Wnt/beta-Catenin Signaling Mediates Regeneration of Retinal Pigment Epithelium After Laser Photocoagulation in Mouse Eye
- Authors
- Han, Jung Woo; Lyu, Jungmook; Park, Yeo Jin; Jang, Sun Young; Park, Tae Kwann
- Issue Date
- Dec-2015
- Publisher
- Association for Research in Vision and Ophthalmology
- Keywords
- retinal pigment epithelium (RPE); Wnt/beta-catenin signaling pathway; laser photocoagulation; epithelial-mesenchymal transition (EMT)
- Citation
- Investigative Ophthalmology and Visual Science, v.56, no.13, pp 8314 - 8324
- Pages
- 11
- Journal Title
- Investigative Ophthalmology and Visual Science
- Volume
- 56
- Number
- 13
- Start Page
- 8314
- End Page
- 8324
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10070
- DOI
- 10.1167/iovs.15-18359
- ISSN
- 0146-0404
1552-5783
- Abstract
- PURPOSE. Laser photocoagulation of retinal pigment epithelium (RPE) is used to stimulate the regenerative processes of the RPE. However, the molecular mechanisms that control RPE proliferation and the epithelial-mesenchymal transition (EMT) during regeneration remain poorly understood. We investigated the role of Wnt/beta-catenin signaling in the regeneration of mouse RPE after laser photocoagulation. METHODS. C57BL/6J mice were photocoagulated unilaterally. To determine the beta-catenin-dependent Wnt signal transduction in the photocoagulated RPE, the expression levels of Wnts, beta-catenin, and their target genes were analyzed using real time-PCR and Western blotting. Retinal pigment epithelium proliferation and EMT were determined by 5-ethynyl-2'--deoxyuridine (EdU) incorporation assay and by profiling expression of EMT markers, respectively, in eyes injected intravitreally with a Wnt/beta-catenin signaling antagonist, Dkk-1, after laser photocoagulation. RESULTS. Expression of several of the 19 Wnt genes was significantly increased in laser-treated RPE. The expression levels of beta-catenin signaling target genes cyclin D1, Otx2, and Mitf were higher in laser-treated RPE than in control RPE. The number of EdU-positive cells in the laser-treated area was significantly lower in the Dkk-1-injected group than in the laser-treated group or laser-treated + vehicle-injected group. There were more Otx2- and Mitf-positive cells after laser photocoagulation and markedly fewer in the Dkk-1-injected group. Otx2- and Mitf-positive cells were colocalized with EdU-positive cells. The EMT markers vimentin and alpha-smooth muscle actin (alpha-SMA) were upregulated in the laser-treated area and significantly downregulated in the Dkk-1-injected group. CONCLUSIONS. Laser photocoagulation activates a Wnt/beta-catenin signal transduction pathway, promoting both RPE proliferation and EMT. Wnt/beta-catenin signaling also upregulates the expression of Otx2 and Mitf, key transcription factors in RPE formation. Our results demonstrate an important role for Wnt/beta-catenin signaling in RPE proliferation and EMT, and suggest that manipulating Wnt/beta-catenin signaling may have therapeutic potential for RPE regeneration.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Ophthalmology > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10070)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.