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Evidence for enhanced tissue factor expression in age-related macular degeneration
Cho, Youngeun1; Cao, Xiaoguang1,2; Shen, DeFen1; Tuo, Jingsheng1; Parver, Leonard M.3; Rickles, Frederick R.4,5,6; Chan, Chi-Chao1
关键词age-related macular degeneration inflammation oxidative stress retina retinal pigment epithelium tissue factor
刊名LABORATORY INVESTIGATION
2011-04-01
DOI10.1038/labinvest.2010.184
91期:4页:519-526
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental ; Pathology
研究领域[WOS]Research & Experimental Medicine ; Pathology
关键词[WOS]CHOROIDAL NEOVASCULARIZATION ; ENDOTHELIAL-CELLS ; MOUSE MODEL ; FACTOR GENE ; ANGIOGENESIS ; THROMBOSIS ; DRUSEN ; INFLAMMATION ; DISEASE ; IMMUNOTHERAPY
英文摘要

Tissue factor (TF) is the primary initiator of blood coagulation. In addition to hemostasis, TF can initiate intracellular signaling and promote inflammation and angiogenesis, the key processes underlying the pathogenesis of age-related macular degeneration (AMD). AMD, the leading cause of irreversible blindness among the elderly, involves many genetic and environmental risk factors, including oxidative stress and inflammation. In this study, TF expression was examined in human AMD tissue and in the eyes of a model of AMD, the Ccl2(-/-)/Cx3cr1(-/-) (DKO) mouse, as well as in the ARPE-19 cell line after lipopolysaccharide (LPS) and H(2)O(2) stimulation. Total RNA was extracted from tissue samples and further analyzed by real-time RT-PCR. Immunohistochemistry was performed to evaluate TF protein expression. In the human retina, a 32-fold increase of TF mRNA expression was detected in AMD macular lesions compared with normal maculae. TF protein expression was also enhanced in human AMD maculae. Similarly, TF transcript and protein expression were moderately increased in retinal lesions, neuroretinal tissue, and cultured RPE cells of DKO mice compared with age-matched wild-type mice. TF expression level correlated with age in both wild-type and DKO mice. In order to better understand how AMD might lead to enhanced TF expression, 1, 5, and 10 mu g/ml LPS as well as 100 and 200 mu M H(2)O(2) were used to stimulate ARPE-19 cells for 24 and 2 h, respectively. LPS treatment consistently increased TF transcript and protein expression. H(2)O(2) alone or in combination with LPS also moderately enhanced TF expression. These results indicate that upregulated TF expression may be associated with AMD, and inflammatory and oxidative stress may contribute to TF expression in AMD eyes. Laboratory Investigation (2011) 91, 519-526; doi:10.1038/labinvest.2010.184; published online 1 November 2010

语种英语
WOS记录号WOS:000288937400004
资助机构National Eye Institute, National Institutes of Health
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被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66794
专题北京大学第二临床医学院_眼科
作者单位1.NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA
2.Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China
3.Georgetown Univ, Sch Med, Dept Ophthalmol, Washington, DC USA
4.George Washington Univ, Sch Med & Hlth Sci, Dept Med, Washington, DC 20052 USA
5.George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA
6.George Washington Univ, Sch Med & Hlth Sci, Dept Physiol & Pharmacol, Washington, DC 20052 USA
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Cho, Youngeun,Cao, Xiaoguang,Shen, DeFen,et al. Evidence for enhanced tissue factor expression in age-related macular degeneration[J]. LABORATORY INVESTIGATION,2011,91(4):519-526.
APA Cho, Youngeun.,Cao, Xiaoguang.,Shen, DeFen.,Tuo, Jingsheng.,Parver, Leonard M..,...&Chan, Chi-Chao.(2011).Evidence for enhanced tissue factor expression in age-related macular degeneration.LABORATORY INVESTIGATION,91(4),519-526.
MLA Cho, Youngeun,et al."Evidence for enhanced tissue factor expression in age-related macular degeneration".LABORATORY INVESTIGATION 91.4(2011):519-526.
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