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活体灵长类动物中光遗传学恢复视网膜神经节细胞活性。

Optogenetic restoration of retinal ganglion cell activity in the living primate.

机构信息

Center for Visual Science, University of Rochester, 601 Elmwood Ave, Box 319, Rochester, NY, 14642, USA.

Institute of Optics, University of Rochester, Wilmot Building, 275 Hutchison Road, Box 270186, Rochester, NY, 14627-0186, USA.

出版信息

Nat Commun. 2020 Apr 3;11(1):1703. doi: 10.1038/s41467-020-15317-6.

Abstract

Optogenetic therapies for vision restoration aim to confer intrinsic light sensitivity to retinal ganglion cells when photoreceptors have degenerated and light sensitivity has been irreversibly lost. We combine adaptive optics ophthalmoscopy with calcium imaging to optically record optogenetically restored retinal ganglion cell activity in the fovea of the living primate. Recording from the intact eye of a living animal, we compare the patterns of activity evoked by the optogenetic actuator ChrimsonR with natural photoreceptor mediated stimulation in the same retinal ganglion cells. Optogenetic responses are recorded more than one year following administration of the therapy and two weeks after acute loss of photoreceptor input in the living animal. This in vivo imaging approach could be paired with any therapy to minimize the number of primates required to evaluate restored activity on the retinal level, while maximizing translational benefit by using an appropriate pre-clinical model of the human visual system.

摘要

光遗传学疗法旨在为已经退化且光敏感性不可逆转丧失的视网膜神经节细胞赋予内在的光敏感性。我们结合自适应光学眼底镜和钙成像,在活体灵长类动物的中央凹处光学记录经光遗传学恢复的视网膜神经节细胞的活动。我们从活体动物的健康眼睛中进行记录,将光遗传学激活器 ChrimsonR 引起的活动模式与同一视网膜神经节细胞中天然光感受器介导的刺激进行比较。在治疗后一年以上和活体动物中急性丧失光感受器输入后两周记录光遗传学反应。这种体内成像方法可以与任何治疗方法结合使用,以最大限度地减少评估视网膜水平恢复活动所需的灵长类动物数量,同时通过使用适当的人类视觉系统临床前模型来最大限度地提高转化效益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fe3/7125151/ce7e41990377/41467_2020_15317_Fig1_HTML.jpg

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