眼科新进展2026，Vol.46Issue(1)：23-30,8.DOI:10.13389/j.cnki.rao.2026.0005
线粒体能量代谢指标与糖尿病视网膜病变的潜在关系
Potential relationship between mitochondrial energy metabolism index and diabetic retinopathy
摘要
Abstract
Objective To explore the potential relationship between the mitochondrial intima 44 homologue(TIMM44)and diabetic retinopathy(DR).Methods The human retinal pigment epithelial(RPE)cell line ARPE-19 was divided into a blank group,a mannose group,a high glucose(HG)group,a HG+TIMM44 group,and a HG+TIMM44+RS-VA405 group.Cell viability was detected by the CCK-8 assay kit,and mitochondrial membrane potential was measured by the JC-1 assay kit.After human retinal endothelial cells were co-cultured with conditioned medium from different groups of ARPE-19 cells,the angiogenesis in the human retinal endothelial cells in each group was assessed.Twenty-four C57BL/6J mice were randomly divided into a control group,a streptozotocin(STZ)group,a STZ+TIMM44 group,and a STZ+TIMM44+RSVA405 group.Reactive oxygen species(ROS)levels,ATP synthase activity,and relative mitochondrial DNA(mtDNA)copy numbers in cells or mouse retinal tissues in each group were detected by assay kits and quantitative real-time polymerase chain reaction.The expressions of TIMM44,serine/threonine kinase AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR),and mitochondrial dysfunction related proteins were detected by west-ern blot.Results Compared with the HG group,the ARPE-19 cell viability,ATP synthase activity,mtDNA copy number,JC-1 ratio,and p-mTOR protein levels in the HG+TIMM44 group significantly increased(all P<0.05),while the ROS levels and the protein expression of cleaved caspase3,cyt-c,and p-AMPKsignificantly decreased(all P<0.05).The cell viability,ATP synthase activity,mtDNA copy number,JC-1 ratio,and Bcl-2 protein expression in ARPE-19 cells in the HG+TIMM44+RSVA405 group were significantly downregulated,while the ROS levels and the protein expression of cleaved caspase 3,cyt-c,and p-AMPK were significantly upregulated compared to the HG+TIMM44 group(all P<0.05).Compared with the HG group,the number of vascular branches formed by human retinal endothelial cells in the HG+TIMM44 group was signifi-cantly downregulated(P<0.05).The number of vascular branches formed by human retinal endothelial cells in the HG+TIMM44+RSVA405 group was significantly upregulated compared to the HG+TIMM44 group(P<0.05).Compared with the STZ group,the STZ+TIMM44 group showed significantly upregulated mouse retinal thickness,ATP synthase activity,mtDNA copy number,and Bcl-2 protein expression and significantly downregulated ROS levels(all P<0.05).The mouse retinal thickness,ATP synthase activity,mtDNA copy number,and Bcl-2 protein expression in the STZ+TIMM44+RSVA405 group were significantly downregulated,while ROS levels were significantly upregulated compared to the STZ+TIMM44 group(all P<0.05).Conclusion TIMM44 improves RPE mitochondrial dysfunction induced by HG exposure in vitro and in vivo by inhibiting the AMPK/mTOR signaling pathway.关键词
线粒体内膜44同源物/糖尿病视网膜病变/视网膜色素上皮细胞/线粒体/AMPK/mTOR信号通路Key words
mitochondrial intima 44 homologue/diabetic retinopathy/retinal pigment epithelial cells/mitochondrion/AMP-activated protein kinase/mammalian target of rapamycin signaling pathway分类
医药卫生引用本文复制引用
LUO Xingmei,DENG Li,LI Ling,CAI Xiaoli,YI Mian,LIU Xia,ZHAO Jing..线粒体能量代谢指标与糖尿病视网膜病变的潜在关系[J].眼科新进展,2026,46(1):23-30,8.基金项目
湖南省卫生健康委科研计划项目(编号:D202307026842) （编号:D202307026842）
