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

描述（由申请人提供）：视网膜相关性黄斑变性是年龄超过55岁的个体中严重视力损害的最常见原因（Adler，Curcio，Hicks，Price，& Wong，1999; Friedman等人，2004年）。地图状萎缩是年龄相关性黄斑变性的晚期，目前尚无治疗方法。随着美国人口在未来十年内老龄化，预计患有地图状萎缩的个体数量将增加50%（Friedman等人，2004年）。视网膜地图状萎缩的病因尚不清楚，这阻碍了治疗方法的发展。视网膜中的几种细胞类型与地图状萎缩有关，但使用目前的临床工具无法检查这些细胞在活体人眼中经历的微观变化。使用自适应光学的高分辨率视网膜成像方法，一种用于测量和校正存在于所有眼睛中的光学像差的方法，允许对活体人类视网膜中的单个细胞进行显微镜检查。该项目的目的是将具有自适应光学的高分辨率视网膜成像应用于地图状萎缩患者，以同时成像视网膜中的三个独立细胞镶嵌：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。高分辨率视网膜成像的光敏感杆和锥光感受器和视网膜色素上皮细胞（另一种视网膜细胞类型，是至关重要的视觉）将允许我们看到微观变化，由于地图萎缩，从来没有见过在活的人的眼睛。该项目将提供深入了解地图状萎缩如何通过这些细胞类型进展，包括细胞损失的顺序，这将使我们能够区分关于地图状萎缩起源的不同竞争理论。这种理解对于将地图状萎缩的治疗干预靶向到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图状萎缩的不同理论，它也可以提供一种方法来检测疾病的早期在其时间过程中，并最终可能提供一个有价值的结果测量地图状萎缩的治疗方法的发展。[在AOSLO中使用高分辨率视网膜密度测定，我们将评估伴随地图状萎缩结构变化的感光器功能变化。] 公共卫生相关性：地图状萎缩是年龄相关性黄斑变性的晚期阶段，年龄相关性黄斑变性是55岁以上个体中严重视力损害的最常见原因。该项目旨在通过使用先进的成像方法来全面了解地图状萎缩的起源及其进展，以了解眼睛中的不同细胞如何因疾病而发生变化。这种理解对于地图状萎缩的治疗方法的发展至关重要，随着人口老龄化，这种疾病预计将影响更多的美国人。

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.