Transcriptional factors associated with epithelial-mesenchymal transition in choroidal neovascularization

Manabu Hirasawa, Kousuke Noda, Setsuko Noda, Misa Suzuki, Yoko Ozawa, Kei Shinoda, Makoto Inoue, Yoko Ogawa, Kazuo Tsubota, Susumu Ishida

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Purpose: 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.

Original languageEnglish
Pages (from-to)1222-1230
Number of pages9
JournalMolecular vision
Volume17
Publication statusPublished - 2011 May 30

    Fingerprint

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Hirasawa, M., Noda, K., Noda, S., Suzuki, M., Ozawa, Y., Shinoda, K., Inoue, M., Ogawa, Y., Tsubota, K., & Ishida, S. (2011). Transcriptional factors associated with epithelial-mesenchymal transition in choroidal neovascularization. Molecular vision, 17, 1222-1230.