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经角膜电刺激可抑制急性高眼压损伤后视网膜小胶质细胞的激活并提高视网膜神经节细胞的存活率。

Transcorneal Electrical Stimulation Inhibits Retinal Microglial Activation and Enhances Retinal Ganglion Cell Survival After Acute Ocular Hypertensive Injury.

作者信息

Fu Lin, Fung Frederic K, Lo Amy Cheuk-Yin, Chan Yau-Kei, So Kwok-Fai, Wong Ian Yat-Hin, Shih Kendrick Co, Lai Jimmy Shiu-Ming

机构信息

Affiliated Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.

Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR.

出版信息

Transl Vis Sci Technol. 2018 May 29;7(3):7. doi: 10.1167/tvst.7.3.7. eCollection 2018 May.

Abstract

PURPOSE

To investigate the effect of transcorneal electrical stimulation (TcES) on retinal ganglion cell (RGC) function and survival after acute ocular hypertension-related retinal injury in gerbil eyes.

METHODS

Gerbil eyes were subjected to acute ocular hypertensive injury (80 mm Hg for 60 minutes). In the treatment group, TcES was applied to the surgical eye immediately and then twice weekly for a total of 1 month. In the control group, sham TcES was given to the surgical eye at the same time points. Retinal function was assessed and compared between groups using flash electroretinography. For histological analysis, the number of RGC and microglial cells were counted by immunofluorescence staining after the gerbils were sacrificed on day 7 and day 28. Real-time polymerase chain reaction and western blot analysis were conducted to compare expression of interleukin (IL)-10, IL-6, COX-2, tumor necrosis factor (TNF)-α, and NF-κB phosphorylation among groups.

RESULTS

TcES-treated eyes had significantly higher RGC survival at 1 month compared to controls. This was associated with RGC function. Furthermore, TcES-treated eyes were shown to have increased IL-10 expression, with a corresponding reduction in IL-6 and COX-2 expression as well as reduction in NF-κB phosphorylation. This was associated with a suppression in microglial cell activation in TcES-treated eyes.

CONCLUSIONS

Early treatment with TcES in gerbils protected the RGC from secondary damage and preserved retinal function in acute ocular hypertensive injury through modulation of the microglial-cell activated local inflammatory response.

TRANSLATIONAL RELEVANCE

Our study strengthens the argument for translating TcES as a viable treatment in acute glaucoma.

摘要

目的

探讨经角膜电刺激(TcES)对沙鼠眼急性高眼压相关视网膜损伤后视网膜神经节细胞(RGC)功能及存活的影响。

方法

对沙鼠眼施加急性高眼压损伤(80 mmHg,持续60分钟)。治疗组在手术眼立即进行TcES治疗,然后每周两次,共1个月。对照组在相同时间点对手术眼进行假TcES治疗。使用闪光视网膜电图评估并比较两组之间的视网膜功能。为进行组织学分析,在第7天和第28天处死沙鼠后,通过免疫荧光染色计数RGC和小胶质细胞的数量。进行实时聚合酶链反应和蛋白质印迹分析以比较各组中白细胞介素(IL)-10、IL-6、环氧化酶-2(COX-2)、肿瘤坏死因子(TNF)-α和核因子κB(NF-κB)磷酸化的表达。

结果

与对照组相比,TcES治疗的眼睛在1个月时RGC存活率显著更高。这与RGC功能相关。此外,TcES治疗的眼睛显示IL-10表达增加,同时IL-6和COX-2表达相应降低以及NF-κB磷酸化降低。这与TcES治疗的眼睛中小胶质细胞活化的抑制有关。

结论

沙鼠早期使用TcES治疗可保护RGC免受继发性损伤,并通过调节小胶质细胞活化的局部炎症反应在急性高眼压损伤中保留视网膜功能。

转化相关性

我们的研究强化了将TcES作为急性青光眼可行治疗方法进行转化的论据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3758/5976234/ddfc9526383d/i2164-2591-7-3-7-f01.jpg

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