TY - JOUR
T1 - Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy
AU - Park, Hongryeol
AU - Yamamoto, Hiroyuki
AU - Mohn, Lucas
AU - Ambühl, Lea
AU - Kanai, Kenichi
AU - Schmidt, Inga
AU - Kim, Kee Pyo
AU - Fraccaroli, Alessia
AU - Feil, Silke
AU - Junge, Harald J.
AU - Montanez, Eloi
AU - Berger, Wolfgang
AU - Adams, Ralf H.
N1 - 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).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-13220-3
DO - 10.1038/s41467-019-13220-3
M3 - Article
C2 - 31748531
AN - SCOPUS:85075346120
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5243
ER -
