Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.
Department of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, OR, 97239, USA.
Nat Commun. 2019 Mar 15;10(1):1221. doi: 10.1038/s41467-019-09124-x.
Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision.
遗传性和年龄相关性视网膜退行性疾病导致视杆和视锥光感受器进行性丧失，导致失明，但下游视网膜神经元得以保留，可作为光遗传学治疗的靶点。然而，光遗传学方法受到低光灵敏度或缓慢动力学的限制，并且缺乏对环境光变化的适应，也未能证明可以恢复物体视觉。我们发现脊椎动物中波视蛋白（MW-opsin）克服了这些限制，并支持在弱光下的视觉。MW-opsin 使原本失明的色素性视网膜炎小鼠能够区分在标准的 LCD 电脑平板电脑上显示的时间和空间光图案，显示出对环境光变化的适应，并且在偶然的室内光下恢复了野外新物体探索。相比之下，视紫红质的灵敏度相似，但光反应较慢，衰退较大，无法通过这些测试。因此，MW-opsin 提供了恢复图案视觉所需的速度、灵敏度和适应性。
Zotero 插件
