{
  "abstract": "AIM: To investigate whether hypoxia-activated microglia drive pathological neovascularization through extracellular matrix (ECM) remodeling and endothelial integrin signaling, a mechanism that may function in parallel with vascular endothelial growth factor (VEGF) signaling. METHODS: The oxygen-induced retinopathy (OIR) mouse model was used. Retinal phenotypes were assessed by flat mounts, histology, and vascular leakage assays. Key pathways were screened by transcriptomics and validated via Western blot, immunofluorescence, and quantitative polymerase chain reaction (qPCR). In vitro, brain microvascular endothelial cells were treated with conditioned medium from hypoxic microglia (Hyp-CM), with cell migration and tube formation assessed. Interventions employed the integrin β3 (ITGB3) inhibitor cilengitide, the focal adhesion kinase (FAK) inhibitor PF-573228 and a neutralizing anti-VEGF antibody. In vivo, cilengitide was administered by intravitreal injection to evaluate its therapeutic effect on neovascularization. RESULTS: OIR retinas showed significant avascularity, pathological neovascularization, and barrier disruption. Transcriptomics revealed activation of ECM-receptor interaction and focal adhesion pathways, with upregulation of Fn1 and Itgb3. Increased protein levels of fibronectin (FN) and ITGB3, alongside elevated phosphorylation of FAK and protein kinase B (Akt), were confirmed in vivo. Activated microglia co-localized with upregulated FN and ITGB3. Conditioned medium from Hyp-CM activated the ITGB3–FAK–Akt pathway in endothelial cells and promoted their migration and tube formation. These effects were nearly abolished by cilengitide or PF-573228. VEGF neutralization partially reduced Hyp-CM-induced migration and tube formation. Intravitreal injection of cilengitide significantly reduced retinal neovascularization in OIR mice. CONCLUSION: Hypoxia-activated microglia promote pathological angiogenesis, and the FN/ITGB3/FAK/Akt axis is identified as a key mediator of this process, revealing a novel mechanism that operates in parallel with VEGF signaling. Targeting this “hypoxia–microglia–ECM–integrin” axis represents a promising therapeutic strategy to overcome anti-VEGF resistance in ischemic retinopathy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China",
    "Beijing Collaborative Innovation Centre for Cardiovascular Disorders, the Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China",
    "Department of Vascular Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China",
    "Department of Ophthalmology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China",
    "Xiamen Eye Center and Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Lan-Cao Hao"
    },
    {
      "affs": [
        1
      ],
      "name": "De-Hui Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Kun Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Chen-Zi Liu"
    },
    {
      "affs": [
        4
      ],
      "name": "Ming-Hao Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Xin-Xiao Gao"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Si-Quan Zhu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ag268rbv2zd5c.bib",
  "cited_by": 0,
  "doi": "10.18240/ijo.2026.11.02",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13717359/",
  "id": "ag268rbv2zd5c",
  "issns": [
    "2222-3959",
    "2227-4898"
  ],
  "landing_url": "https://doi.org/10.18240/ijo.2026.11.02",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Basic Research"
    ],
    [
      "openalex",
      "1312|Angiogenesis and VEGF in Cancer"
    ]
  ],
  "openalex": "W7223018329",
  "pdf_url": "https://gjyk.ijournals.cn//gjyken/article/pdf/20261102",
  "pmcid": "PMC13717359",
  "pmid": "42959614",
  "published": "2026-11-02",
  "publisher": "Press of International Journal of Ophthalmology",
  "ris": "https://research.draconitic.com/paper/ag268rbv2zd5c.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:21:41Z",
      "native_id": "PMC13717359",
      "source": "pmc",
      "url": "https://doi.org/10.18240/ijo.2026.11.02"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Angiogenesis and VEGF in Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Hypoxia-activated microglia promote pathological angiogenesis via an FN/ITGB3/FAK/Akt pathway",
  "title_text": "Hypoxia-activated microglia promote pathological angiogenesis via an FN/ITGB3/FAK/Akt pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:41Z",
  "url": "https://research.draconitic.com/paper/ag268rbv2zd5c",
  "venue": "International Journal of Ophthalmology",
  "versions": []
}