小鼠复明：发现光开关分子

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小鼠复明：发现光开关分子
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来自the Universities of Bern in Switzerland and Göttingen in Germany 的研究者在PLOS Biology发表Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool。他们成功地使失明的小鼠复明。他们建立了一个分子光开关，这可能用于未来的治疗。* m  {' r+ _4 r$ r- |
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在世界上成千上万的人患有遗传性的失明症，这些病人眼中的感光细胞会逐渐消失（退行性疾病）。虽然视网膜上的感光细胞丢失，但是视网膜深处的非感光细胞没有受到损失。于是研究者将一种新的感光蛋白注入到这些幸存的视网膜细胞中将它们转变为替代感光器。
5 m8 H" i+ n2 ]1 t; K0 Z# N) v" v! q- H文章的通讯作者Sonja Kleinlogel说“：开始时的问题是我们是否可以设计光激活蛋白激活特定细胞中的信号通路？，换句话说，是否可以可以通过光刺激激活特定细胞中的天然感光信号通路，而不是依赖于生理条件下的神经调控？”, F- e/ [4 I2 X9 |1 V! x+ }
研究者修饰的细胞原本接受来自感光细胞的化学信号，修饰后这些细胞直接接受光信号，整合了原本感光细胞的功能，形成替代性感光细胞。给这些细胞安装上感光天线使得视网膜的信号收集功能被最大限度的利用了起来。本文的共同作者Siegrid Löwel 和Justyna Pielecka-Fortuna（neuroscientists at the University of Göttingen）说：“使用视觉成像技术检测实验小鼠的神经活性，我们发现替代性的感光器能够激活visual cortex（ the part of the cortex that analyzes visual signals）”。2 b4 D$ B* z, ?0 A' q# X
结果显示：实验鼠可以在日光下视物，对光刺激做出反应以及学习视觉出发的动作。
( z2 P" M# m2 |# Z# QSonja Kleinlogel表示：”这一新的治疗方案可能可以恢复退行性失明病人的视觉。”这一方案的优点是可以恢复病人在日光下的视觉，不需要light intensifiers or image converter goggles。同时她也表示：“但是，这需要2-3年的时间验证这一方案在临床上的效果，”3 u% s1 [1 P% i- Q' @6 V* w
另外，这一新的治疗措施展现了其他一些疾病治疗的其他可能性方案，比如pain, depression and epilepsy.
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Vision restored to blind mice: Molecular 'light switch' found4 I3 z8 g+ z5 d- {/ ~% l6 p
Date:9 Z; {7 q! E5 W, D! ]$ P4 t
May 7, 2015# a. P1 I. o) ?# _' N( N$ M7 D
Source:
" a- v! S) D7 k4 TUniversity of Bern) Q. X/ Y1 B+ e, b' q6 h
Summary:
  |* J1 x, a7 l- cScientists have succeeded in restoring vision to blind mice. They've developed a molecular light switch as a potential therapy for acquired blindness.. s2 E6 ?9 p+ w6 B
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Scientists from the Universities of Bern in Switzerland and Göttingen in Germany have succeeded in restoring vision to blind mice. They've developed a molecular light switch as a potential therapy for acquired blindness.
7 w& P& G6 o; R3 {: [3 {, B# zHereditary blindness caused by a progressive degeneration of the light-sensing cells in the eye, the photoreceptors, affects millions of people worldwide. Although the light-sensing cells are lost, cells in deeper layers of the retina, which normally cannot sense light, remain intact. Scientists from Bethe Universities of Bern, Switzerland, and Göttingen, Germany, now introduced a new light-sensing protein into the surviving retina cells, thus turning them into "replacement photoreceptors." The results were published in PLoS Biology." {. l0 l1 R( G# J9 b
"The question was: Can we design light-activatable proteins that gate specific signaling pathways in specific cells?," Sonja Kleinlogel, corresponding author of the paper whose research group is based at the University of Bern, says. "In other words, can the natural signaling pathways of the target cells be retained and just modified in a way to be turned on by light instead of a neurotransmitter released from a preceding neuron?"4 l% e( l' w6 ~! s: g: x- J; x
The scientists molecularly modified the cells that normally would have received direct information from the photoreceptors in a way that they reacted to light stimuli instead of chemical signals, thus turning them into replacement photoreceptors. Integrating a new "light antenna" into the surviving cells has the advantage that signal computation of the retina is maximally utilized. "Using optical imaging of neuronal activity in the treated mice, we showed that these replacement photoreceptors were able to activate the visual cortex -- the part of the cortex that analyzes visual signals -- more strongly again," co-authors Siegrid Löwel and Justyna Pielecka-Fortuna, neuroscientists at the University of Göttingen, say.
8 I# E* e( |3 X/ A9 E+ WThe result: The mice were able to see under daylight conditions, react to visual stimuli and learn visually triggered behaviors. "The new therapy can potentially restore sight in patients suffering from any kind of photoreceptor degeneration," Sonja Kleinlogel explains. According to her, the major improvement of the new approach is that patients should be able to see under normal daylight conditions without the need for light intensifiers or image converter goggles. "However, it will take at least another two or three years before the new light antenna can be tested in the clinical setting," she adds. Furthermore, the novel principle opens a whole palette of new possibilities to potentially treat conditions such as pain, depression and epilepsy.
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The above story is based on materials provided by University of Bern. Note: Materials may be edited for content and length.4 F* E1 N# `. w# d
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, P0 s  U$ k- T; \Journal Reference:5 f8 l9 s- R! j  |6 V5 A
        1        Michiel van Wyk, Justyna Pielecka-Fortuna, Siegrid Löwel, Sonja Kleinlogel. Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool. PLOS Biology, 2015; 13 (5): e1002143 DOI: 10.1371/journal.pbio.1002143