Overexpression of parkin protects retinal ganglion cells in experimental glaucoma.
Overexpression of parkin protects retinal ganglion cells in experimental glaucoma.
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Parkin 过度表达可保护实验性青光眼中的视网膜神经节细胞
DOI：
10.1038/s41419-017-0146-9
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发表时间：
2018-01-24
影响因子：
9
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Dai Y;Hu X;Sun X
青光眼是不可逆性失明的主要原因，其特征是视网膜神经节细胞（RGCs）的进行性损伤。越来越多的证据表明，线粒体自噬受损与神经退行性疾病有关，而E3泛素连接酶可能起关键作用。然而，帕金森氏病与青光眼之间的病理生理关系在很大程度上仍不清楚。用经角膜激光光凝诱导的慢性高血压性青光眼大鼠，我们发现高血压视网膜中帕金及其下游视神经蛋白的蛋白水平升高。高血压视神经LC3-II / LC3-I比值、线粒体自噬体数量、不健康线粒体数量增加。通过病毒载体过度表达parkin可提高青光眼大鼠体内和体外兴奋毒性下RGC的存活率。它还促进了优神经蛋白的表达，改善了线粒体的健康。在帕金森过表达的青光眼大鼠中，视神经中LC3-II与LC3-I之比、LAMP1水平和丝粒体数量在眼内压（IOP）升高后第3天下降，但在第2周升高。说明青光眼大鼠RGCs中存在线粒体自噬功能障碍。过度表达parkin对RGCs具有显著的保护作用，并在一定程度上恢复了累积IOP升高后的线粒体自噬功能障碍。
Glaucoma is a leading cause of irreversible blindness and characterized by progressive damage of retinal ganglion cells (RGCs). Growing evidences have linked impaired mitophagy with neurodegenerative diseases, while the E3 ubiquitin ligase parkin may play a key role. However, the pathophysiological relationship between parkin and glaucoma remains largely unknown. Using chronic hypertensive glaucoma rats induced by translimbal laser photocoagulation, we show here that the protein level of parkin and its downstream optineurin proteins were increased in hypertensive retinas. The ratio of LC3-II to LC3-I, the number of mitophagosomes, and unhealthy mitochondria were increased in hypertensive optic nerves. Overexpression of parkin by viral vectors increased RGC survival in glaucomatous rats in vivo and under excitotoxicity in vitro. It also promoted optineurin expression and improved mitochondrial health. In parkin-overexpressed glaucomatous rats, the ratio of LC3-II to LC3-I, LAMP1 level, and the number of mitophagosomes in optic nerve were decreased at 3 days, yet increased at 2 weeks following intraocular pressure (IOP) elevation. These findings demonstrate that dysfunction of mitophagy exist in RGCs of glaucomatous rats. Overexpression of parkin exerted a significant protective effect on RGCs and partially restored dysfunction of mitophagy in response to cumulative IOP elevation.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
9
作者：
通讯作者：
--
影响因子：
3.5
作者：
Gegg, Matthew E.;Cooper, J. Mark;Taanman, Jan-Willem
通讯作者：
Taanman, Jan-Willem
高压诱导视网膜神经节细胞 mtDNA 改变和随后的细胞凋亡
影响因子：
5.3
作者：
Zhang SH;Gao FJ;Sun ZM;Xu P;Chen JY;Sun XH;Wu JH
通讯作者：
Wu JH
影响因子：
--
作者：
Pascucci B;D'Errico M;Romagnoli A;De Nuccio C;Savino M;Pietraforte D;Lanzafame M;Calcagnile AS;Fortini P;Baccarini S;Orioli D;Degan P;Visentin S;Stefanini M;Isidoro C;Fimia GM;Dogliotti E
通讯作者：
Dogliotti E