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Iori Wada, Shintaro Nakao, Keijiro Ishikawa, Muneo Yamaguchi, Mitsuru Arima, Yoshihiro Kaizu, Tatsuro Ishibashi, Koh-hei Sonoda; ROCK inhibitor Ripasudil reverses phenotype from EMT to MET in subretinal fibrosis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4913.
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Subretinal fibrosis is known to be developed occasionally in neovascular age-related macular degeneration after anti-VEGF therapy. We have reported that ROCK inhibitor ripasudil could suppress the subretinal fibrosis. The purpose of this study was to investigate the impact of ROCK inhibitor on epithelial-to-mesenchymal transition (EMT) / mesenchymal-to-epithelial transition (MET) in the subretinal fibrosis related to choroidal neovascularization (CNV).
C57BL/6J mice underwent laser photocoagulation to induce CNV-related fibrosis. Ripasudil (30 μmol/L) were treated intravitreally every 3 days from the 14th day after laser injury and harvested after the 21th day. The subretinal fibrosis was specifically captured by laser microdissection (LMD) and quantified EMT/MET-associated genes by RT-PCR. Moreover, human retinal pigment epithelium (hRPE) cells were stimulated by TGFβ2 with or without ripasudil (0.3/3/30 μmol/L) and EMT/MET-associated genes were also examined using RT-PCR.
The EMT-associated genes, TGFβ2 and α-SMA, were confirmed the significant upregulation at the part of subretinal fibrosis without treatment (P<0.05). However, these genes were significantly suppressed by ripasudil at the part of subretinal fibrosis (P<0.05). In vitro, ripasudil (30 μmol/L) significantly suppressed α-SMA gene and additionally significantly upregulated the MET-associated genes, E-cadherin and c-Myc.
ROCK inhibitior ripasudil has the therapeutic potential for CNV-related subretinal fibrosis by reversing the phenotype of EMT/MET.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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