Physiological and perceptual examination of vision restoration

视力恢复的生理和知觉检查

• 批准号: 10357890
• 负责人: William H Merigan
• 金额: $ 70.57万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10357890
• 关键词: Address; Animal Model; Behavior; Blindness; Canis familiaris; Cells; Contrast Sensitivity; Discrimination; Disease; Frequencies; Future; Goals; Grant; Human; Image; Individual; Intervention; Learning; Location; Macaca; Measures; Mediating; Methods; Monkeys; Motion; Mus; Neurons; Perception; Perceptual learning; Photophobia; Physiological; Physiology; Primates; Psychophysics; Research; Resolution; Retina; Retinal Diseases; Retinal Ganglion Cells; Series; Shapes; Signal Transduction; Speed; Stimulus; Structure; Testing; Time; Vision; Visual; Visual Perception; Work; adaptive optics; blind; experience; ganglion cell; improved; in vivo; in vivo imaging; nonhuman primate; optical imaging; optogenetics; response; restoration; retinal neuron; sample fixation; sight restoration; visual performance

Project summary Despite the current enthusiasm for optogenetic vision restoration, there is remarkably little direct evidence about whether it can reverse blindness in humans. The feasibility of optogenetics was first suggested by studies from many labs that showed restoration of neuronal visual responses and visually guided behaviors in previously blind mice or dogs. These studies have been very informative in exploring interventions to treat retinal diseases genetically identical to some human disorders. However, they have not addressed restoration in an animal model that closely matches human vision, nor have they examined the perceptual quality of the restored vision. In the studies proposed here, we will address these two issues, first by using macaque monkeys in all studies, the animal model that most resembles humans in visual structure and function, and second by examining the range of visual perceptual abilities made possible by optogenetics. We will use a recently developed in-vivo physiology method to study vision restoration at the level of individual retinal cells in macaque monkeys. This approach will be used in the first aim to examine at a cellular level the spatial, temporal and sensitivity responses of macaque retinal neurons produced by optogenetic restoration. In the second aim we will use controlled fixation psychophysical testing of macaques to examine the range of visual capabilities provided by channelrhodopsin restoration, something that has never been studied. Finally, we will examine the duration of optogenetic restoration, measuring any long-term decrease in function or practice-related improvement in visual function.

项目概要 尽管目前人们对光遗传学视力恢复充满热情，但 关于它是否可以逆转失明的直接证据非常少 人类。许多研究首次提出了光遗传学的可行性 实验室显示神经元视觉反应和视觉引导的恢复 先前失明的老鼠或狗的行为。这些研究非常 为探索治疗遗传相同的视网膜疾病的干预措施提供信息 某些人类疾病。然而，他们还没有解决恢复问题 与人类视觉非常匹配的动物模型，他们也没有检查过 恢复视力的感知质量。在这里提出的研究中，我们将 解决这两个问题，首先在所有研究中都使用猕猴， 在视觉结构和功能上最类似于人类的动物模型，以及 其次，通过检查视觉感知能力的范围 光遗传学。我们将使用最近开发的体内生理学方法来 研究猕猴个体视网膜细胞水平的视力恢复 猴子。该方法将用于第一个目标是在细胞水平上进行检查 猕猴视网膜神经元的空间、时间和敏感性反应 通过光遗传学修复产生。在第二个目标中，我们将使用受控的 对猕猴进行注视心理物理测试，以检查视觉范围 视紫红质通道恢复提供的功能，这是前所未有的 被研究过。最后，我们将检查光遗传学恢复的持续时间， 衡量功能的任何长期下降或与实践相关的改善 视觉功能。