Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy.
Hongryeol ParkHiroyuki YamamotoLucas MohnLea AmbühlKenichi KanaiInga SchmidtKee-Pyo KimAlessia FraccaroliSilke FeilHarald J JungeEloi MontanezWolfgang BergerRalf H AdamsPublished in: Nature communications (2019)
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.
Keyphrases
- endothelial cells
- diabetic retinopathy
- optical coherence tomography
- optic nerve
- genome wide
- copy number
- high glucose
- vascular endothelial growth factor
- age related macular degeneration
- end stage renal disease
- single cell
- ejection fraction
- cell proliferation
- cell therapy
- genome wide identification
- newly diagnosed
- single molecule
- preterm infants
- chronic kidney disease
- dna methylation
- mouse model
- peritoneal dialysis
- protein kinase
- electronic health record
- prognostic factors
- risk factors
- cell free
- gene expression
- big data
- artificial intelligence
- induced pluripotent stem cells
- patient reported
- patient reported outcomes
- deep learning
- machine learning