Advanced Technology to Study Visual Function on a Cellular Scale

在细胞尺度上研究视觉功能的先进技术

• 批准号: 10455547
• 负责人: JACQUE LYNNE DUNCAN
• 金额: $ 103.29万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455547
• 关键词: Affect; Alabama; Animal Model; Animal Testing; Biomedical Engineering; Brain imaging; Cells; Clinic; Clinical; Color; Color Visions; Cone; Development; Disease; Early Diagnosis; Engineering; Environment; Eye; Eye diseases; Funding; Grant; Human; Image; Individual; Investigation; Light; Macaca; Measurement; Measures; Metadata; Methods; Microscopic; Modality; Modeling; Morphology; Motion; Neurophysiology - biologic function; Optical Instrument; Pathway interactions; Patients; Perception; Photic Stimulation; Photoreceptors; Physiological; Physiology; Population; Progress Reports; Property; Psychophysics; Research; Resolution; Retina; Retinal Cone; Retinal Diseases; Retinitis Pigmentosa; Rod; San Francisco; Series; Shapes; Signal Transduction; Software Tools; Specific qualifier value; Specificity; Speed; Stimulus; Structure; System; Technology; Testing; Time; Translating; Translations; Validation; Vision; Vision Tests; Visual; Visual Cortex; Visual Perception; Visual system structure; Visualization; Work; adaptive optics; adaptive optics scanning laser ophthalmoscopy; base; cellular development; clinical application; clinical investigation; clinical translation; computerized tools; cone-rod degeneration; experience; experimental study; fovea centralis; improved; in vivo; innovation; insight; instrument; knowledge translation; microstimulation; nanoscale; new technology; nonhuman primate; optical imaging; optical switch; receptive field; relating to nervous system; response; retinal imaging; retinal rods; sensory input; spatial vision; spatiotemporal; tool; two-photon; vision science; visual control; visual learning; visual performance; visual processing; visual tracking

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.

项目概要 我们请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，中央凹。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 检眼镜 (AOSLO) 系统和准确、高速的眼动跟踪。自适应光学技术 纠正眼睛的缺陷，可用于生成活体视网膜的微观视图 将超清晰的图像传送到视网膜。眼动追踪用于测量和补偿始终存在的眼睛 运动。总之，这些可以实现可视化、跟踪和将光传输到小至视网膜的特征 单视锥光感受器，能够测量空间和色觉的特性 规模空前。尽管这三个系统是相同的，但每个系统的研究范围将是不同的 非常不同。阿拉巴马州的 AOSLO 将用于测试非人类灵长类动物的视力， 伯克利分校将用于对健康人眼进行先进的视力测试，而位于圣保罗的 AOSLO 将用于对健康人眼进行先进的视力测试。 弗朗西斯科将用于研究患有眼病的患者。让 BRP 管理三个方面的主要优势 相同的系统在于它将促进硬件创新以及知识和知识的快速翻译 从动物模型到临床的创新测试。简而言之，具体目标是： 目标 1：针对色觉的高级 AOSLO 显示功能：我们提出了一系列技术方案 进展将扩大 AOSLO 实验的范围，不仅是色觉，还包括空间视觉 和临床应用。具体来说，我们将 (i) 添加 2 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) 集成分光显示器以实现以下实验： 区分视网膜和皮质视觉处理 (iv) 开发 I-TRACK（针对视网膜的改进软件工具） (v) 隐形成像和跟踪。这些工具将支持一系列实验 了解视觉系统如何从其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：为此，我们将 (i) 开发 用于模拟光锥相互作用的先进波前传播工具 (ii) 集成 AOSLO 微刺激 具有用于非人类灵长类动物的 2 光子功能性脑成像系统。我们的目标是使用这些工具 极大地增强了我们对中央凹及其附近感受野的理解。 目标 3：临床转化：我们将把新技术集成到 UCSF 的系统中，以 (i) 研究棒 视杆锥体变性患者的视力 (ii) 测量视杆细胞锥体变性的时间过程、结构和功能 反光视锥细胞 (iii) 研究影响疾病的首选视网膜位点的结构和功能 中央凹和（iv）评估眼部疾病中的内部视网膜功能。