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Plastic roles of pericytes in the blood–retinal barrier

Author

Listed:
  • 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)
    Center for Vascular Research, Institute of Basic Science (IBS))

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.

Suggested Citation

  • 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 & Gou You, 2017. "Plastic roles of pericytes in the blood–retinal barrier," Nature Communications, Nature, vol. 8(1), pages 1-16, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15296
    DOI: 10.1038/ncomms15296
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    Cited by:

    1. Thomas L. Maurissen & Alena J. Spielmann & Gabriella Schellenberg & Marc Bickle & Jose Ricardo Vieira & Si Ying Lai & Georgios Pavlou & Sascha Fauser & Peter D. Westenskow & Roger D. Kamm & Héloïse Ra, 2024. "Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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