Absolute Fundus Autofluorescence in Retinal Degenerations

视网膜变性的绝对眼底自发荧光

基本信息

批准号：
8452337
负责人：
Roland THEODORE SMITH
金额：
$ 66.28万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-15 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8452337
关键词：
Age Age related macular degeneration Animal Model Animals Area Atrophic Biochemical Biochemistry Biology Biomedical Engineering Blindness Blood Vessels Cellular biology Characteristics Choroidal Neovascularization Clinical Trials Correlation Studies Country Data Degenerative Disorder Devices Diagnosis Disease Disease Marker Disease Outcome Disease Progression Disease model Elderly Engineering Environment Eye Fluorescence Fluorescence Microscopy Fundus Future Genetic Genotype Goals Heterogeneity High Pressure Liquid Chromatography Human Image Image Analysis Individual Inflammatory Institution Laboratories Lasers Lesion Lipofuscin Macular degeneration Measurement Measures Mechanics Methods Metric Modeling Molecular Mus Natural History Ophthalmoscopes Optical Coherence Tomography Optics Outcome Measure Patient Care Patient Monitoring Patients Phenotype Pigments Play Population Positioning Attribute Prevention therapy Psychometrics Reference Standards Relative (related person)Research Resolution Resources Retina Retinal Retinal Degeneration Retinal Diseases Retinal Dystrophy Retinitis Pigmentosa Role Scanning Signal Transduction Societies Spottings Staging Standardization Stargardt&apos s disease Structure Structure of retinal pigment epithelium System Techniques Technology Testing Time Tissues Vision Vision research Work authority base bioimaging chromophore clinical care cohort cost data structure density disorder of macula of retina experience fluorophore gene therapy imaging modality improved in vivo insight instrumentation macula macular drusen mouse model neoplastic new technology parent grant photoreceptor degeneration programs prospective public health relevance response retinal damage tool development two-dimensional

项目摘要

DESCRIPTION (provided by applicant): Fundus autofluorescence (AF) plays an increasingly important role in our understanding of retinal degenerative disease (RDD) and other retinal disorders. One of the earliest detectable disease markers in age-related macular degeneration (AMD) and other retinal degenerations such as Stargardt disease (STGD) and retinitis pigmentosa (RP) is abnormal accumulation of lipofuscin in the retinal pigment epithelium (RPE) as imaged by autofluorescence. However, present acquisition systems provide only relative AF levels, not the biologically critical levels of lipofuscin itself. We have assembled a team that includes the world authority on autofluorescence imaging, Francois Delori, complementary expertise in ophthalmic instrumentation, retinal disease and imaging, retinal biology and biomedical engineering to create and systematically exploit instrumentation for absolute AF measurements and in vivo true lipofuscin levels to advance our understanding of RDD well beyond its present level. The system, a specially modified confocal scanning laser ophthalmoscope (cSLO) harnessed to our cutting edge biomedical image analysis techniques, will create a paradigm shift in the research of AMD, STGD and RP by quantifying the fluorescence associated with RDD lesions in patients. Further, we will make and use similar instrumentation to study animal models. Thus mice, the most widely used animal models for RDD, will no longer have to be sacrificed for lipofuscin levels, which offers the scientific advantage of multiple measurements from individual mice over time as well as the obvious humanitarian benefit. Autofluorescence lesions are keys to answering long-unresolved questions about the role of lipofuscin in AMD, STGD and RP. Absolute autofluorescence imaging, uniquely clinically attainable with the proposed device, offers a vision of in vivo, quantitative two dimensional lipofuscin measurements. In cohorts of these patients, we will thus perform prospective analysis of these images, acquired simultaneously with high resolution spectral domain optical coherence tomography images of retinal structure from the same device, to answer such questions as: is lipofuscin a primary cause of or does it result from retinal damage? By further registering these scans with photographic and infrared image modalities, and correlating them with genotype and functional tests such as microperimetry, we will build a powerful data structure from which will flow a host of new disease models and hypotheses to test in RDD. Retinal degenerative disease takes a terrible toll on our population, both young and old. This new technology will ultimately provide a firmer basis for monitoring patient progress and response to new therapies, including gene therapy. PUBLIC HEALTH RELEVANCE: Absolute autofluorescence imaging with a specially modified confocal scanning laser ophthalmoscope will provide, for the first time, in vivo measurements of fluorophores in retinal degenerative disease (RDD), including age-related macular degeneration. Identification of these signature compounds will be uniquely instrumental in understanding RDD, the leading cause of blindness in our country, with the insights so obtained of high value in clinical care of RDD patients, saving sight for our patients, and enormously benefiting our society.

描述（由申请人提供）：眼底自发荧光（AF）在我们对视网膜退行性疾病（RDD）和其他视网膜疾病的理解中发挥着越来越重要的作用。年龄相关性黄斑变性 (AMD) 和其他视网膜变性如斯塔加特病 (STGD) 和色素性视网膜炎 (RP) 中最早可检测到的疾病标志之一是视网膜色素上皮 (RPE) 中脂褐质的异常积累，如自发荧光成像所示。然而，目前的采集系统仅提供相对的 AF 水平，而不是脂褐素本身的生物学临界水平。我们组建了一个团队，其中包括自发荧光成像领域的世界权威 Francois Delori，以及眼科仪器、视网膜疾病和成像、视网膜生物学和生物医学工程方面的互补专业知识，以创建和系统地开发用于绝对 AF 测量和体内真实脂褐素水平的仪器，以使我们对 RDD 的理解远远超出目前的水平。该系统是一款经过特殊改造的共焦扫描激光检眼镜 (cSLO)，采用我们最先进的生物医学图像分析技术，通过量化与患者 RDD 病变相关的荧光，将在 AMD、STGD 和 RP 研究中创造范式转变。此外，我们将制造并使用类似的仪器来研究动物模型。因此，RDD 使用最广泛的动物模型小鼠将不再需要因脂褐素水平而被牺牲，这提供了随着时间的推移对单个小鼠进行多次测量的科学优势以及明显的人道主义效益。自发荧光损伤是回答脂褐素在 AMD、STGD 和 RP 中的作用这一长期未解问题的关键。绝对自发荧光成像是利用所提出的装置在临床上独特实现的，提供了体内定量二维脂褐质测量的愿景。因此，在这些患者的队列中，我们将对这些图像进行前瞻性分析，这些图像与来自同一设备的视网膜结构的高分辨率谱域光学相干断层扫描图像同时获得，以回答以下问题：脂褐素是导致这种情况的主要原因吗？视网膜损伤所致？通过进一步用摄影和红外图像模式记录这些扫描，并将它们与基因型和功能测试（例如微视野测定法）相关联，我们将构建一个强大的数据结构，从中产生大量新的疾病模型和假设，以在 RDD 中进行测试。视网膜退行性疾病给我们的年轻人和老年人带来了可怕的损失。这项新技术最终将为监测患者进展和对新疗法（包括基因疗法）的反应提供更坚实的基础。公共健康相关性：使用经过特殊改进的共焦扫描激光检眼镜进行的绝对自发荧光成像将首次提供视网膜退行性疾病（RDD）（包括年龄相关性黄斑变性）中荧光团的体内测量。这些标志性化合物的鉴定将有助于了解 RDD（我国失明的主要原因），由此获得的见解对于 RDD 患者的临床护理具有很高的价值，可以挽救我们的患者的视力，并极大地造福于我们的社会。