Wen Xiangyi, Liao Ping, Luo Yuncheng, Yang Linghui, Yang Huaiyu, Liu Longqian, Jiang Ruotian
Department of Ophthalmology, Department of Optometry and Visual Science, Laboratory of Optometry and Vision Sciences, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Sci Adv. 2022 Sep 9;8(36):eabn8785. doi: 10.1126/sciadv.abn8785. Epub 2022 Sep 7.
Retinal ganglion cells (RGCs) not only collect but also integrate visual signals and send them from the retina to the brain. The mechanisms underlying the RGC integration of synaptic activity within retinal circuits have not been fully explored. Here, we identified a pronounced expression of tandem pore domain acid-sensitive potassium channel 3 (TASK-3), a two-pore domain potassium channel (K2P), in RGCs. By using a specific antagonist and TASK-3 knockout mice, we found that TASK-3 regulates the intrinsic excitability and the light sensitivity of RGCs by sensing neuronal activity-dependent extracellular acidification. In vivo, the blockade or loss of TASK-3 dampened pupillary light reflex, visual acuity, and contrast sensitivity. Furthermore, overexpressing TASK-3 specifically in RGCs using an adeno-associated virus approach restored the visual function of TASK-3 knockout mice and aged mice where the expression and function of TASK-3 were reduced. Thus, our results provide evidence that implicates a critical role of K2P in visual processing in the retina.
视网膜神经节细胞（RGCs）不仅收集视觉信号，还对其进行整合，并将信号从视网膜发送至大脑。视网膜神经节细胞整合视网膜回路内突触活动的机制尚未得到充分探索。在此，我们发现双孔域酸敏感钾通道3（TASK-3，一种双孔域钾通道（K2P））在视网膜神经节细胞中显著表达。通过使用特异性拮抗剂和TASK-3基因敲除小鼠，我们发现TASK-3通过感知神经元活动依赖性细胞外酸化来调节视网膜神经节细胞的内在兴奋性和光敏感性。在体内，TASK-3的阻断或缺失会减弱瞳孔光反射、视力和对比敏感度。此外，使用腺相关病毒方法在视网膜神经节细胞中特异性过表达TASK-3可恢复TASK-3基因敲除小鼠和TASK-3表达及功能降低的老年小鼠的视觉功能。因此，我们的研究结果表明K2P在视网膜视觉处理中起关键作用。
