Investigative ophthalmology & visual science · 2026
RPE With ROCK-Mediated Epithelial-Mesenchymal Transition as a Key Contributor of Subretinal Fibrosis in AMD.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Wada Iori, Ishikawa Keijiro, Yamaguchi Muneo, Shimokawa Shotaro, Rui Ji, Mori Kenichiro, Kaizu Yoshihiro, Arima Mitsuru, Notomi Shoji, Murakami Yusuke, Inagaki Shigenori, Kohro Yuta, Tsuda Makoto, Shibata Kensuke, Terao Ryo, Terabayashi Takeshi, Ishizaki Toshimasa, Yoshida Shigeo, Ishibashi Tatsuro, Ishida Susumu, Apte Rajendra S, Sonoda Koh-Hei, Nakao Shintaro
Аннотация
PURPOSE: To investigate the cellular origin and molecular mechanisms underlying subretinal fibrosis (SRF) in neovascular AMD (nAMD), with a focus on the role of RPE and Rho-associated coiled-coil-containing protein kinase (ROCK)-mediated epithelial-mesenchymal transition (EMT).
METHODS: Fate-mapping with lineage tracing, laser capture microdissection, microarray and RT-PCR analyses, immunohistochemistry, and functional assays with ROCK inhibitors (Ripasudil, Belumosudil) were used to assess EMT/endothelial-to-mesenchymal transition contributions to SRF and ROCK pathway involvement.
RESULTS: Fate mapping identified RPE and endothelial cells as sources of myofibroblasts. EMT-related gene upregulation and ROCK1/2 expression were observed in SRF lesions. RPE-specific ROCK2 knockout significantly reduced fibrosis and EMT markers. Ripasudil suppressed SRF development and reversed EMT both in vivo and in vitro. ROCK expression was confirmed in human choroidal neovascularization membranes.
CONCLUSIONS: RPE-derived myofibroblasts via ROCK2-mediated EMT play a dominant role in SRF formation. ROCK inhibitors, particularly Ripasudil, may serve as effective therapeutic agents against fibrosis in nAMD.
METHODS: Fate-mapping with lineage tracing, laser capture microdissection, microarray and RT-PCR analyses, immunohistochemistry, and functional assays with ROCK inhibitors (Ripasudil, Belumosudil) were used to assess EMT/endothelial-to-mesenchymal transition contributions to SRF and ROCK pathway involvement.
RESULTS: Fate mapping identified RPE and endothelial cells as sources of myofibroblasts. EMT-related gene upregulation and ROCK1/2 expression were observed in SRF lesions. RPE-specific ROCK2 knockout significantly reduced fibrosis and EMT markers. Ripasudil suppressed SRF development and reversed EMT both in vivo and in vitro. ROCK expression was confirmed in human choroidal neovascularization membranes.
CONCLUSIONS: RPE-derived myofibroblasts via ROCK2-mediated EMT play a dominant role in SRF formation. ROCK inhibitors, particularly Ripasudil, may serve as effective therapeutic agents against fibrosis in nAMD.