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, Gou Young Koh

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70 Citations (Scopus)

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.

Original languageEnglish
Article number15296
JournalNature communications
Volume8
DOIs
Publication statusPublished - 2017 May 16

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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  • Cite this

    Park, D. Y., Lee, J., Kim, J., Kim, K., Hong, S., Han, S., Kubota, Y., Augustin, H. G., Ding, L., Kim, J. W., Kim, H., He, Y., Adams, R. H., & Koh, G. Y. (2017). Plastic roles of pericytes in the blood-retinal barrier. Nature communications, 8, [15296]. https://doi.org/10.1038/ncomms15296