing; imaging Segmentation; imaging system; improved; inherited retinal degeneration; neurovascular unit; next generation; novel; novel marker; novel strategies; operation; patient population; potential biomarker; research clinical testing; response; retinal neuron; signal processing; standard care; statistics; structural imaging; visual cycle; volunteer

OCT-based functional biomarkers for degenerative diseases of the photoreceptor-RPE-choroid neurovascular unit Abstract: Important diseases of the photoreceptor-RPE-choroid neurovascular unit include age-related macular degeneration (AMD), retinitis pigmentosa (RP), and other inherited retinal degenerations (IRDs). The number of people with AMD worldwide is nearly 200 million, and expected to approach 300 million over the next twenty years, while IRDs affect more than 5 million more. AMD is the leading cause of blindness in the industrialized world, and also the leading cause of blindness among people over the age of 60. Standard treatments exist for neither the more prevalent dry form of AMD nor IRDs, and key obstacles to discovering them are 1) limited understanding of the pathogenic steps leading to vision loss; and 2) lack of biomarkers for disease progression and recovery. In recent years our team has pioneered the emerging field of optoretinography (ORG) using adaptive optics (AO) and OCT. The ORG is an all-optical, noninvasive, objective measure of neural function in the retina, and has the potential to yield new functional biomarkers of retinal disease. Due to the cost and complexity of AO-OCT imaging systems and their subsequent scarcity, ORG measurements have been made only in small numbers of volunteers, mostly without retinal disease. We propose to develop a next-generation, proto-clinical ORG system and characterize its sensitivity, dynamic range, and spatial resolution. First, we will test a number of modifications to the protocols for imaging and signal processing, with a focus on improving the clinical utility of the method. Second, in healthy subjects and several patient populations we will measure ORG responses, along with other OCT-based measurements such as structural OCT imaging and OCTA. The patient populations to be studied are: 1) IRD patients including those with Stargardt’s disease and retinitis pigmentosa; 2) intermediate AMD patients with drusen, subretinal drusenoid deposits, and/or hyperreflective foci; and 3) late AMD patients with regions of geographic atrophy. The motivations for these patient populations are 1) to test hypotheses about the mechanisms underlying the ORG response, and 2) to demonstrate the ORG’s capacity to detect and quantify disease-related dysfunction. The proposed work will result in 1) a clinically useful ORG platform (also capable of structural and angiographic imaging), and 2) new knowledge that will permit us to design ORG- and OCT-based biomarkers for retinal disease that relate to mechanisms of action and have characterized sensitivity to photoreceptor dysfunction.

基于OCT的功能性生物标志物，用于光感受器-RPE-挥主的退行性疾病 神经血管单元 摘要：光感受器-RPE-舌神经血管单元的重要疾病包括与年龄相关的黄斑 变性（AMD），色素性视网膜炎（RP）和其他遗传性视网膜变性（IRDS）。人数 在全球范围内，AMD近2亿，预计未来20年将接近3亿，而IRD 影响超过500万。 AMD是工业化世界中失明的主要原因，也是领先的 60岁以上人群失明的原因。不存在更普遍的干燥形式的标准治疗 AMD或IRD，发现它们的关键障碍是1）对导致致病步骤的理解有限 视力丧失； 2）缺乏疾病进展和康复的生物标志物。近年来，我们的团队开创了 使用自适应光学器件（AO）和OCT的optoretography（org）新兴领域。该组织是一个全面的，无创的， 视网膜中神经元功能的客观测量，并且有可能产生视网膜的新功能生物标志物 疾病。由于AO-O-OCT成像系统的成本和复杂性及其随后的稀缺性，ORG测量值 仅在少数志愿者中制作，主要没有残留疾病。我们建议开发一个 下一代，原始临床组织系统，并表征其灵敏度，动态范围和空间分辨率。第一的， 我们将对用于成像和信号处理的协议进行许多修改，重点是改进 该方法的临床实用性。第二，在健康受试者和几个患者人群中，我们将衡量组织反应， 以及其他基于OCT的测量值，例如结构OCT成像和八八。病人的人数为 Studiod是：1）IRD患者，包括患有Stargardt疾病和视网膜炎的患者； 2）中级AMD 患有drusen，视视网膜下沉积物和/或过度反射灶的患者； 3）晚期AMD患者 地理萎缩。这些患者人群的动机是1）测试有关机制的假设 ORG响应的基础，以及2）证明组织检测和量化疾病相关的能力 功能障碍。拟议的工作将导致1）临床上有用的组织平台（还具有结构性和 血管造影成像）和2）新知识将使我们能够设计基于ORG和OCT的生物标记物以剩余 与作用机理有关的疾病，并表征了对光感受器功能障碍的敏感性。