Restoration of visual function by transplantation of optogenetically engineered photoreceptors
Restoration of visual function by transplantation of optogenetically engineered photoreceptors
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DOI：
10.1038/s41467-019-12330-2
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发表时间：
2019-10-04
影响因子：
16.6
通讯作者：
Duebel, Jens
中科院分区：
文献类型：
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作者：
Garita-Hernandez, Marcela;Lampic, Marusa;Duebel, Jens
移植替代光感受器治疗视网膜退行性疾病的一个主要挑战是难以诱导移植细胞生长和维持宿主视网膜的光敏外节段，这取决于与底层视网膜色素上皮（RPE）的适当相互作用。在这里，为了一种不依赖于rpe的治疗方法，我们将一种超极化微生物视蛋白引入新生小鼠的光感受器前体，并将其移植到缺乏光感受器层的失明小鼠中。这些光遗传转化的光感受器是光响应的，它们的移植导致视觉功能的恢复，正如神经节细胞记录和行为测试所显示的那样。随后，我们从人类诱导的多能干细胞中产生锥体光感受器，表达氯泵Jaws。移植到失明小鼠体内后，我们观察到光感受器和神经节细胞水平上的光驱动反应。这些结果表明，将干细胞治疗和光遗传学相结合，视网膜结构和功能修复是可能的。
A major challenge in the treatment of retinal degenerative diseases, with the transplantation of replacement photoreceptors, is the difficulty in inducing the grafted cells to grow and maintain light sensitive outer segments in the host retina, which depends on proper interaction with the underlying retinal pigment epithelium (RPE). Here, for an RPE-independent treatment approach, we introduce a hyperpolarizing microbial opsin into photoreceptor precursors from newborn mice, and transplant them into blind mice lacking the photoreceptor layer. These optogenetically-transformed photoreceptors are light responsive and their transplantation leads to the recovery of visual function, as shown by ganglion cell recordings and behavioral tests. Subsequently, we generate cone photoreceptors from human induced pluripotent stem cells, expressing the chloride pump Jaws. After transplantation into blind mice, we observe light-driven responses at the photoreceptor and ganglion cell levels. These results demonstrate that structural and functional retinal repair is possible by combining stem cell therapy and optogenetics.