原发性视网膜色素变性是目前导致不可逆性盲的一类重要眼底病,由基因突变编码异常蛋白引发的内质网应激与氧化应激损伤在发病机制中发挥重要作用。我们前期研究发现在多种外源性损伤中,通过抑制mTOR信号使神经元细胞休眠,可以有效地减轻细胞内质网应激与氧化应激损伤,并表现出良好的神经保护作用。因此我们提出学术假说:通过抑制mTOR信号可以使视网膜神经元进入低能量代谢,低蛋白合成,稳定存活的休眠状态,有效抑制了细胞内质网应激与氧化应激损伤,阻断了由内源性基因突变引发的程序化死亡。本课题拟构建原发性视网膜色素变性患者源性小型多能干细胞(IPS)库,并将携带不同致病基因的IPS细胞定向分化为视网膜神经元细胞;通过特异性抑制mTOR信号使细胞休眠，检验对神经元细胞的保护作用;另外应用遗传性视网膜色素变性大鼠体内实验共同验证学术假说。以mTOR为分子靶点的细胞休眠可能成为视网膜退行性疾病具有共性的神经保护机制。

Retinitis pigmentosa (RP) is one of the major reitnal diseases leading to irreversible blindness. The ER stress and oxidative stress induced by overloaded misfolded-protein, which is transcribed from mutant genes, play an important role in the molecular mechanism of retinitis pigmentosa. From our previous studies, we find that during various external insults, cell dormancy via inhibiting mTOR signals remarkably attenuated ER stress and oxidative stress injuries in retinal neurons, which showed excellent neuroprotective effect.Therefore we propose a hypothesis that cell dormancy via mTOR signal inhibition is able to reduce cellular energy metabolism and protein synthesis, which makes cells live in a lower and more stable bioenergy status. Cell dormancy blocks the death cascade of retinal neurons by inhibiting ER stress and oxidative stress. To prove our hypothesis, we will establish a RP patient-derived IPS cell bank, and then IPS cells with mutant genes will be further differentiated into retinal neurons. Next, these RP patient-derived retinal neurons will be used to test the neuroprotective effect of induced-cell dormancy via specifically inhibiting mTOR signals. Moreover, as a typical animal model, the inherited retinitis pigmentosa rats (RCS rats) will be used in this study as well to provide evidence in vivo. The induced-cell dormancy targeting mTOR signals might be a common mechanism to protect retinal neurons in retinitis pigmentosa.