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, Ralf H. Adams

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number5243
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Funding Information:
Funding was provided by the Max–Planck-Society, the University of Münster and the German Research Foundation (SFB 1009, SFB 1366, cluster of excellence “Cells in Motion” and project number 391580220). E.M. and A.F. were also supported by the German Research Foundation (MO2562/1–2) and H.J.J. by the NIH (R01 EY024261).

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