Plastic roles of pericytes in the blood-retinal barrier

Nat Commun. 2017 May 16;8:15296. doi: 10.1038/ncomms15296.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-2 / metabolism
  • Animals
  • Blood-Retinal Barrier / metabolism*
  • Capillary Permeability / genetics
  • Diabetic Retinopathy / genetics
  • Diabetic Retinopathy / metabolism*
  • Endothelial Cells / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Pericytes / metabolism*
  • Proto-Oncogene Proteins c-sis / genetics
  • Proto-Oncogene Proteins c-sis / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Retinal Vessels / metabolism*
  • Signal Transduction / genetics

Substances

  • Angiopoietin-2
  • Proto-Oncogene Proteins c-sis
  • Receptor, Platelet-Derived Growth Factor beta