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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2018 (publ. 2017, arch)     Display Documents

ID: 744128.0, MPI für molekulare Biomedizin / Jahrbuch 2018 (publ. 2017, arch)
Reversible retinal vessel closure from VEGF-induced leukocyte plugging
Authors:Liu, Y.; Shen, J.; Fortmann, S. D.; Wang, J.; Vestweber, D.; Campochiaro, P. A.
Date of Publication (YYYY-MM-DD):2017-09-21
Title of Journal:Jci Insight
Issue / Number:18
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Clinical trials in patients with macular edema due to diabetic retinopathy or retinal vein occlusion (RVO) have shown that suppression of VEGF not only improves macular edema, but also reopens closed retinal vessels, prevents progression of vessel closure, and improves retinopathy. In this study, we show the molecular basis for those clinical observations. Increased retinal levels of VEGF in mice cause plugging of retinal vessels with leukocytes, vessel closure, and hypoxia. Suppression of VEGF reduces leukocyte plugging, causing reperfusion of closed vessels. Activation of VEGFR1 contributes to leukocyte recruitment, because it is significantly reduced by an anti-VEGFR1-neutralizing antibody. High VEGF increases transcriptional activity of NF-kappaB and expression of NF-kappaB target genes, particularly Vcam1. Injection of an anti-VCAM-1-neutralizing antibody reduces VEGF-induced leukocyte plugging. These data explain the broad range of benefits obtained by VEGF suppression in patients with ischemic retinopathies, provide an important insight into the pathogenesis of RVO and diabetic retinopathy, and suggest that sustained suppression of VEGF early in the course of these diseases may prevent vessel closure, worsening ischemia, and disease progression. This study also identifies VEGFR1 and VCAM-1 as molecular targets whose suppression could supplement VEGF neutralization for treatment of RVO and diabetic retinopathy.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:MPI für molekulare Biomedizin
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Johns Hopkins Biostatistics Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. Department of Cell Biology, Max-Planck-Institute of Molecular Biomedicine, Muenster, Germany.
Identifiers:ISSN:2379-3708 (Electronic) 2379-3708 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/28931763 [ID No:2]
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