Optical Imaging of the Photoreceptor-RPE Complex

描述(申请人提供)：当光感受器收集光并对光做出反应时，人类视觉开始。正常的光感受器功能及其来自视网膜色素上皮(RPE)的支持对于正常视力是必不可少的，然而在体内评估这些过程的技术是有限的。目前的光学和电生理技术空间分辨率和灵敏度有限，且仅针对特定的功能过程。新的光学模式是快速、特异和非侵入性的，有望极大地扩展我们更准确和完全地监测光感受器RPE复合体的能力。我们将使用自适应光学(AO)和光学相干层析成像(OCT)来获得前所未有的3D分辨率，以在细胞水平上研究光感受器和RPE层的生理机制。AOOCT将与我们开发的一种精密敏感的相位技术相结合，实现进一步的改进。该技术测量的光学长度变化小至45 nm。这比单个锥形外段(OS)盘略厚，比超高分辨率OCT的轴向分辨率高近100倍。其具体目的是：(1)确定控制光感受器中光捕获的物理参数；(2)评估光感受器中的光散射特性；以及(3)评估RPE中的光散射特性。 与公共健康相关：这项研究的长期目标是建立高分辨率的成像方法，在细胞尺度上探测视网膜的结构和功能。这项研究的目标细胞是光感受器和视网膜色素上皮细胞，两者都与光的捕获和视觉的第一步有关。由于疾病始于细胞和分子水平，在单细胞水平和在患者身上研究这些病理破坏的能力有望改进对世界上一些最致盲的疾病的早期发现和治疗监测。

DESCRIPTION (provided by applicant): Human vision starts when photoreceptors collect and respond to light. Normal photoreceptor function and its support from the underlying retinal pigment epithelium (RPE) are essential for normal vision, yet techniques to assess these processes in vivo are limited. Current optical and electrophysiological techniques have limited spatial resolution and sensitivity, and target only specific functional processes. New optical modalities that are rapid, specific, and noninvasive hold the promise of greatly expanding our capability to monitor more accurately and completely the photoreceptor RPE complex. We will use adaptive optics (AO) and optical coherence tomography (OCT) to achieve unprecedented 3D resolution for studying physiological mechanisms at the cellular level in the photoreceptor and RPE layers. Further improvements will be realized using AOOCT in conjunction with an exquisitely sensitive phase technique that we have developed and that measures optical length changes as small as 45nm.This is slightly thicker than a single cone outer segment (OS) disc and nearly 100times better than the axial resolution of ultra high resolution OCT. The specific aims are to: (1) Determine the physical parameters that control light capture in photoreceptors; (2) Evaluate properties of light scatter in photoreceptors; and (3) Evaluate properties of light scatter in RPE. PUBLIC HEALTH RELEVANCE: The long term goal of this research is to establish high-resolution imaging methods that probe structure and function of the retina at the cellular scale. The target cells in this study are photoreceptors and retinal pigment epithelial cells, both associated with the capture of light and the first step in seeing. As disease starts at the cellula and molecular levels, the ability to study these pathological disruptions at the single cell level and in patients promises improvements in early detection and treatment monitoring of some of the most blinding diseases in the world.