Investigations of Human Cone Kinetics

描述（由申请人提供）：视网膜的光感受器代表视觉的第一步。该项目将使用先进的自适应光学成像技术，以绕过眼睛光学所施加的分辨率限制，从而测量活体人类视网膜中的细胞结构和功能。使用我们实验室已经开发的技术，我们将能够以前所未有的精度探测光感受器。此外，我们将进一步开发自适应光学成像技术，以提高我们现有的成像眼睛的视杆细胞和视锥细胞的能力，目标是在单个受试者会话中成像后极大区域中的每个感光细胞。这将使用双波长成像来实现，其中我们使用近红外光以高对比度对视锥进行成像，并使用同时获取的低强度可见光图像通过图像平均来提供视杆细胞和视锥细胞的更高分辨率图像。使用较低强度的可见光的能力也将使我们能够直接测量眼睛中的色素沉着量，以及色素沉着量如何随着漂白和再生而变化。最后，通过使用高质量的图像来动态地引导视网膜跟踪算法，我们将使用双图像稳定技术和纯粹基于局部的探测视网膜灵敏度来探测眼睛的异常区域上的局部视网膜灵敏度。我们将使用上述技巧来问一系列具体的问题。这些问题集中在视网膜光吸收的控制，以及衰老和疾病对光感受器收集光的能力的影响。第一个问题解决了光感受器包装如何与外节中的色素沉积量相互作用以设置视锥细胞的相对吸收率。如果视锥细胞主动控制它们的量子捕获，那么在给定区域中具有较大视锥细胞的个体可能具有较低的色素光密度。与此类似，随着眼睛的老化，视网膜色素的变化也会反映出感光细胞数量的减少。在第二组实验中，我们将这种分析扩展到患有早期年龄相关黄斑病和早期地图状萎缩的患者，测试感光细胞变化的性质和程度。在最后一组实验中，我们将追踪初步数据，这些数据表明锥细胞在许多早期疾病中具有共同的表型外观。我们将检验这样一个假设，即患病但尚未死亡的视锥细胞具有共同的功能和结构外观。如果是真的，这将意味着这种变化可能是一种有效的生物标志物的视网膜视力丧失的风险和治疗效果。

DESCRIPTION (provided by applicant): The photoreceptors of the retina represent the first step of vision. This project will use advanced adaptive optics imaging techniques to bypass the resolution limits imposed by the eye's optics in order to measure cellular structure and function in the living human retina. Using the techniques already developed in our lab we will be able to probe photoreceptors with unprecedented precision. In addition, we will further develop Adaptive Optics imaging techniques to improve our existing ability to image the rod and cone photoreceptors of the eye, with the goal of imaging every photoreceptor in large regions of the posterior pole in a single subject session. This will be achieved using dual wavelength imaging where we use near infrared light to image the cones at high contrast, and use simultaneously acquired low intensities visible light images to provide higher resolution images of rods and cones through image averaging. The ability to use visible light at lower intensities will also allow us to directly measure the amount of photopigment in the eye, and how the quantity of photopigment changes with bleaching and regeneration. Finally, by using the high quality images to dynamically guide a retinal tracking algorithm, we will probe local retinal sensitivity over abnormal regions of the eye using a dual image stabilization technique and probing retinal sensitivity on a purely local basis. We will use the above techniques to ask a specific series of questions. These questions focus on the control of retinal light absorption, and the effects of aging and disease on the ability of the photoreceptors to collect light. The first question addresses how photoreceptor packing interacts with the amount of photopigment in the outer segments to set the relative absorptivity of cones. If cones actively control their quantum catch, then individuals with larger cones in a given area could be expected to have lower optical density of their pigment. Similarly as the eye ages, there should be adjustments in the photopigments that reflect losses in photoreceptor numbers. In the second set of experiments we will extend this analysis to patients with early age related maculopathy and early geographic atrophy testing the nature and extent of photoreceptor changes. In a final set of experiments we will pursue preliminary data showing that cones have a common phenotypic appearance across a number of early stage diseases. We will test the hypothesis that cones that are diseased, but not yet dead, have a common functional and structural appearance. If true, it would imply that this change could be an effective biomarker of a retina at risk for vision loss and for treatment efficacy.