Inhibition of mTOR signaling by rapamycin protects photoreceptors from degeneration in rd1 mice  

作　　者：Jia-Liang Yang Tong-Dan Zou Fang Yang Zheng-Lin Yang Hou-Bin Zhang 

机构地区：[1]Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine,Sichuan Provincial People’s Hospital,University of Electronic Science and Technology of China,Chengdu,Sichuan 610072,China [2]Institute of Chengdu Biology,Sichuan Translational Medicine Hospital,Chinese Academy of Sciences,Chengdu,Sichuan 610072,China [3]Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026),Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital,Chengdu,Sichuan 610072,China

出　　处：《Zoological Research》2021年第4期482-486,共5页动物学研究（英文）

基　　金：supported by the National Precision Medicine Project(2016YFC0905200)(Z.Y.&H.Z.);National Natural Science Foundation of China(81570882(H.Z.),81770935(H.Z.));Department of Science and Technology of Sichuan Province,China((2020YJ0445)(H.Z.),2020ZYD037(Z.Y));CAMS Innovation Fund for Medical Sciences(2019-I2M-5-032)(Z.Y.)。

摘　　要：Retinitis pigmentosa(RP)is an inherited retinal degenerative disease that begins with defective rod photoreceptor function,followed by impaired cone function,and complete blindness in its late stage.To date,however,there is no effective treatment for RP.By carrying a nonsense mutation in the Pde6b gene,rd1 mice display elevated cGMP in conjunction with higher intracellular Ca2+in their rod photoreceptors,resulting in fast retinal degeneration.Ca2+has been linked to activation of the mammalian target of rapamycin(mTOR)pathway.The mTOR pathway integrates extracellular and intracellular signals to sense the supply of nutrients and plays a central role in regulating protein and lipid synthesis as well as apoptosis and autophagy.In the present study,we showed that mTOR and phosphorylated mTOR(p-mTOR,activated form of mTOR)are up-regulated in rd1 photoreceptors at postnatal day 10(P10),a pre-degenerative stage.Moreover,the downstream effectors of mTOR,such as pS6K and S6K,are also increased,suggesting activation of the mTOR signaling pathway.Intravitreal administration of rapamycin,a negative regulator of mTOR,inhibits the mTOR pathway in rd1 photoreceptors.Consequently,the progression of retinal degeneration is slower and retinal function is enhanced,possibly mediated by activation of autophagy in the photoreceptors.Taken together,these results highlight rapamycin as a potential therapeutic avenue for retinal degeneration.

关 键 词：DEGENERATION RAPAMYCIN IMPAIRED 

分 类 号：R965[医药卫生—药理学]