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环状XPO5通过调控GRIN2A在青光眼外侧膝状体中发挥神经保护作用。

CircXPO5 Plays a Neuroprotective Function in the Lateral Geniculate Nucleus of Glaucoma by Regulating GRIN2A.

作者信息

Yan Zhichao, Lai Mingying, Jia Yu, Deng Caibin, Zhuo Yehong

机构信息

Department of Glaucoma and Neuro-Ophthalmology, Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, School of Optometry, Shenzhen University, Shenzhen 518040, China.

Department of Ophthalmology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.

出版信息

Brain Sci. 2022 Jun 14;12(6):780. doi: 10.3390/brainsci12060780.

Abstract

PURPOSE

Previous studies have found the neurodegeneration and atrophy of glaucomatous lateral geniculate nucleus (LGN), but the mechanism is still unknown. Circular RNA (circRNA) plays some important roles in physiological and pathological progression of the disease. In this study, we focused on the differentially expressed circRNAs and the mechanism for circXPO5 in LGN degeneration in a macaque glaucoma model.

METHODS

Using RNA-seq, we analyzed the differentially expressed circRNAs in a macaque glaucoma model. An RT-QPCR was used to check the expression of selected differentially expressed circRNAs, candidate miRNAs and mRNAs. A competing endogenous RNA (ceRNA) network analysis was performed to examine the mechanism of circXPO5 action.

RESULTS

circXPO5 significantly decreased in the glaucoma model and a ceRNA network analysis revealed that circXPO5 can bind to miR-330-5p, which also binds to GRIN2A (ionotropic receptor NMDA type subunit 2A). QPCR detection showed a decrease in GRIN2A and an increase in miR-330-5p.

CONCLUSIONS

Our earlier studies revealed that the GRIN2A gene regulates the calcium signal pathway. Decreasing of GRIN2A related with neuron apoptosis and neurodegeneration. These findings indicate that the reduction in circXPO5 may have a protective effect on neuronal apoptosis in the visual central system of glaucoma.

摘要

目的

以往研究发现青光眼患者外侧膝状体(LGN)存在神经退行性变和萎缩,但其机制仍不清楚。环状RNA(circRNA)在疾病的生理和病理进展中发挥着重要作用。在本研究中,我们聚焦于猕猴青光眼模型中差异表达的circRNA以及circXPO5在LGN变性中的作用机制。

方法

利用RNA测序技术,我们分析了猕猴青光眼模型中差异表达的circRNA。采用逆转录定量聚合酶链反应(RT-QPCR)检测选定的差异表达circRNA、候选微小RNA(miRNA)和信使核糖核酸(mRNA)的表达。进行竞争性内源RNA(ceRNA)网络分析以研究circXPO5的作用机制。

结果

circXPO5在青光眼模型中显著降低,ceRNA网络分析显示circXPO5可与miR-330-5p结合,而miR-330-5p也与GRIN(离子型谷氨酸受体NMDA2A亚基)结合。QPCR检测显示GRIN2A表达降低,miR-330-5p表达增加。

结论

我们早期的研究表明GRIN2A基因调节钙信号通路。GRIN2A的减少与神经元凋亡和神经退行性变有关。这些发现表明circXPO5的减少可能对青光眼视觉中枢系统的神经元凋亡具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f59/9221081/0a92b26819ef/brainsci-12-00780-g001.jpg

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