In-vivo, High Contrast Imaging of the Human Rod Photoreceptor Mosaic

描述(由申请人提供)：目标是提高配备高分辨率自适应光学(AO)视网膜相机拍摄的杆状感光细胞马赛克的体内图像的分辨率和对比度。其他类型的细胞，如视锥细胞、视网膜色素上皮细胞和白细胞细胞的成像已经取得了巨大的成功，但到目前为止，还没有报道体内有这种视杆细胞的证据。该项目将研究先进的光学技术，这些技术可以与AO相结合，进一步提高视杆和中心凹视锥空间尺度上的视网膜图像的对比度。这些可能是先进的掩模，以抑制图像中不需要的结构，并辅以诸如使用斯泰尔斯-克劳福德效应和去卷积的方法。例如，实现这一目标将允许人们对单个视杆细胞进行计数，并计算细胞密度，然后将其与组织学测量进行比较。最初，年轻的、正常的受试者将被成像以改进和优化新的成像方法。随着工作的进展，这项研究将检查以视杆细胞为目标的疾病，如视网膜色素变性和年龄相关性黄斑变性，并将观察到的变化与标准临床测试相联系。这项工作将有助于更好地了解正常和疾病眼睛的视网膜结构。随着在动物模型中开发新的药物治疗方法，当这些治疗方法过渡到人类临床试验时，对视杆细胞的直接非侵入性成像将提供一个重要的结果衡量标准。 与公共健康相关：自适应光学(AO)已经成功地应用于人眼，以允许在活体内对视锥感光细胞进行成像。有超过1.2亿个视杆细胞与600万个视锥细胞相比，令人惊讶的是，没有报告在活着的眼睛中进行视杆成像。这里提出的工作将研究先进的光学技术来提高视锥受体图像的对比度，而且还将提供第一个杆状镶嵌的活体图像。导致全球失明的两个主要原因是视网膜色素变性(RP)和老年性黄斑变性(AMD)，它们首先出现在视杆受体上。一旦完成，这项工作将对我们理解这些疾病如何影响视网膜结构产生巨大影响，并有可能对早期疾病诊断产生影响，并将成为开发新药疗法的宝贵工具。

DESCRIPTION (provided by applicant): The goal is to enhance the resolution and contrast of in-vivo images of the rod photoreceptor mosaic taken with high resolution adaptive optics (AO) equipped retinal cameras. There has been great success in imaging other cell types such as the cones, retinal pigment epithelium and leukocytes cells but to date nobody has reported in-vivo evidence for the rods. The project will examine advanced optical techniques that can be combined with AO to further improve the contrast of the retinal images at the spatial scale of the rods and foveal cones. These may be advanced masks to suppress unwanted structure in the images complemented with approaches such as using the Stiles- Crawford effect and deconvolution. Achieving this goal will allow one, for example, to count individual rod cells and calculate cell densities which can then be compared to histological measures. Initially, young, normal subjects will be imaged to refine and optimize the new imaging approaches. As the work progresses, the study will examine diseases that target the rod cells such as retinitis pigmentosa and age related macular degeneration and relate the changes observed to standard clinical tests. This work will lead to better understanding of retinal structure in both normal and diseased eyes. With new drug treatments being developed in animal models, the direct non-invasive imaging of rod cells would provide an important outcome measure when these therapies are transitioned into human clinical trials. PUBLIC HEALTH RELEVANCE: Adaptive optics (AO) has been successfully applied to the human eye to allow imaging of cone photoreceptors in-vivo. With over 120 million rod cells compared to 6 million cones it is surprising that there are no reports of rod imaging in the living eye. The work proposed here will investigate advanced optical techniques to improve the contrast of cone receptor imagery but moreover provide the first in-vivo images of the rod mosaic. Two of the leading causes of worldwide blindness, retinitis pigmentosa (RP) and age related macular degeneration (AMD) first manifest themselves in the rod receptors. When achieved, this work will have tremendous impact into our understanding of how these diseases affect the retinal structure with the potential for earlier disease diagnosis and will be an invaluable tool in the development of new drug therapies.