Validated Autofluorescence in Age-Related Macular Degeneration

 描述（由申请人提供）：对年龄相关性黄斑变性（AMD）的理解和治疗正在经历一场革命，AMD是发达国家致盲的主要原因。眼内注射药物，可以阻止快速破坏性的“湿”形式的疾病已经改变了这种形式的慢性，可管理的疾病。现在，我们正面临着“干性”或萎缩性AMD形式的挑战，这种形式的AMD进展得更慢，但其进展到地图状萎缩（GA）的晚期形式充其量只能被目前的口服抗氧化剂疗法阻止，但不能停止。这项研究的广泛目标是更好地统一了解干性AMD的生物化学和结构成分，在活体眼睛中并在实验室中验证，这反过来将导致根本原因和治疗。关于干性AMD和GA的发病机制的理论很多，但都不确定。视网膜色素上皮细胞（RPE）是视网膜下重要细胞层，对视网膜营养、氧气供应和视觉功能至关重要。因此，RPE健康可能在AMD中发挥作用是合乎逻辑的。幸运的是，有一种非侵入性的成像技术可以用来研究RPE，称为“自体荧光”（AF），这种技术在临床和研究环境中得到了越来越多的使用。其基本原理是，视网膜色素上皮含有一种称为“脂褐质”的物质，该物质在蓝光下发出荧光，产生可被检测和映射的橙子辉光。最近，成像仪器已经被修改用于研究，通过插入荧光参考芯片，其允许量化AF信号（qAF成像），从而提供脂褐质的量和分布的生化测定。因此，这些数量和模式可以在正常受试者和AMD患者之间以及在不同时间直接进行比较。特别是，这些图像是干性AMD早期阶段和这些阶段进展到GA的RPE的优秀图片。另一种快速发展的技术被称为“谱域光学相干断层扫描”（SD-OCT）。它提供活体视网膜、RPE和下层脉络膜的高分辨率结构图像。该提案的具体目标包括将qAF的生物化学和SD-OCT的结构精度结合起来，以了解随着AMD的进展，RPE和视网膜的相互作用。病理学实验室的天才合作者将通过识别活体患者图像中看到的确切解剖结构，指导研究工作，对患有相同阶段AMD的供体眼睛进行平行研究。这项事业的成功将为受苦的病人带来急需的救济，并减轻老龄化人口的医疗保健负担。

 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.