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IR@PKUHSC  > 北京大学第二临床医学院  > 眼科  > 期刊论文
学科主题: 临床医学
题名:
Evidence for enhanced tissue factor expression in age-related macular degeneration
作者: 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
发表日期: 2011-04-01
DOI: 10.1038/labinvest.2010.184
卷: 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
项目资助者: National Eye Institute, National Institutes of Health
WOS记录号: WOS:000288937400004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66794
Appears in Collections:北京大学第二临床医学院_眼科_期刊论文

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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

Recommended Citation:
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.
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