Plastic roles of pericytes in the blood-retinal barrier

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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 (PDGFRb) 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/PDGFRb 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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2017-05
Language
English
Article Type
Article
Keywords

ENDOTHELIAL GROWTH-FACTOR; DIABETIC-RETINOPATHY; GENE-EXPRESSION; ACTIVATES TIE2; BRAIN-BARRIER; IN-VIVO; PDGF-B; ANGIOPOIETIN-2; ANGIOGENESIS; CELLS

Citation

NATURE COMMUNICATIONS, v.8

ISSN
2041-1723
DOI
10.1038/ncomms15296
URI
http://hdl.handle.net/10203/224092
Appears in Collection
BS-Journal Papers(저널논문)MSE-Journal Papers(저널논문)
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