Evidence map›Paper›PMID 42132459›Full record

ArticleInvestigative ophthalmology & visual science2026

RPE With ROCK-Mediated Epithelial-Mesenchymal Transition as a Key Contributor of Subretinal Fibrosis in AMD.

Iori Wada, Keijiro Ishikawa, Muneo Yamaguchi, Shotaro Shimokawa, Ji Rui, Kenichiro Mori, Yoshihiro Kaizu, Mitsuru Arima, Shoji Notomi, Yusuke Murakami and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Iori WadaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Keijiro IshikawaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Muneo YamaguchiDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shotaro ShimokawaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ji RuiDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kenichiro MoriDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshihiro KaizuDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mitsuru ArimaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shoji NotomiDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yusuke MurakamiDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shigenori InagakiGraduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yuta KohroDepartment of Life Innovation, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Makoto TsudaDepartment of Life Innovation, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kensuke ShibataDepartment of Microbiology and Immunology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
Ryo TeraoJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Takeshi TerabayashiDepartment of Pharmacology, Oita University, Faculty of Medicine, Yufu, Japan.
Toshimasa IshizakiDepartment of Pharmacology, Oita University, Faculty of Medicine, Yufu, Japan.
Shigeo YoshidaDepartment of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.
Tatsuro IshibashiDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Susumu IshidaLaboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Rajendra S ApteJohn F. Hardesty, MD Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Koh-Hei SonodaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shintaro NakaoDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Epithelial-Mesenchymal TransitionMacular DegenerationRetinal Pigment Epitheliumrho-Associated KinasesAnimalsCells, CulturedDisease Models, AnimalFemaleFibrosisGene Expression RegulationHumansImmunohistochemistryIsoquinolinesMaleMiceMice, Inbred C57BLIsoquinolinesK-115rho-Associated KinasesROCK2 protein, humanSulfonamides

Identifiers

PMID42132459
PMCPMC13189205

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.