Silencing of GAS5 Alleviates Glaucoma in Rat Models by Reducing Retinal Ganglion Cell Apoptosis
Silencing of GAS5 Alleviates Glaucoma in Rat Models by Reducing Retinal Ganglion Cell Apoptosis
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GAS5 沉默可通过减少视网膜神经节细胞凋亡来减轻大鼠模型中的青光眼
DOI：
10.1089/hum.2019.056
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发表时间：
2019
影响因子：
4.2
通讯作者：
Ji Dan
中科院分区：
文献类型：
--
作者：
Zhou Rong-Rong;Li Hai-Bo;You Qi-Sheng;Rong Rong;You Meng-Ling;Xiong Kun;Huang Ju-Fang;Xia Xiao-Bo;Ji Dan
视网膜神经节细胞（RGC）在青光眼的发病和发展中起着关键作用。本研究旨在探讨长链非编码RNA生长抑制特异性转录本5（GAS 5）通过调控视网膜节细胞凋亡在青光眼发生发展中的作用机制。采用经角膜缘激光光凝法成功建立了大鼠慢性青光眼模型。取视网膜组织，甲苯胺蓝染色测定RGCs密度。将GAS 5或EZH2的过表达载体或短发夹RNA转染体外加压培养的RGC，检测GAS 5在RGC凋亡中的作用。进一步鉴定了EZH2和ATP结合盒转运体A1（ABCA1）的参与。流式细胞仪检测激光处理和转染后细胞凋亡情况。我们发现青光眼大鼠视网膜组织中GAS 5表达丰富，RGC密度降低。GAS5的沉默导致RGC中EZH2表达增加和ABCA 1表达减少。此外，EZH2的上调促进组蛋白H3上赖氨酸27的三甲基化，从而抑制ABCA 1表达并最终导致RGC凋亡的抑制。这些发现为进一步了解GAS 5在RGC凋亡中的作用提供了依据。我们的结论是下调GAS5可以帮助缓解青光眼症状。因此，GAS 5是开发用于治疗青光眼患者的新型治疗方法的有希望的靶点。
Retinal ganglion cells (RGCs) play a key role in the pathogenesis and development of glaucoma. The present study aims to investigate the underlying mechanism of long noncoding RNA growth arrest-specific transcript 5 (GAS5) in glaucoma development through regulating the apoptosis of RGCs. Rat models of chronic glaucoma were successfully established by translimbal laser photocoagulation. Retinal tissues were collected to determine the density of RGCs through Toluidine blue staining. The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) was transfected into RGCs afterin vitropressurization culture to examine the function of GAS5 in RGC apoptosis. The involvement of EZH2 and ATP-binding cassette transporter A1 (ABCA1) was further identified. Cell apoptosis after laser treatment and transfection was assessed by flow cytometry. We found abundant GAS5 expression and a reduction in RGC density in the retinal tissues of glaucoma rats. Silencing of GAS5 led to increased EZH2 expression and decreased ABCA1 expression in RGCs. In addition, upregulation of EZH2 promoted trimethylation of lysine 27 on histone H3, thereby suppressing ABCA1 expression and eventually leading to the inhibition of RGC apoptosis. These findings provide further understanding of the function of GAS5 in RGC apoptosis. We conclude that downregulation of GAS5 could help relieve glaucoma symptoms. GAS5 is therefore a promising target for developing novel therapeutic approaches for treating patients with glaucoma.