Optogenetic strategies to restore vision in patients blind from end-stage retinal degenerations aim to render remaining retinal neurons light-sensitive. We present an innovative combination of multi-electrode array recordings together with a complex pattern-generating light source as a toolset to determine the extent to which neural retinal responses to complex light stimuli can be restored following viral delivery of red-shifted channelrhodopsin in the retinally degenerated mouse. Our data indicate that retinal output level spatiotemporal response characteristics achieved by optogenetic gene therapy closely parallel those observed for normal mice but equally reveal important limitations, some of which could be mitigated using bipolar-cell targeted gene-delivery approaches. As clinical trials are commencing, these data provide important new information on the capacity and limitations of channelrhodopsin-based gene therapies. The toolset we established enables comparing optogenetic constructs and stem-cell-based techniques, thereby providing an efficient and sensitive starting point to identify future approaches for vision restoration.

中文翻译：

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光遗传学基因治疗视力恢复的功能特点。


恢复终末期视网膜变性失明患者视力的光遗传学策略旨在使剩余的视网膜神经元对光敏感。我们提出了多电极阵列记录与复杂模式生成光源的创新组合作为工具集，以确定在视网膜中病毒传递红移通道视紫红质后神经视网膜对复杂光刺激的反应可以恢复的程度退化的老鼠。我们的数据表明，通过光遗传学基因治疗实现的视网膜输出水平时空反应特征与正常小鼠观察到的非常相似，但同样揭示了重要的局限性，其中一些可以通过使用双极细胞靶向基因传递方法来缓解。随着临床试验的开始，这些数据提供了有关基于视紫红质的基因疗法的能力和局限性的重要新信息。我们建立的工具集可以比较光遗传学结构和基于干细胞的技术，从而为确定未来的视力恢复方法提供有效且敏感的起点。