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

描述（由申请人提供）：目标是通过配备高分辨率自适应光学（AO）的视网膜相机，提高杆状光感受器镶嵌的体内图像的分辨率和对比度。在其他细胞类型，如视锥细胞、视网膜色素上皮细胞和白细胞的成像方面已经取得了巨大的成功，但到目前为止，还没有人报道过视杆细胞的活体证据。该项目将研究可以与AO结合的先进光学技术，以进一步提高视杆细胞和中央凹视锥细胞空间尺度上视网膜图像的对比度。这些可能是高级掩模，以抑制图像中不需要的结构，并辅以诸如使用斯蒂尔斯-克劳福德效应和反卷积等方法。实现这一目标将允许人们，例如，计数单个杆状细胞和计算细胞密度，然后与组织学测量进行比较。首先，将对年轻的正常受试者进行成像，以完善和优化新的成像方法。随着工作的进展，该研究将检查针对杆状细胞的疾病，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试验联系起来。这项工作将有助于更好地了解正常和病变眼睛的视网膜结构。随着新的药物治疗方法在动物模型上的发展，当这些治疗方法过渡到人类临床试验时，对杆状细胞的直接非侵入性成像将提供一个重要的结果测量。

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.