Wnt信号在年龄相关性黄斑变性组织和小鼠模型中的表达及作用

Expression and Role of Wnt Signal in Age-Related Macular Degeneration Tissues and Mouse Models

为了考察Wnt信号在年龄相关性黄斑变性组织和小鼠模型中的表达及作用,本研究采用免疫组织化学染色检测了10例干性年龄相关性黄斑变性病例和10例年龄相匹配的正常眼睛石蜡切片中LRP6和β-catenin的表达。通过氢醌诱导小鼠干性年龄相关性黄斑变性模型,然后应用Wnt信号通路抑制剂ICG001治疗模型小鼠4周。采用苏木精和曙红染色检测视网膜病理改变,并对小鼠进行视网膜病变评分。采用RT-PCR和Western blotting检测视网膜组织中Wnt信号及靶基因(LRP6,β-catenin,c-MYC,VEGF,ICAM-1,TNF-α和HIF-1)的表达。研究显示,与正常视网膜组织相比,干性年龄相关性黄斑变性患者视网膜组织中的LRP6、β-catenin、c-MYC、VEGF、ICAM-1、TNF-α和HIF-1的mRNA和蛋白表达显著升高。Wnt信号通路抑制剂ICG001显著减轻了小鼠的视网膜病变并降低了视网膜病变评分。与模型组相比,ICG001治疗组的小鼠视网膜组织中LRP6、β-catenin、c-MYC、VEGF、ICAM-1、TNF-α和HIF-1的表达均明显降低。本研究表明,在干性年龄相关性黄斑变性的患者和动物模型中Wnt信号被异常激活,靶向抑制Wnt信号可通过减弱氧化应激、抑制炎症反应、调节血管生成来改善视网膜的结构和功能。

To investigate the expression and role of Wnt signaling in age-related macular degeneration tissues and mouse models,in this study,immunohistochemical staining was used to detect the expression of LRP6 andβ-catenin in 10 cases of dry age-related macular degeneration and 10 age-matched normal eye paraffin sections.Models of dry age-related macular degeneration in mice were induced by hydroquinone,and then model mice were treated with the Wnt signaling pathway inhibitor ICG001 for 4 weeks.Hematoxylin and eosin staining were used to detect retinal pathological changes,and mice were scored for retinopathy.RT-PCR and Western blot were used to detect the expression of Wnt signals and target genes(LRP6,β-catenin,c-MYC,VEGF,ICAM-1,TNF-αand HIF-1)in retinal tissue.Studies showed that mRNA and protein expressions of LRP6,β-catenin,c-MYC,VEGF,ICAM-1,TNF-α,and HIF-1 in retinal tissue of patients with dry age-related macular degeneration significantly increased compared to normal retinal tissue.Wnt signaling pathway inhibitor ICG001 significantly reduced retinopathy and lowered the retinopathy score in mice.Compared with the model group,the expression of LRP6,β-catenin,c-MYC,VEGF,ICAM-1,TNF-αand HIF-1 in the retinal tissue of the mice treated with ICG001 was significantly reduced.This study indicates that Wnt signaling is abnormally activated in patients and animal models of dry age-related macular degeneration.Targeted inhibition of Wnt signals can improve the structure and function of the retina by reducing oxidative stress,suppressing inflammatory responses,and regulating angiogenesis.