Validated Autofluorescence in Age-Related Macular Degeneration

 描述(申请人提供)：对老年性黄斑变性(AMD)的认识和治疗正在经历一场革命，AMD是发达国家导致失明的主要原因。眼内注射药物可以阻止这种快速破坏性的“湿”形式的疾病，已经将这种形式改变为一种慢性的、可控的疾病。现在我们正面临着“干性”或萎缩型AMD的挑战，这种疾病进展较慢，但目前口服抗氧化剂的治疗充其量只能阻止而不是阻止其发展为晚期的地理萎缩(GA)。这项研究的广泛目标是更好和统一地了解干性AMD的生化和结构成分，在活着的眼睛中，并在实验室中得到验证，这反过来将导致根本原因和治疗。干性AMD和GA的发病机制有很多理论，但没有一个是确定的。许多人共有的一个线索涉及视网膜色素上皮(RPE)，这是视网膜下面的一层重要细胞，对其营养、氧气供应和视觉功能至关重要。因此，RPE健康状况可能在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，这种技术被称为“自体荧光”(AF)，正在临床和研究环境中得到广泛应用。其基本原理是RPE含有一种名为“脂褐素”的物质，这种物质在蓝光下发出荧光，产生可被探测和测绘的橙色光。最近，成像仪器为了研究而进行了改进，插入了一个荧光参考芯片，允许量化房颤信号(QAF成像)，从而提供了脂褐素的数量和分布的生化分析。因此，这些数量和模式可以直接在正常受试者和AMD患者之间进行比较，并跨越时间。特别是，这些图像是RPE在干性AMD早期阶段以及随着这些阶段进展到GA的极佳图片。另一种快速发展的技术是光谱域光学相干层析成像(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。这项建议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，以了解随着AMD的进展，RPE和视网膜的相互作用。病理实验室中有天赋的合作者将通过识别活体患者图像中所见的准确解剖结构，指导对AMD相同阶段的供体眼睛进行平行研究。这一项目的成功将为遭受痛苦的患者带来亟需的缓解，并减轻老龄化人口的医疗负担。

 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.