Evidence for enhanced tissue factor expression in age-related macular degeneration

Youngeun Cho, Xiaoguang Cao, Defen Shen, Jingsheng Tuo, Leonard M. Parver, Frederick R. Rickles, Chi Chao Chan

Research output: Contribution to journalArticlepeer-review

Abstract

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 H2O2 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 μg/ml LPS as well as 100 and 200 μM H2O2 were used to stimulate ARPE-19 cells for 24 and 2 h, respectively. LPS treatment consistently increased TF transcript and protein expression. H2O 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.

Original languageEnglish (US)
Pages (from-to)519-526
Number of pages8
JournalLaboratory Investigation
Volume91
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • age-related macular degeneration
  • inflammation
  • oxidative stress
  • retina
  • retinal pigment epithelium

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Evidence for enhanced tissue factor expression in age-related macular degeneration'. Together they form a unique fingerprint.

Cite this