Advanced Technology to Study Visual Function on a Cellular Scale

项目摘要 我们正在寻求支持，以继续开发和增强三种最先进的光学仪器， 将用于回答有关视网膜中最重要和最具挑战性的区域的问题， 研究中心凹这些仪器建立在两个关键技术优势之上-自适应光学扫描激光 这是一种先进的眼底镜（AOSLO）系统和精确、高速的眼球运动跟踪技术。自适应光学技术 矫正眼睛的缺陷，并可用于生成活体视网膜的显微镜视图， 将超清晰的图像传送到视网膜。眼动跟踪用于测量和补偿始终存在的眼睛 议案总之，这些允许可视化，跟踪和传递光到视网膜功能，小到 单锥光感受器，使测量的空间和色觉的属性上， 前所未有的规模。虽然这三个系统将是相同的，但每个系统的研究范围将是 非常不同位于亚拉巴马的AOSLO将用于测试非人类灵长类动物的视力， 伯克利将用于对健康人眼进行先进的视力测试，而旧金山的AOSLO将用于对健康人眼进行视力测试。 弗朗西斯科将用于研究眼疾患者。让BRP管理三个方面的主要优势是 相同的系统是，它将促进硬件创新加上知识的快速翻译， 从动物模型到临床的创新测试。简言之，具体目标是： 目标1：先进的AOSLO彩色视觉显示能力：我们提出了一系列技术 这些进展将扩大AOSLO实验的范围，不仅是色觉，还有空间视觉 和临床应用。具体来说，我们将（i）增加双光子刺激（ii）开发新的方法来显示 固定在世界坐标中的大刺激（iii）集成了双视显示器以实现实验， （iv）开发I-TRACK（改进的视网膜视觉处理软件工具， 视情况而定的视力测试）和（v）不可见的成像和跟踪。这些工具将使一系列的实验 学习视觉系统如何从感官输入中提取颜色和空间信息。 目标2：增强AOSLO系统和空间视觉建模：在这个目标中，我们将（i）开发 先进的波前传播工具来模拟光锥相互作用（ii）集成AOSLO微刺激 用一个系统在非人类灵长类动物身上进行双光子脑功能成像。我们的目标是利用这些工具， 极大地增强了我们对中央窝及其附近感受野的了解。 目标3：临床转化：我们将把新技术整合到UCSF的系统中，以（i）研究棒 视杆-视锥变性患者的视力（ii）测量视杆-视锥变性的时间过程、结构和功能。 （iii）研究影响视网膜功能的疾病中优选视网膜位点的结构和功能。 中心凹和（iv）评估眼部疾病中的内部视网膜功能。

Project Summary We are asking for support to continue to develop and enhance three state-of-the-art optical instruments that will be used to answer questions about the most important and the most challenging region in the retina to study, the fovea. The instruments are built upon two key technical strengths - adaptive optics scanning laser ophthalmoscope (AOSLO) systems and accurate, high-speed eye-motion tracking. Adaptive optics technology corrects the imperfections in the eye and can be used to generate microscopic views of the living retina and deliver ultra-sharp images to the retina. Eye tracking is used to measure and compensate for ever-present eye motion. Together, these allow for visualization, tracking and delivery of light to retinal features as small as single cone photoreceptors, enabling measurements of properties of spatial and color vision on an unprecedented scale. Although the three systems will be identical, the scope of study for each system will be very different. The AOSLO at in Alabama will be used to test vision in non-human primates, the AOSLO in Berkeley will be used to perform advanced vision testing on healthy human eyes, and the AOSLO in San Francisco will be used to study patients with eye disease. The key advantage of having the BRP manage three identical systems is that it will facilitate hardware innovations plus rapid translation of knowledge and innovative testing from animal models to the clinic. Briefly, the specific aims are: Aim 1: Advanced AOSLO display capabilities for color vision: We propose a series of technical developments will expand the scope of AOSLO experiments, not just for color vision, but also spatial vision and clinical applications. Specifically, we will (i) add 2-photon stimulation (ii) develop new methods to display large stimuli that are fixed in world-coordinates (iii) integrate dichoptic displays to enable experiments that distinguish retinal from cortical visual processing (iv) develop I-TRACK (improved software tools for retina- contingent vision testing) and (v) invisible imaging and tracking. These tools will enable a series of experiments to learn how the visual system extracts color and spatial information from its sensory inputs. Aim 2: Enhanced AOSLO systems and modeling for spatial vision: In this aim we will (i) develop advanced wavefront propagation tools to model light-cone interactions (ii) integrate AOSLO microstimulation with a system for 2-photon functional brain imaging in non-human primates. We aim to use these tools to greatly enhance our understanding of receptive fields at and near the fovea. Aim 3: Clinical translation: We will integrate the new technology into the system at UCSF to (i) study rod vision in patients with rod-cone degenerations (ii) measure the time course, structure and function of dysflective cones (iii) investigate the structure and function of the preferred retinal locus in diseases that affect the fovea and (iv) assess inner retinal function in eye disease.