Inhibition of Retinal Ganglion Cell Loss By a Novel ROCK Inhibitor (E212) in Ischemic Optic Nerve Injury Via Antioxidative and Anti-Inflammatory Actions

doi:10.1167/iovs.62.6.21

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23589

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題名:	Inhibition of Retinal Ganglion Cell Loss By a Novel ROCK Inhibitor (E212) in Ischemic Optic Nerve Injury Via Antioxidative and Anti-Inflammatory Actions
作者:	Wen, YT;Huang, CW;Liu, CP;Chen, CH;Tu, CM;Hwang, CS;Chen, YH;Chen, WR;Lin, KL;Ho, YC;Chen, TC;Tsai, RK
關鍵詞:	Rho kinase inhibitor;ischemic optic neuropathy;reactive oxygen species;retinal ganglion cell;blood-retinal barrier
日期:	2021
上傳時間:	2022-08-05T09:39:43Z (UTC)
出版者:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
ISSN:	0146-0404
摘要:	PURPOSE. This study investigated the neuroprotective effects of administration of ROCK inhibitor E212 on ischemic optic neuropathy. METHODS. Rats received an intravitreal injection of either E212 or PBS immediately after optic nerve infarct. The oxidative stress in the retina was detected by performing super-oxide dismutase activity and CellROX assays. The integrity of retinal pigment epithelium was determined by staining of zona occludens 1. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined by using flash visual-evoked potential analysis, retrograde FluoroGold labeling, and TdT-dUTP nick end-labeling assay. Macrophage infiltration was detected by staining for ED1. The protein levels of TNF-alpha, p-CRMP, p-AKT1, p-STAT3, and CD206 were evaluated using Western blotting. RESULTS. Administration of E212 resulted in a 1.23-fold increase in the superoxide dismutase activity of the retina and 2.28-fold decrease in RGC-produced reactive oxygen species as compared to the levels observed upon treatment with PBS (P < 0.05). Moreover, E212 prevented the disruption of the blood-retinal barrier (BRB) in contrast to PBS. The P1-N2 amplitude and RGC density in the E212-treated group were 1.75- and 2.05-fold higher, respectively, than those in the PBS-treated group (P < 0.05). The numbers of apoptotic RGCs and macrophages were reduced by 2.93- and 2.54-fold, respectively, in the E212-treated group compared with those in the PBS-treated group (P < 0.05). The levels of p-AKT1, p-STAT3, and CD206 were increased, whereas those of p-PTEN, p-CRMP2, and TNF-alpha were decreased after treatment with E212 (P < 0.05). CONCLUSIONS. Treatment with E212 suppresses oxidative stress, BRB disruption, and neuroinflammation to protect the visual function in ischemic optic neuropathy.
URI:	http://dx.doi.org/10.1167/iovs.62.6.21 https://www.webofscience.com/wos/woscc/full-record/WOS:000685196300014 https://ir.csmu.edu.tw:8080/handle/310902500/23589
關聯:	INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE ,2021,v62,issue 6
顯示於類別:	[中山醫學大學研究成果] 期刊論文

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