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: 10250413
• 负责人: JACQUE LYNNE DUNCAN
• 金额: $ 102.59万
• 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/10250413
• 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.

项目摘要 我们要求支持继续开发和增强三种最先进的光学仪器， 将被用来回答有关视网膜中最重要和最具挑战性的区域的问题 书房，中心凹。这些仪器建立在两个关键技术优势上--自适应光学扫描激光 眼底镜(AOSLO)系统和准确、高速的眼动跟踪。自适应光学技术 纠正眼睛中的缺陷，并可用于生成活视网膜的显微图像和 将超清晰的图像传送到视网膜。眼睛跟踪被用来测量和补偿一直存在的眼睛 动议。这些功能结合在一起，允许可视化、跟踪和将光传递到视网膜功能，小到 单锥体感光器，使测量空间和颜色视觉特性成为可能 规模史无前例。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。阿拉巴马州的AOSLO将用于测试非人类灵长类动物的视力，AOSLO将在 伯克利分校将用于对健康的人眼进行高级视力测试，旧金山的AOSLO将用于 弗朗西斯科将被用于研究眼病患者。让BRP管理三个方面的主要优势 相同的系统将促进硬件创新以及知识和 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：高级AOSLO彩色视觉显示能力：我们提出了一系列技术 发展将扩大AOSLO实验的范围，不仅是颜色视觉，也包括空间视觉 和临床应用。具体地说，我们将(I)添加双光子刺激(Ii)开发新的显示方法 固定在世界坐标中的大刺激(III)集成双分裂显示器以使实验能够 区分视网膜和皮质视觉处理(IV)开发I-Track(改进的视网膜软件工具- 应急视力测试)和(V)隐形成像和跟踪。这些工具将使一系列实验成为可能 学习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：增强的AOSLO系统和空间视觉建模：在这个目标中，我们将(I)开发 模拟光锥相互作用的先进波前传播工具(II)集成AOSLO微刺激 在非人类灵长类动物中使用双光子脑功能成像系统。我们的目标是使用这些工具 极大地增强了我们对中心凹及其附近的接受区的理解。 目标3：临床翻译：我们将在加州大学旧金山分校将新技术集成到系统中，以(I)研究杆 视杆-视锥细胞退行性变患者的视力(II)测量时间进程、结构和功能 视锥反射障碍(III)研究影响视网膜功能的疾病的首选视网膜部位的结构和功能 黄斑中心凹和(Iv)评估眼病患者的视网膜内部功能。