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Abstract #84393 Published in IGR 21-1

Silencing of GAS5 Alleviates Glaucoma in Rat Models by Reducing Retinal Ganglion Cell Apoptosis

Zhou RR; Li HB; You QS; Rong R; You ML; Xiong K; Huang JF; Xia XB; Ji D
Human Genetics and Therapeutics 2019; 30: 1505-1519

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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 after pressurization 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.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.

Full article

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Classification:

11.8 Neuroprotection (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)

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