Centre for Nanotechnology & Regenerative Medicine, UCL Division of Surgery & Interventional Science, University College London, London, UK.
N Biotechnol. 2013 Jun 25;30(5):461-74. doi: 10.1016/j.nbt.2013.04.007. Epub 2013 May 7.
The advent of optogenetics provides a new direction for the field of neuroscience and biotechnology, serving both as a refined investigative tool and as potential cure for many medical conditions via genetic manipulation. Although still in its infancy, recent advances in optogenetics has made it possible to remotely manipulate in vivo cellular functions using light. Coined Nature Methods' 'Method of the Year' in 2010, the optogenetic toolbox has the potential to control cell, tissue and even animal behaviour. This optogenetic toolbox consists of light-sensitive proteins that are able to modulate membrane potential in response to light. Channelrhodopsins (ChR) are light-gated microbial ion channels, which were first described in green algae. ChR2 (a subset of ChR) is a seven transmembrane α helix protein, which evokes membrane depolarization and mediates an action potential upon photostimulation with blue (470 nm) light. By contrast to other seven-transmembrane proteins that require second messengers to open ion channels, ChR2 form ion channels themselves, allowing ultrafast depolarization (within 50 milliseconds of illumination). It has been shown that integration of ChR2 into various tissues of mice can activate neural circuits, control heart muscle contractions, and even restore breathing after spinal cord injury. More compellingly, a plethora of evidence has indicated that artificial expression of ChR2 in retinal ganglion cells can reinstate visual perception in mice with retinal degeneration.
光遗传学的出现为神经科学和生物技术领域提供了新的方向,它既是一种精细的研究工具,也可以通过基因操作为许多医学病症提供潜在的治疗方法。尽管它仍处于起步阶段,但光遗传学的最新进展已经使得使用光远程操纵体内细胞功能成为可能。该技术被评为 2010 年《自然方法》的“年度方法”,光遗传学工具具有控制细胞、组织甚至动物行为的潜力。这个光遗传学工具包由能够响应光调制膜电位的光敏感蛋白组成。通道视紫红质(ChR)是光门控微生物离子通道,最初在绿藻中被描述。ChR2(ChR 的一个子集)是一种跨膜七螺旋α螺旋蛋白,在蓝光(470nm)光刺激下会引起膜去极化并介导动作电位。与其他需要第二信使打开离子通道的跨膜七蛋白不同,ChR2 本身形成离子通道,允许超快速去极化(在光照 50 毫秒内)。已经表明,将 ChR2 整合到小鼠的各种组织中可以激活神经回路、控制心肌收缩,甚至在脊髓损伤后恢复呼吸。更有说服力的是,大量证据表明,在视网膜神经节细胞中人工表达 ChR2 可以恢复视网膜变性小鼠的视觉感知。