miR-1298通过调控SetD7表达抑制青光眼视网膜神经节细胞生长

MiR-1298 Reduced the Retinal Ganglion Cell Growth in Glaucoma by Regulating SetD7 Expression

目的探索miR-1298调控青光眼视网膜神经节细胞生长及其机制。方法20只C57BL/6小鼠被用于阻断巩膜上静脉建立慢性小鼠青光眼模型。脂多糖诱导Müller细胞作为体外模型,同时转染miR-NC(空白对照组)、miR-1298 mimic、miR-1298 inhibitor、miR-1298 mimic+重组人Set7/9组蛋白甲基转移酶(SetD7)。采用MTT实验、乳酸脱氢酶(LDH)活性和Caspase-3、Caspase-9试剂盒、RT-qPCR和Western blot方法探索miR-1298的功能和机制。结果在青光眼小鼠模型视网膜组织中miR-1298表达量显著提高。上调miR-1298能够抑制Müller细胞增殖和激活LDH活性,下调miR-1298能够促进Müller细胞增殖和减少LDH活性。SetD7是miR-1298调控靶点,激活SetD7可以减弱miR-1298对青光眼视网膜神经节细胞生长的抑制作用。结论miR-1298在青光眼小鼠模型视网膜组织中表达量显著提高,miR-1298能够通过调控SetD7表达抑制青光眼视网膜神经节细胞生长,miR-1298的表达可为青光眼预防和治疗提供参考。

Objective To explore the effect of miR-1298 on the growth of retinal ganglion cells in glaucoma and its mechanism.Methods Chronic glaucoma model was established by blocking the episcleral veins in 20 C57BL/6 mice.In vitro,lipopolysaccharide(LPS)-induced Müller cells were transfected with miR-NC,miR-1298 mimic,miR-1298 inhibitor,and miR-1298 mimic+recombinant human Set7/9 histone methyltransferase(SetD7),respectively.The function and mechanism of miR-1298 in growth of the retinal ganglion cells in glaucoma were tested using MTT kit,LDH kit,Caspase 3 and Caspase 9 kits,RT-qPCR and Western blot.Results MiR-1298 expression was up-regulated in the retina tissue of mice with glaucoma.Upregulation of miR-1298 inhibited Müller cell proliferation and activated LDH activity,while downregulation of miR-1298 promoted Müller cell proliferation and reduced LDH activity.SetD7 was a regulatory target of miR-1298.Activation of SetD7 reduced the inhibitory effect of miR-1298 on the growth of the retinal ganglion cells in glaucoma.Conclusion The expression of miR-1298 is significantly increased in the retina of mice with glaucoma.MiR-1298 may reduce the growth of retinal ganglion cells in glaucoma through suppression of SetD7 expression.The expression of miR-1298 may provide reference for the prevention and treatment of glaucoma.