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Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy

Author

Listed:
  • Hongryeol Park

    (University of Münster, Faculty of Medicine)

  • Hiroyuki Yamamoto

    (University of Münster, Faculty of Medicine
    Narita-Tomisato Tokushukai Hospital)

  • Lucas Mohn

    (University of Zurich
    University of Zurich)

  • Lea Ambühl

    (University of Zurich)

  • Kenichi Kanai

    (University of Münster, Faculty of Medicine)

  • Inga Schmidt

    (University of Münster, Faculty of Medicine)

  • Kee-Pyo Kim

    (Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology)

  • Alessia Fraccaroli

    (University Hospital, LMU Munich
    University Hospital, LMU Munich)

  • Silke Feil

    (University of Zurich)

  • Harald J. Junge

    (University of Colorado
    University of Minnesota Medical School)

  • Eloi Montanez

    (University Hospital, LMU Munich
    University of Barcelona and Bellvitge Biomedical Research Institute (IDIBELL))

  • Wolfgang Berger

    (University of Zurich
    University of Zurich
    University and ETH Zurich)

  • Ralf H. Adams

    (University of Münster, Faculty of Medicine)

Abstract

Familial exudative vitreoretinopathy (FEVR) is a human disease characterized by defective retinal angiogenesis and associated complications that can result in vision loss. Defective Wnt/β-catenin signaling is an established cause of FEVR, whereas other molecular alterations contributing to the disease remain insufficiently understood. Here, we show that integrin-linked kinase (ILK), a mediator of cell-matrix interactions, is indispensable for retinal angiogenesis. Inactivation of the murine Ilk gene in postnatal endothelial cells results in sprouting defects, reduced endothelial proliferation and disruption of the blood-retina barrier, resembling phenotypes seen in established mouse models of FEVR. Retinal vascularization defects are phenocopied by inducible inactivation of the gene for α-parvin (Parva), an interactor of ILK. Screening genomic DNA samples from exudative vitreoretinopathy patients identifies three distinct mutations in human ILK, which compromise the function of the gene product in vitro. Together, our data suggest that defective cell-matrix interactions are linked to Wnt signaling and FEVR.

Suggested Citation

  • Hongryeol Park & Hiroyuki Yamamoto & Lucas Mohn & Lea Ambühl & Kenichi Kanai & Inga Schmidt & Kee-Pyo Kim & Alessia Fraccaroli & Silke Feil & Harald J. Junge & Eloi Montanez & Wolfgang Berger & Ralf H, 2019. "Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13220-3
    DOI: 10.1038/s41467-019-13220-3
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    Cited by:

    1. Haifeng Zhang & Busu Li & Qunhua Huang & Francesc López-Giráldez & Yoshiaki Tanaka & Qun Lin & Sameet Mehta & Guilin Wang & Morven Graham & Xinran Liu & In-Hyun Park & Anne Eichmann & Wang Min & Jenny, 2022. "Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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