Biochemical alterations in the retinas of very low-density lipoprotein receptor knockout mice - An animal model of retinal angiomatous proliferation
Biochemical alterations in the retinas of very low-density lipoprotein receptor knockout mice - An animal model of retinal angiomatous proliferation
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DOI：
10.1001/archopht.125.6.795
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发表时间：
2007-06-01
影响因子：
--
通讯作者：
Cao, Wei
中科院分区：
文献类型：
--
作者：
Li, Chao;Huang, Zhong;Cao, Wei
目的：在视网膜血管瘤增殖的动物模型中，鉴定和描述极低密度脂蛋白受体（VLDLr）基因敲除小鼠视网膜的生化改变。免疫组化分析、Western印迹分析、逆转录-聚合酶链反应、和电泳迁移率变动分析用于鉴定和表征改变的基因和蛋白质表达以及参与发病机制的信号级联反应结果：VLDLr小鼠视网膜病变区血管生成因子血管内皮生长因子和碱性成纤维细胞生长因子的表达明显增强，病变区周围的Muller细胞被激活，表现为胶质细胞酸性蛋白表达增加。促炎细胞因子IL-18（白细胞介素18）和炎症介质细胞间粘附分子-1的表达增加之前，显着的视网膜内新生血管。此外，Akt和丝裂原活化蛋白激酶的磷酸化和核因子κ B的转位在VLDLr敲除小鼠视网膜中更大。结论：炎症过程参与VLDLr敲除小鼠视网膜中新血管的发展。临床相关性：了解VLDLr基因敲除小鼠视网膜中这些生化改变的分子机制将为开发新的抗VLDLr基因敲除小鼠提供基础。视网膜血管瘤增生的治疗方法。
Objective: To identify and characterize biochemical alterations in the retinas of very low-density lipoprotein receptor ( VLDLr) knockout mice in an animal model of retinal angiomatous proliferation.Methods: Immunohistochemical analysis, Western blot analysis, reverse transcriptase-polymerase chain reaction, and electrophoretic mobility shift assay were used to identify and characterize the altered gene and protein expression as well as signal cascades involved in the pathogenesis of neovascularization in the retinas of VLDLr mice.Results: Expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor was significantly greater in the lesion area, and Muller cells around the lesion area were activated, as indicated by increased expression of glial fibrillary acidic protein. Expression of the proinflammatory cytokine IL-18 ( interleukin 18) and the inflammation mediator intercellular adhesion molecule-1 was increased before significant intraretinal neovascularization. Furthermore, phosphorylation of Akt and mitogen-activated protein kinase and translocalization of nuclear factor kappa B were greater in VLDLr knockout mouse retinas.Conclusion: An inflammatory process is involved in the development of neovascularization in the VLDLr knockout mouse retina.Clinical Relevance: Understanding the molecular mechanisms underlying these biochemical alterations in the retinas of VLDLr knockout mice will provide a foundation for developing novel therapeutic approaches to retinal angiomatous proliferation.