Plastic roles of pericytes in the blood-retinal barrier.

Details

Serval ID
serval:BIB_D076AF5F9971
Type
Article: article from journal or magazin.
Collection
Publications
Title
Plastic roles of pericytes in the blood-retinal barrier.
Journal
Nature communications
Author(s)
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.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
16/05/2017
Peer-reviewed
Oui
Volume
8
Pages
15296
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
10/03/2022 8:54
Last modification date
11/03/2022 6:33
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