Absolute Fundus Autofluorescence in Retinal Degenerations

视网膜变性的绝对眼底自发荧光

• 批准号: 8294753
• 负责人: Roland THEODORE SMITH
• 金额: $ 58.85万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294753
• 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' 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

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）：眼底自身荧光（AF）在我们对视网膜退行性疾病（RDD）和其他视网膜疾病的认识中起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Stargardt病（STGD）和视网膜色素变性（RP））中最早可检测到的疾病标志物之一是自体荧光成像的视网膜色素上皮（RPE）中脂褐素的异常积累。然而，目前的采集系统只提供相对AF水平，而不是脂褐素本身的生物学临界水平。我们已经组建了一个团队，包括世界权威的自体荧光成像，Francois Delori，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绝对AF测量和体内真实脂褐素水平的仪器，以推进我们对RDD的理解远远超过目前的水平。该系统是一种特殊改良的共聚焦扫描激光检眼镜（cSLO），利用我们尖端的生物医学图像分析技术，将通过量化与患者RDD病变相关的荧光，在AMD， STGD和RP的研究中创造一个范式转变。此外，我们将制造和使用类似的仪器来研究动物模型。因此，作为RDD最广泛使用的动物模型，小鼠将不再需要为了脂褐素水平而牺牲，这提供了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。自身荧光病变是回答脂褐素在AMD、STGD和RP中作用的长期悬而未决的问题的关键。绝对自身荧光成像，独特的临床可实现与所提出的设备，提供了体内的视觉，定量二维脂褐素测量。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，同时从同一设备获得视网膜结构的高分辨率光谱域光学相干断层扫描图像，以回答以下问题：脂褐素是视网膜损伤的主要原因还是其结果？通过进一步用摄影和红外图像模式登记这些扫描，并将它们与基因型和功能测试（如显微镜测量）相关联，我们将建立一个强大的数据结构，从中将产生大量新的疾病模型和假设，以在RDD中进行测试。视网膜退行性疾病对我们的人口造成了可怕的伤害，无论是年轻人还是老年人。这项新技术最终将为监测患者的进展和对包括基因治疗在内的新疗法的反应提供更坚实的基础。