光遗传学技术及其在视网膜变性性疾病治疗中的应用

The application of optogeneUcs in the treatment of retinal degeneration disease

光遗传学技术是一种将光学和遗传学技术相结合的新兴技术。其主要原理是应用遗传学方法将特异的视蛋白导入目标神经元，再用相应波长或频率的光刺激视蛋白，使神经元兴奋或抑制，进而控制特定神经环路的活动，最终起到调控实验动物生理活动和行为的作用。在视网膜色素变性、老年性黄斑变性等视网膜变性性疾病中，应用光遗传学技术玻璃体腔或视网膜下注射视蛋白基因，由外界给予相应的光照激活视蛋白，模拟并代替视网膜光感受器功能，可在一定程度上恢复患者视力。但其存在病毒转染有潜在风险、目标细胞的准确选择难以把握、治疗后视力分辨率能否恢复正常尚不确定等局限性。随着光敏感度更高、更易被激发的新型视蛋白和具有更高转染效率的病毒载体不断研发，相信光遗传学技术将会应用在更多眼科领域。

Optogenetics is a novel technique which combines optics with genetics, using genetic means, a selected opsin protein is ectopically expressed in target neurons, which are then stimulated by light to moderate the neuronal circuit, as a consequence to regulate the animal＇s behaviors. Retinal degeneration like retinitis pigmentosa and aged macular degeneration causes visual impairment and eventual blindness. Optogeneties techniques have opened the door to creating artificial photoreceptors in the remaining retinal circuits of retinal degeneration retinas via gene therapy. However, there are still limitations in optogenetics technique, for example, potential risk in virus infection, the choice of target cells and the low visual resolution of the experiment animal. It has been reported that vision was successfully restored to a certain extent in animal model using optogenetics technique. With higher photosensitivity of opsin protein, longer activation kinetics and higher transfection efficiency of virus vector, optogenetics techniquesr application in ophthalmology will be improved.