Abstract
Purpose: :
Epithelial-mesenchymal transition (EMT), a process whereby differentiated epithelial cells undergo transition to a mesenchymal phenotype, plays a role in embryogenesis, wound healing, carcinogenesis, and tissue fibrosis. Fibrous tissue formation occurs in choroidal neovascular membrane (CNVM) at the late stage of age-related macular degeneration (AMD), and several lines of evidence have suggested the involvement of EMT with CNVM. However, so far the expression of EMT-related transcriptional factors in CNVM has not yet been reported. The purpose of this study is to explore the expression of Snail family, transcriptional factors for EMT, in human CNVM.
Methods: :
Paraffin sections of human CNVM were obtained from Keio University School of Medicine’s tissue sample archives. By immunohistochemistry, EMT-associated transcriptional factors (Snail family) including Snail1, Slug (Snail2), Twist and SIP1 were stained in 12 CNVM specimens of AMD. To better understand the characteristics of the cellular components positively stained with Snail family proteins, RPE65 (specific marker for RPE cells) and -smooth muscle actin (-SMA; marker for mesenchymal cells) were also stained. As a control for RPE staining, the section of postmortem normal human retina were used.
Results: :
Of 12 specimens, 11 CNVM (91.6%) showed the staining for Snail1, which was localized in cellular nuclei. However, the other transcriptional factors, Slug (Snail2), Twist and SIP1 were not detected in CNVM. Nuclear localization of Snail1 was mainly found in the RPE65-positive cells (RPE cells), in particular, stained with -SMA. By contrast, no RPE cells showed the Snail1 staining in normal human retina.
Conclusions: :
The current results are the first to demonstrate the presence of EMT-associated transcriptional factor Snail1 in RPE cells of human CNVM tissues, but not those in normal retina. These data suggest that Snail1 is a pivotal transcriptional factor for EMT in the pathological RPE cells of CNVM.
Keywords: age-related macular degeneration • pathology: human • immunohistochemistry