Objective To explore the role of the base mismatch repair gene Mutyh in retinopathy of prematurity(ROP). Methods Mutyh(-/-)and wild-type(WT)mice were used for the modeling of oxygen-induced retinopathy.The retinal oxidative stress was examined,and the ultrastructures of photoreceptors and mitochondria were observed.The biomarkers of photoreceptors and mitochondria were tested.Furthermore,the photoreceptor cell line 661W was treated with hydrogen peroxide for the modeling of oxidative stress.In the cell model,and the oxidative stress and photoreceptor functions in the cells were measured. Results In both the mouse and cell models,the expression of Mutyh was up-regulated.Mutyh knockout in mice and knockdown in cells exerted negative effects on photoreceptors and mitochondria.Mutyh overexpression showed protective functions in the cell model,indicating that Mutyh played a role in repairing photoreceptors and mitochondria. Conclusions Mutyh showed the potential to become a biomarker of ROP.Increasing Mutyh expression might have therapeutic effects on ROP,which needs further validation.
目的 探究碱基错配修复基因Mutyh在早产儿视网膜病变(ROP)中的潜在作用。方法 取Mutyh敲除小鼠和野生型小鼠,构建氧诱导的视网膜病变模型,检测视网膜氧化应激水平,观察感光细胞及线粒体超微结构,检测相应生物标志物;体外应用过氧化氢刺激小鼠感光细胞系661W,构建氧化应激模型,检测感光细胞氧化应激水平及线粒体功能。结果 Mutyh在小鼠氧诱导的视网膜病变模型及661W氧化应激模型中表达量升高,Mutyh动物敲除和细胞敲减实验均显示感光细胞和线粒体损伤加重,而体外过表达Mutyh能够修复感光细胞和线粒体损伤。结论 Mutyh有潜力成为ROP的生物标志物,通过提升Mutyh的表达,可能对ROP发挥治疗作用。.
Keywords: Mutyh; oxidative stress; oxygen-induced retinopathy; photoreceptor; retinopathy of prematurity.