图片说明:眼部插入特殊蛋白能使失明小鼠恢复对光线的感觉。
(图片来源:Punchstock)
瑞士、美国及加拿大科学家近日研究发现,将一种来自藻类的光敏蛋白插入到失明小鼠的眼部细胞后,使得它们成功地恢复了对光线的感觉。研究人员希望,类似的方法将来可以用于治疗特定种类的人类失明。相关论文4月27日在线发表于《自然—神经学》(Nature Neuroscience)上。
这种光敏蛋白名为channelrhodopsin-2(ChR2),藻类用它来进行光合作用。一些科学家对于用它来替换动物眼部受损或缺失的光感受器极为感兴趣。在患老年黄斑变性(AMD)的人眼部,这种光感受器的损伤尤为常见,但是一直没有合适的治疗方法。
在最新的研究中,瑞士Friedrich Miescher生物医学研究所(FMI)的Botond Roska和研究小组关注的是眼部完全丧失光感受器的小鼠。这些光感受器通常负责在视觉图像形成之前将光输送到双极细胞(bipolar cells)。
研究人员使用一种无害病毒搭载ChR2进入到小鼠的双极细胞。虽然以这种方式进入的双极细胞量只占总量的7%,但已足够光信号传输到视网膜的下一层——神经节细胞(ganglion cells),直至最终到达大脑。结果发现,当照射灯光时,与普通小鼠对光线完全无反应相比,黑暗中的实验小鼠跳跃起来,表明它们感受到了光线。
研究人员随后对这些小鼠的视觉进行了测试,结果表明实验小鼠要胜过普通小鼠。但是实验小鼠的视觉恢复程度到底如何不得而知。Roska说:“毕竟,你又没法问它们。”
目前,Roska及同事已经和一些临床小组建立了合作关系,以在人类身上研发这项技术。不过Roska表示,即使这样,它也很可能是最后的可供选择的临床方案。他说,如果哪怕还有一点点的视觉残留,采用其它治疗方法可能更为有效,“这一方法应该只适用于完全失去视觉的时候。”(科学网 梅进/编译)
(Nature Neuroscience),doi:10.1038/nn.2117,Pamela S Lagali,Botond Roska
生物谷推荐原始出处:
Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration
Pamela S Lagali1,4, David Balya1,4, Gautam B Awatramani1,3,4, Thomas A Münch1, Douglas S Kim2, Volker Busskamp1, Constance L Cepko2 & Botond Roska1
Abstract
Genetically encoded optical neuromodulators create an opportunity for circuit-specific intervention in neurological diseases. One of the diseases most amenable to this approach is retinal degeneration, where the loss of photoreceptors leads to complete blindness. To restore photosensitivity, we genetically targeted a light-activated cation channel, channelrhodopsin-2, to second-order neurons, ON bipolar cells, of degenerated retinas in vivo in the Pde6brd1 (also known as rd1) mouse model. In the absence of 'classical' photoreceptors, we found that ON bipolar cells that were engineered to be photosensitive induced light-evoked spiking activity in ganglion cells. The rescue of light sensitivity was selective to the ON circuits that would naturally respond to increases in brightness. Despite degeneration of the outer retina, our intervention restored transient responses and center-surround organization of ganglion cells. The resulting signals were relayed to the visual cortex and were sufficient for the animals to successfully perform optomotor behavioral tasks.