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来绕过眼睛光学所施加的分辨率限制，以测量活体人类视网膜的细胞结构和功能。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，我们将进一步发展自适应光学成像技术，以提高我们现有的对眼睛杆状和锥状光感受器成像的能力，目标是在单个受试者会议中对后极的大区域的每个光感受器进行成像。这将通过双波长成像来实现，我们使用近红外光在高对比度下对视锥细胞进行成像，并同时使用获得的低强度可见光图像，通过图像平均来提供更高分辨率的视杆细胞和视锥细胞图像。在较低强度下使用可见光的能力也将使我们能够直接测量眼睛中光色素的数量，以及光色素的数量如何随着漂白和再生而变化。最后，通过使用高质量图像来动态引导视网膜跟踪算法，我们将使用双图像稳定技术和纯局部基础上探测视网膜灵敏度来探测眼睛异常区域的局部视网膜灵敏度。我们将使用上述技巧来提出一系列特定的问题。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层部分的光色素数量相互作用，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量，那么在给定区域具有较大视锥细胞的个体可能具有较低的色素光密度。同样，随着眼睛年龄的增长，光色素的变化也会反映出光感受器数量的减少。在第二组实验中，我们将把这一分析扩展到患有早期黄斑病变和早期地理萎缩的患者，测试光感受器变化的性质和程度。在最后一组实验中，我们将追求初步数据，显示锥体在许多早期疾病中具有共同的表型外观。我们将检验这个假设，即患病但尚未死亡的锥体具有共同的功能和结构外观。如果这是真的，这将意味着这种变化可能是视网膜有视力丧失风险和治疗效果的有效生物标志物。

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.