Physiological and perceptual examination of vision restoration

项目摘要 尽管目前对光遗传视力恢复的热情， 很少有直接证据表明它是否能逆转失明， 人类光遗传学的可行性首先是由许多研究提出的 实验室显示神经元视觉反应的恢复， 在先前失明的小鼠或狗中的行为。这些研究非常 在探索治疗遗传上相同的视网膜疾病的干预措施方面提供了信息 一些人类疾病然而，他们没有在一个 与人类视觉密切匹配的动物模型，他们也没有检查 恢复视觉的感知质量。在本研究中，我们将 解决这两个问题，首先在所有研究中使用猕猴， 在视觉结构和功能上与人类最相似的动物模型，以及 第二，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， 研究猕猴视网膜细胞个体水平的视力恢复 猴子这种方法将用于第一个目的，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 由光遗传学修复产生。在第二个目标中，我们将使用受控 猕猴的注视心理物理测试，以检查视觉范围 通道视紫红质恢复提供的能力，这是从来没有 本文研究了最后，我们将检查光遗传学恢复的持续时间， 测量功能或实践相关改善的任何长期下降， 视觉功能

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.