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Plastic roles of pericytes in the blood-retinal barrier Highly Cited Paper

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Title
Plastic roles of pericytes in the blood-retinal barrier
Author(s)
Park D.Y.; Lee J.; Kim J.; Kangsan Kim; Hong S.; Sangyeul Han; Kubota Y.; Augustin H.G.; Ding L.; Kim J.W.; Kim H.; He Y.; Adams R.H.; Gou Young Koh
Publication Date
2017-05
Journal
NATURE COMMUNICATIONS, v.8, no., pp.15296 -
Publisher
NATURE PUBLISHING GROUP
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. © 2017 The Author(s)
URI
http://pr.ibs.re.kr/handle/8788114/3623
DOI
10.1038/ncomms15296
ISSN
2041-1723
Appears in Collections:
Center for Cardiovascular Research(혈관 연구단) > Journal Papers (저널논문)
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