Plastic roles of pericytes in the blood–retinal barrier

Do Young Park, Junyeop Lee, Jaeryung Kim, Kangsan Kim, Seonpyo Hong, Sangyeul Han, Yoshiaki Kubota, Hellmut G. Augustin, Lei Ding, Jin Woo Kim, Hail Kim, Yulong He, Ralf H. Adams and Gou Young Koh ()
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Do Young Park: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Junyeop Lee: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Jaeryung Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Kangsan Kim: Center for Vascular Research, Institute of Basic Science (IBS)
Seonpyo Hong: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Sangyeul Han: Center for Vascular Research, Institute of Basic Science (IBS)
Yoshiaki Kubota: The Laboratory of Vascular Biology, Keio University
Hellmut G. Augustin: German Cancer Research Center, DKFZ-ZMBH Alliance
Lei Ding: Columbia Stem Cell Initiative, Columbia University Medical Center
Jin Woo Kim: KAIST
Hail Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Yulong He: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University
Ralf H. Adams: Max-Planck-Institute for Molecular Biomedicine, and Faculty of Medicine, University of Münster
Gou Young Koh: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: Abstract The blood–retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption. However, PDGF-B/PDGFRβ signalling is expendable for maintaining BRB integrity in adult mice. Although selective pericyte loss in stable adult retinal vessels surprisingly does not cause BRB disintegration, it sensitizes retinal vascular endothelial cells (ECs) to VEGF-A, leading to upregulation of angiopoietin-2 (Ang2) in ECs through FOXO1 activation and triggering a positive feedback that resembles the pathogenesis of DR. Accordingly, either blocking Ang2 or activating Tie2 greatly attenuates BRB breakdown, suggesting potential therapeutic approaches to reduce retinal damages upon DR progression.

Date: 2017
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DOI: 10.1038/ncomms15296

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