视网膜神经元变性损伤所致的视网膜变性性疾病是目前主要的致盲眼病之一，视网膜神经元保护仍然是目前世界范围内的研究难点和热点。最近文献数据提示TREK-TRAAK K2p通道蛋白具有潜在的参与视网膜神经元保护的先决条件并可能参与其调控作用。我们先期研究已证实TRAAK、TREK-1在rds小鼠视网膜的时空表达与感光细胞凋亡存在关联。本课题以体外培养的661W细胞和rds变性小鼠为对象，以膜片钳、confocal等方法，检测全细胞膜电位、K2p通道离子电流及凋亡相关容积等细胞稳态的变化以及凋亡信号传递链上位于该变化下游的Cyt C、线粒体膜电位、Ca2+、caspases等凋亡信号的改变；探讨K2p对视网膜神经元保护的作用和机制；找寻参与视网膜神经元保护的关键性K2p及其时空分布规律。为确立K2p作为防治视网膜变性性疾病的新靶点提供更充分的科学依据。

Retinal degenerative diseases due to degeneration and damage of retinal neurons are among the major blinding diseases currently. Neuronal protection is still the hotspot of research worldwide.It has indicated recently that TREK-TRAAK K2p channal protein had the potential of protecting retinal neuron and might play a role in the regulation of neuronal protection.Our preliminary study has identified the expression of TRAAK、TREK-1 in rds mice correlated with apoptosis of photoreceptors either spatially or temporally. We will use 661W cells cultured in vitro and rds mice as our object, detecting the changes of cell homeostasis including total cell membrane potential, K2p channel ionic current and apoptotic volume as well as the changes of signals of apoptosis which are downstream located such as CytC, mitochodrial membrane ,Ca2+ and caspases by patch clamp, confocal and other methods. We will explore the role and mechanism of K2p in neuronal protection, and look for the key K2p and its spatial and temporal expression, so that we could provide more evidents for establishing K2p as a new target for prevention and treatment of retinal degenerative diseases.