title: Transcriptional factors associated with epithelial-mesenchymal transition in choroidal neovascularization.
abstract: OBJECTIVE
  To investigate the transcriptional factors associated with epithelial-mesenchymal transition (EMT) in choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).
  
  
  METHODS
  Paraffin sections of CNV obtained from patients with AMD (n = 12) were stained for transcriptional factors related to EMT, i.e., Snail, Slug, SIP1, and Twist. As a control, postmortem sections of ocular normal tissue were used. Furthermore, using a human retinal pigment epithelial (RPE) cell line (ARPE-19), reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence microscopy were performed to explore the cellular localization and expression levels of EMT-associated transcriptional factors upon cytokine stimulation.
  
  
  RESULTS
  Of 12 specimens, 11 CNV tissues (91.6%) showed staining for Snail localized in cellular nuclei, particularly in those of RPE cells. Snail was strongly co-localized with α-smooth muscle antigen (SMA) in RPE cells. In contrast, postmortem human retina showed no Snail staining in RPE cells. Other transcriptional factors, Slug, Twist and SIP1 were not detected in CNV or normal human retina. In ARPE-19 cells, RT-PCR and immunofluorescence microscopy showed that Snail mRNA was upregulated by transforming growth factor (TGF)-β and VEGF stimulation. Furthermore, TGF-β induced relocalization of Snail to the nucleus in RPE cells.
  
  
  CONCLUSIONS
  The current data indicate that Snail is a major transcriptional factor for EMT changes of RPE cells in human CNV.
authors: Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan
authors: Manabu
authors: M
authors: Hirasawa
authors: Kousuke
authors: K
authors: Noda
authors: Setsuko
authors: S
authors: Noda
authors: Misa
authors: M
authors: Suzuki
authors: Yoko
authors: Y
authors: Ozawa
authors: Kei
authors: K
authors: Shinoda
authors: Makoto
authors: M
authors: Inoue
authors: Yoko
authors: Y
authors: Ogawa
authors: Kazuo
authors: K
authors: Tsubota
authors: Susumu
authors: S
authors: Ishida
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