{
  "abstract": "Background\n\nCellular senescence plays a key role in the pathogenesis of neovascular age-related macular degeneration (nAMD). Senomorphic therapy, which targets the senescence-associated secretory phenotype (SASP), holds promise for treating age-related diseases; however, effective senomorphic treatments for nAMD remain lacking.Methods\n\nWe screened a panel of senomorphic agents in bleomycin- and ionizing radiation (IR)-induced senescent ARPE-19 cells to identify a lead compound for nAMD. Bulk and single-cell RNA sequencing data were analyzed to explore JAK-STAT signaling activation. Ruxolitinib and siRNA were used to validate the role of the JAK1/2-STAT3 pathway in senescent retinal pigment epithelium (RPE). A laser-induced choroidal neovascularization (CNV) model was established in Brown-Norway rats for in vivo studies.Results\n\nRuxolitinib, a JAK1/2 inhibitor, most effectively suppressed SASP factors and complement C3 expression while restoring pigment epithelium-derived factor (PEDF) levels in senescent ARPE-19 cells. Knockdown of JAK1 or JAK2 significantly reversed the expression of vascular endothelial growth factor (VEGF), C3, and PEDF. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) revealed activation of the JAK-STAT pathway in nAMD patient samples, CNV models, and senescent RPE cells, which was corroborated in the CNV rat model. Inhibition of JAK1/2-STAT3 with ruxolitinib markedly reduced vascular leakage and CNV area, and accelerated recovery of retinal function. The combination of ruxolitinib with anti-VEGF therapy presented a better effect on inhibiting CNV area. Furthermore, intravitreal injection of ruxolitinib showed no significant structural or functional toxicity in normal rat retinas over one month.Conclusions\n\nOur study identifies the JAK1/2-STAT3 pathway as a key regulator of the SASP in senescent RPE and confirms its activation in nAMD and experimental CNV. Pharmacologic inhibition of this pathway with ruxolitinib effectively attenuates CNV progression with a favorable short-term safety profile, supporting its potential as a senomorphic therapy for nAMD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.",
    "Key Laboratory of Gastrointestinal Cancer, Fujian Medical University, Ministry of Education, Fuzhou, China.",
    "Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.",
    "Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing, 100083, China.",
    "Department of Ophthalmology, Peking University Third Hospital, Beijing, China.",
    "Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan, Shandong, China.",
    "Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.",
    "Zhejiang Hailiang Biotechnology Co., Ltd, Hangzhou, Zhejiang, China.",
    "Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing, 100083, China. zbmao@bjmu.edu.cn.",
    "Department of Ophthalmology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. 1189002@zju.edu.cn.",
    "Department of Ophthalmology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. yansheng326@zju.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yinhao Wang"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Zhihua Huang"
    },
    {
      "affs": [
        4
      ],
      "name": "Yulin Tseng"
    },
    {
      "affs": [
        0
      ],
      "name": "Huiling Ma"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Kuangqi Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinlei Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Ye"
    },
    {
      "affs": [
        0
      ],
      "name": "Tiantian Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiayun Ge"
    },
    {
      "affs": [
        7
      ],
      "name": "Jingcheng Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinglin Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianhua Xia"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianqin Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Chixin Du"
    },
    {
      "affs": [
        7
      ],
      "name": "Wei Lei"
    },
    {
      "affs": [
        8
      ],
      "name": "Zebin Mao"
    },
    {
      "affs": [
        9
      ],
      "name": "Hongguang Cui"
    },
    {
      "affs": [
        10
      ],
      "name": "Yan Sheng",
      "orcid": "0009-0004-6278-1268"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1whmr3hedy87r.bib",
  "cited_by": 0,
  "doi": "10.1186/s12967-026-08705-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13700398",
  "id": "1whmr3hedy87r",
  "issns": [
    "1479-5876"
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  "landing_url": "https://europepmc.org/article/MED/42928338",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R"
    ],
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      "openalex",
      "2731|Retinal Diseases and Treatments"
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  "pdf_url": "https://europepmc.org/articles/PMC13700398?pdf=render",
  "pmcid": "PMC13700398",
  "pmid": "42928338",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/1whmr3hedy87r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:20Z",
      "native_id": "MED:42928338",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928338"
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    {
      "first_seen": "2026-11-01T14:21:23Z",
      "native_id": "064e12fcd40844ada1d587b5c2dcd1a4",
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      "url": "https://doi.org/10.1186/s12967-026-08705-x"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2731|Retinal Diseases and Treatments",
      "subfield": "general"
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  ],
  "title": "The potential of ruxolitinib as a senomorphic therapy in alleviating neovascular age-related macular degeneration : Ruxolitinib inhibits CNV.",
  "title_text": "The potential of ruxolitinib as a senomorphic therapy in alleviating neovascular age-related macular degeneration : Ruxolitinib inhibits CNV.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T14:20:50Z",
  "url": "https://research.draconitic.com/paper/1whmr3hedy87r",
  "venue": "Journal of translational medicine",
  "versions": []
}