Physiological and perceptual examination of vision restoration

视力恢复的生理和知觉检查

• 批准号: 10576819
• 负责人: William H Merigan
• 金额: $ 70.73万
• 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 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576819
• 关键词: 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; redshift; 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.

项目总结 尽管目前人们对光遗传视力恢复充满热情，但仍有 令人惊讶的是，几乎没有直接证据表明它能否扭转失明 人类。光遗传学的可行性最早是由许多研究提出的。 显示神经元视觉反应和视觉指导恢复的实验室 先前失明的小鼠或狗的行为。这些研究已经非常 在探索治疗基因相同的视网膜疾病的干预措施方面提供信息 人类的某些疾病。然而，他们并没有在一个 与人类视觉非常接近的动物模型，他们也没有检查 恢复的视力的知觉质量。在这里提出的研究中，我们将 解决这两个问题，首先在所有研究中使用猕猴， 在视觉结构和功能上最接近人类的动物模型，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来 从单个视网膜细胞水平研究猕猴的视力恢复 猴子。这种方法将被用于第一个目标，以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 由光遗传修复产生。在第二个目标中，我们将使用受控 猕猴注视心理物理学检查视力范围的实验研究 通道视紫质修复提供的能力，这是从未有过的 已经研究过了。最后，我们将研究光遗传恢复的持续时间， 衡量任何长期的功能下降或与实践相关的改善 视觉功能。

项目成果

Restoring vision at the fovea.

恢复中央凹的视力。

• DOI: 10.1016/j.cobeha.2019.10.003
• 发表时间: 2019-12
• 期刊: Current opinion in behavioral sciences
• 影响因子: 5
• 作者: McGregor JE

Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates.

抗体中和构成玻璃体内腺相关病毒载体基因递送至非人类灵长类动物的障碍。

• DOI: 10.1038/gt.2014.115
• 发表时间: 2015-02
• 期刊: GENE THERAPY
• 影响因子: 5.1
• 作者: Kotterman, M. A.;Yin, L.;Strazzeri, J. M.;Flannery, J. G.;Merigan, W. H.;Schaffer, D. V.
• 通讯作者: Schaffer, D. V.