LncRNA MEG3 promotes glaucomatous retinal ganglion cell apoptosis via upregulating miR-106 target gene caspase-8

Abstract

Background: MiR-106b and caspase-8 played a key role in the development of acute glaucoma. Increasing evidence has indicated that long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) participated in regulating pathophysiological processes. However, the association among MEG3, miR-106b and caspase-8 remained unclear. Methods: We employed the mouse model of acute glaucoma and oxygen and glucose deprivation (OGD)/reoxygenation cellular model for in vivo and in vitro experiments. The miRNA inhibitor and small interfering RNA (siRNA) were transfected into primary retinal ganglion cells (RGCs) for miRNA and lncRNA knockdown. The interaction among MEG3, miR-106b and caspase-8 was assessed by RNA immunoprecipitation, RNA pull down and luciferase reporter assay. The changes in gene expression were assessed by quantitative Real-Time PCR (qRT-PCR) and western blot. Cell apoptosis analysis was performed using flow cytometry. Results: MEG3 expression was increased in the mouse model of acute glaucoma and OGD-treated RGCs. MEG3 knockdown alleviated RGC apoptosis following OGD. RNA immunoprecipitation and RNA pull down displayed that MEG3 directly targeted miR-106b, while luciferase reporter assay confirmed the interaction between miR-106b and caspase-8. MEG3 silencing significantly relieved RGC apoptosis via downregulating miR-106b target gene caspase-8. Conclusion: MEG3 increased the apoptosis of glaucomatous RGC via miR-106b/caspase-8 axis. Keywords:  acute glaucoma; retinal ganglion cells; MEG3; miR-106b; caspase-8