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Acteoside inhibits autophagic apoptosis of retinal ganglion cells to rescue glaucoma‐induced optic atrophy
Author(s) -
Chen Qianbo,
Xi Xiaoting,
Zeng Yong,
He Zhendan,
Zhao Jianfeng,
Li Yan
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28586
Subject(s) - autophagy , pi3k/akt/mtor pathway , optineurin , apoptosis , ly294002 , protein kinase b , retinal ganglion cell , glaucoma , chemistry , microbiology and biotechnology , retinal , pharmacology , medicine , biology , ophthalmology , biochemistry
Background Glaucoma is the world's second biggest cause of blindness, and patients progressively lose their eyesight. The current clinical treatment for glaucoma involves controlling intraocular pressure with drugs or surgery; however, some patients still progressively lose their eyesight. This treatment is also similar to the treatment of traumatic optic neuropathy. Thus, saving retinal ganglion cells (RGCs) from apoptosis is essential. Methods The role of Acteoside on autophagy modulation in the 661 W cell line. Results In this study, we first find that Acteoside inhibits autophagy, Rapamycin alleviates this inhibition and the PI3K inhibitor, 3‐MA or LY294002, synergistically promotes it. In a mechanistic study, we find that Optineurin (OPTN) mediates Acteoside regulation of autophagy. OPTN overexpression or knockdown activates or inhibits autophagy, respectively. OPTN is inhibited by autophagy inhibitors, such as Acteoside and 3‐MA and is promoted by the autophagy activator, Rapamycin. Meanwhile, PI3K and AKT are elevated by Acteoside and 3‐MA and inhibited by Rapamycin. Finally, we find that Acteoside inhibits apoptosis in parallel to autophagy and that this inhibition is also mediated by OPTN. Conclusion In summary, we conclude that Acteoside inhibits autophagy‐induced apoptosis in RGCs through the OPTN and PI3K/AKT/mTOR pathway, and glaucoma patients may benefit from Acteoside treatment alone or in combination with other autophagy inhibitors.