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

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 () and Ralf H. Adams ()
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Hongryeol Park: University of Münster, Faculty of Medicine
Hiroyuki Yamamoto: University of Münster, Faculty of Medicine
Lucas Mohn: 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
Silke Feil: University of Zurich
Harald J. Junge: University of Colorado
Eloi Montanez: University Hospital, LMU Munich
Wolfgang Berger: University of Zurich
Ralf H. Adams: University of Münster, Faculty of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13220-3

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