Validated Autofluorescence in Age-Related Macular Degeneration

经验证的自发荧光在年龄相关性黄斑变性中的作用

• 批准号: 9135429
• 负责人: Roland THEODORE SMITH
• 金额: $ 12.54万
• 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 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9135429
• 关键词: Address; Age related macular degeneration; Aging; Animal Model; Antioxidants; Area; Atrophic; Benign; Biochemical; Biochemistry; Biological Assay; Blindness; Cell Count; Cell Death; Cells; Cellular Morphology; Choroid; Chronic; Clinical; Clinical Research; Color; Confocal Microscopy; Country; Cross-Sectional Anatomy; Cytoplasmic Granules; Data; Data Set; Deposition; Diffuse; Disease; Drusen; Exudative age-related macular degeneration; Eye; Fundus; Goals; Hand; Health; Healthcare; Histology; Histopathology; Human; Image; Imaging Device; Imaging Techniques; Imaging technology; Injection of therapeutic agent; Knowledge; Laboratories; Lead; Lesion; Life; Light; Link; Lipofuscin; Lobule; Maps; Measures; Modeling; Molecular; Morphology; Optical Coherence Tomography; Oral; Oranges; Oxygen; Pathogenesis; Pathology; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Photography; Photoreceptors; Pigments; Plant Roots; Play; Protocols documentation; Recording of previous events; Research; Resolution; Retina; Retinal; Role; Scanning; Signal Transduction; Staging; Structure; Structure of retinal pigment epithelium; Technology; Testing; Time; Variant; Vision; Visual; aging population; base; crosslink; density; extracellular; fluorophore; geographic atrophy; improved; in vivo; instrumentation; macula; non-invasive imaging; nutrition; outcome forecast; patient population; retinal rods; risk variant; spatiotemporal; success; theories

 DESCRIPTION (provided by applicant): The understanding and treatment of age-related macular degeneration (AMD), the leading cause of blindness in the developed world, is undergoing a revolution. Intraocular injections of medications that can arrest the rapidly destructive "wet" form of the disease have changed this form to a chronic, manageable illness. Now we are facing the challenge of the "dry," or atrophic, form of AMD that proceeds more slowly but whose progression to the advanced form of geographic atrophy (GA) is at best impeded, but not stopped, by current therapies of oral antioxidants. The broad goal of this research is a better and unified understanding of the biochemical and structural components of dry AMD, in the living eye and validated in the laboratory, that in turn will lead to the root causs and treatment. Theories of the pathogenesis of dry AMD and GA abound, but none are certain. One thread common to many involves the retinal pigment epithelium (RPE), an important layer of cells just under the retina that are critical to its nutrition, oxygen supply, and visual functins. Hence, it is logical that RPE health may play a role in AMD. Fortunately, there is a non-invasive imaging technique with which to study the RPE called "autofluorescence" (AF), which is gaining in use in clinical and research settings. The basic principle is that the RPE contains a substance called "lipofuscin" which fluoresces under blue light to produce an orange glow that can be detected and mapped. Very recently, the imaging instrument has been modified for research by inserting a fluorescent reference chip that allows the AF signal to be quantified (qAF imaging), thereby providing a biochemical assay of the amounts and distribution of lipofuscin. Hence, these quantities and patterns can be directly compared, between normal subjects and patients with AMD, and across time. In particular, these images are excellent pictures of the RPE in the early stages of dry AMD and as these stages progress to GA. Another rapidly advancing technology is called "spectral domain optical coherence tomography" (SD- OCT). It provides high-resolution structural images of the living retina, RPE, and underlying choroid. The specific aims of this proposal consist of harnessing together the biochemistry of qAF and the structural precision of SD-OCT to understand the interaction of the RPE and retina as AMD progresses over time. Gifted collaborators in the pathology lab will guide study efforts with parallel studiesof donor eyes with the same stages of AMD, by identifying the exact anatomical structures seen in images of living patients. Success in this venture will bring much-needed relief to suffering patients and relief to the healthcare burden of an aging population.

 描述（由申请人提供）：对于发达国家导致失明的主要原因——年龄相关性黄斑变性（AMD）的理解和治疗正在经历一场革命，眼内注射药物可以阻止快速破坏性的“湿性”形式。这种疾病的发展已将这种形式转变为一种慢性、可控制的疾病，现在我们面临着“干性”或萎缩性AMD的挑战，这种疾病进展较慢，但会进展为晚期的地图样萎缩。目前的口服抗氧化剂疗法充其量只是阻碍了 GA，但并没有阻止它。这项研究的总体目标是在活体眼睛中更好、统一地了解干性 AMD 的生化和结构成分，并在实验室中进行验证。 ，这反过来会导致干性 AMD 和 GA 发病机制的理论比比皆是，但许多人共同的一个线索涉及视网膜色素上皮 (RPE)，这是一层重要的细胞。因此，RPE 健康可能在 AMD 中发挥作用是合乎逻辑的，幸运的是，有一种非侵入性成像技术可以用来研究 RPE。自发荧光”（AF），这是一种在临床和研究环境中使用的物质增益。基本原理是 RPE 含有一种称为“脂褐素”的物质，它在蓝光下发出荧光，产生可检测和绘制的橙色光芒。最近,该成像仪器已针对研究进行了修改，插入了荧光参考芯片，可以量化 AF 信号（qAF 成像），从而提供脂褐素含量和分布的生化测定，因此可以直接比较这些数量和模式。 ，在正常受试者和 AMD 患者之间，特别是，这些图像是干性 AMD 早期阶段的 RPE 的出色图片，随着这些阶段发展到 GA，另一种快速发展的技术称为“谱域光学相干性”。断层扫描”（SD-OCT）。它提供活体视网膜、RPE 和底层脉络膜的高分辨率结构图像。该提案的具体目标包括综合利用 qAF 的生物化学和 SD-OCT 的结构精度来了解随着AMD随着时间的推移进展，RPE和视网膜的相互作用将通过识别AMD中所见的确切解剖结构来指导研究工作，对具有相同阶段的AMD的供体眼睛进行平行研究。这项事业的成功将为受苦的患者带来急需的救济，并减轻人口老龄化的医疗负担。