{
  "abstract": "Polypoidal choroidal vasculopathy (PCV) is a distinct variant of neovascular age‐related macular degeneration (AMD) and a major cause of vision loss in older adults, yet its pathogenesis remains poorly understood. Pachychoroid PCV is a subtype characterized by poor treatment response, minimal typical AMD features, and dilated choroidal vessels. Using a multicenter PCV cohort, we conducted plasma multi‐omics analyses and identified enrichment of fluid shear stress and atherosclerosis (FSS‐AS) signaling pathways in this subtype. The pachychoroid phenotype, together with FSS‐AS enrichment, implicated altered choroidal hemodynamics in its pathogenesis. By inducing choroidal circulatory hypertension (CCH) in mice, we recapitulated, for the first time, the hallmark ocular lesions of pachychoroid PCV. Single‐cell sequencing identified the cellular origin of these angiogenic lesions and implicated endothelin‐1 (EDN1) as a key effector. Alleviating choroidal hypertension, reducing EDN1 expression, or pharmacologically blocking the endothelin receptor A (EDNRA, the receptor for EDN1), prevented lesion formation. In vitro, disturbed fluid shear stress upregulated EDN1 in choroidal endothelial cells and promoted pathological remodeling and angiogenesis through EDNRA. Collectively, our findings define a pathogenic cascade wherein CCH induces abnormal hemodynamics (disrupted fluid shear stress) and drives angiogenesis via the EDN1/EDNRA axis, offering mechanistic insight and identifying a potential therapeutic target for pachychoroid PCV.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China",
    "Beijing Key Laboratory of Fundus Diseases Intelligent Diagnosis & Drug/Device Development and Translation Beijing China",
    "Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences Beijing China",
    "Department of Ophthalmology, the First Affiliated Hospital, School of Medicine Zhejiang University Hangzhou Zhejiang China",
    "School of Pharmaceutical Sciences Capital Medical University Beijing China",
    "Beijing Area Major Laboratory of Peptide and Small Molecular Drugs Capital Medical University Beijing China",
    "Institute of Clinical Medicine National Infrastructure for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China",
    "State Key Laboratory of Common Mechanism Research of Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China",
    "Department of Ophthalmology Peking University Third Hospital Beijing China",
    "Department of Clinical Laboratory State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
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        0,
        1,
        2
      ],
      "name": "Xinyu Zhao"
    },
    {
      "affs": [
        3
      ],
      "name": "Tiantian Cheng"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Wenfei Zhang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xingwang Gu"
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    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Qing Zhao"
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    {
      "affs": [
        4,
        5
      ],
      "name": "Yaning Chen"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lihui Meng"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jiaqi Zhang"
    },
    {
      "affs": [
        6
      ],
      "name": "Bintao Qiu"
    },
    {
      "affs": [
        7
      ],
      "name": "Lili Li"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Shiyu Cheng"
    },
    {
      "affs": [
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        5
      ],
      "name": "Zicheng Wang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Chuting Wang"
    },
    {
      "affs": [
        8
      ],
      "name": "Yuelin Wang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zuyi Yang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zhengming Shi"
    },
    {
      "affs": [
        9
      ],
      "name": "Ye Guo"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Shengzhi Liu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Youxin Chen",
      "orcid": "0000-0002-7231-5058"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7vqeyc4mv1f6c.bib",
  "cited_by": 0,
  "doi": "10.1002/imt2.70176",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13625922/",
  "id": "7vqeyc4mv1f6c",
  "issns": [
    "2770-5986",
    "2770-596X"
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  "landing_url": "https://doi.org/10.1002/imt2.70176",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
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      "heading",
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      "2731|Retinal Diseases and Treatments"
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  "pdf_url": null,
  "pmcid": "PMC13625922",
  "pmid": "42819474",
  "published": "2026-09-30",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/7vqeyc4mv1f6c.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:23:33Z",
      "native_id": "PMC13625922",
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      "url": "https://doi.org/10.1002/imt2.70176"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Gut microbiota and health",
      "subfield": "molecular-biology"
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  ],
  "title": "Dissecting the angiogenic mechanism of pachychoroid polypoidal choroidal vasculopathy",
  "title_text": "Dissecting the angiogenic mechanism of pachychoroid polypoidal choroidal vasculopathy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:20:47Z",
  "url": "https://research.draconitic.com/paper/7vqeyc4mv1f6c",
  "venue": "iMeta",
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