Tracking change in rod, cone, and RPE mosaics independently in geographic atrophy

描述（由申请人提供）：年龄相关性黄斑变性是55岁以上人群严重视力损害的最常见原因（Adler, Curcio, Hicks, Price, & Wong, 1999; Friedman et al., 2004）。地理萎缩是老年性黄斑变性的晚期，目前尚无治疗方法。随着未来十年美国人口的老龄化，地理萎缩的个体数量预计将增加50% （Friedman et al., 2004）。这种疾病的病因尚不清楚，这阻碍了治疗方法的发展。视网膜中的几种细胞类型与地理萎缩有关，但目前的临床工具不可能检查这些细胞在活体人眼中经历的微观变化。高分辨率视网膜成像方法使用自适应光学，一种测量和校正所有眼睛中存在的光学像差的方法，允许对活体人类视网膜中的单个细胞进行显微镜检查。本项目的目的是将高分辨率视网膜成像与自适应光学应用于地理萎缩患者，同时成像视网膜中三个独立的细胞嵌合：视锥细胞、视杆细胞和视网膜色素上皮细胞，并随着疾病的进展跟踪它们。对光敏杆状和锥状光感受器以及视网膜色素上皮（另一种对视力至关重要的视网膜细胞类型）的高分辨率视网膜成像将使我们能够看到由于地理萎缩而导致的微观变化，这在活人眼睛中从未见过。该项目将深入了解地理萎缩是如何通过这些细胞类型进行的，包括细胞损失的顺序，这将使我们能够区分关于地理萎缩起源的不同竞争理论。这种理解对于针对地理萎缩的治疗干预针对适当的细胞类型至关重要。自适应光学成像方法的应用不仅可以使我们区分地理萎缩的不同理论，还可以提供一种在其时间过程中更早地检测疾病的方法，并最终可能为地理萎缩疗法的发展提供有价值的结果测量。[在AOSLO中使用高分辨率视网膜密度测量，我们将评估伴随地理萎缩的结构变化的光感受器功能的变化。]

DESCRIPTION (provided by applicant): Age-related macular degeneration is the most common cause of severe visual impairment in individuals over the age of fifty-five (Adler, Curcio, Hicks, Price, & Wong, 1999; Friedman et al., 2004). Geographic atrophy is an advanced stage of age-related macular degeneration that currently has no treatment. As the US population ages over the next decade, the number of individuals with geographic atrophy is expected to increase by fifty percent (Friedman et al., 2004). The cause of the disease is not understood, which is impeding the development of treatments for it. Several cell types in the retina have been implicated in geographic atrophy, but it is impossible to examine the microscopic changes that these cells undergo in the living human eye using current clinical tools. High resolution retinal imaging methods, which use adaptive optics, a method for measuring and correcting the optical aberrations present in all eyes, allow for microscopic examination of individual cells in the living human retina. The objective of this project is to apply high resolution retinal imaging with adaptive optics to geographic atrophy patients to simultaneously image three independent cell mosaics in the retina: cones, rods and retinal pigment epithelium, and to track them as the disease progresses. High resolution retinal imaging of the light sensitive rod and cone photoreceptors and of the retinal pigment epithelium (another retinal cell type that is critical to vision) will allow us to see microscopic changes due to geographic atrophy that have never before been seen in the living human eye. This project will provide insight into how geographic atrophy progresses through these cell types, including the sequence of cell loss, which will allow us to discriminate between different competing theories regarding the origin of geographic atrophy. This understanding will be critical for targeting therapeutic interventions for geographic atrophy to the appropriate cell type. Not only may the application of adaptive optics imaging methods allow us to discriminate between different theories of geographic atrophy, it may also provide a way to detect the disease earlier in its time-course and eventually may provide a valuable outcome measure for the development of therapies for geographic atrophy. [Using high resolution retinal densitometry in AOSLO, we will assess changes in photoreceptor function that accompany structural changes in geographic atrophy.] PUBLIC HEALTH RELEVANCE: Geographic atrophy is an advanced stage of age-related macular degeneration, a disease that is the most common cause of severe visual impairment in individuals over the age of fifty-five. This project aims to develop a comprehensive understanding of the origin of geographic atrophy and its progression by using advanced imaging methods to see how different cells in the eye are changed as a result of disease. This understanding is critical for the development of treatments for geographic atrophy, a disease that is expected to affect more Americans as the population ages.