Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity

Hoffmann, J; Feng, Y; vom Hagen, F; Hillenbrand, A; Lin, J; Erber, R; Vajkoczy, P; Gourzoulidou, E; Waldmann, H; Giannis, A; Wolburg, H; Shani, M; Jaeger, V; Weich, HA; Preissner, KT; Hoffmann, S; Deutsch, U; Hammes, HP (2005). Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity. FASEB journal, 14(19), pp. 2035-6. Bethesda, Md.: Federation of American Societies for Experimental Biology 10.1096/fj.04-2109fje

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Pericyte loss and capillary regression are characteristic for incipient diabetic retinopathy. Pericyte recruitment is involved in vessel maturation, and ligand-receptor systems contributing to pericyte recruitment are survival factors for endothelial cells in pericyte-free in vitro systems. We studied pericyte recruitment in relation to the susceptibility toward hyperoxia-induced vascular remodeling using the pericyte reporter X-LacZ mouse and the mouse model of retinopathy of prematurity (ROP). Pericytes were found in close proximity to vessels, both during formation of the superficial and the deep capillary layers. When exposure of mice to the ROP was delayed by 24 h, i.e., after the deep retinal layer had formed [at postnatal (p) day 8], preretinal neovascularizations were substantially diminished at p18. Mice with a delayed ROP exposure had 50% reduced avascular zones. Formation of the deep capillary layers at p8 was associated with a combined up-regulation of angiopoietin-1 and PDGF-B, while VEGF was almost unchanged during the transition from a susceptible to a resistant capillary network. Inhibition of Tie-2 function either by soluble Tie-2 or by a sulindac analog, an inhibitor of Tie-2 phosphorylation, resensitized retinal vessels to neovascularizations due to a reduction of the deep capillary network. Inhibition of Tie-2 function had no effect on pericyte recruitment. Our data indicate that the final maturation of the retinal vasculature and its resistance to regressive signals such as hyperoxia depend on the completion of the multilayer structure, in particular the deep capillary layers, and are independent of the coverage by pericytes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Deutsch, Urban

ISSN:

0892-6638

ISBN:

16215210

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

04 May 2014 23:15

Publisher DOI:

10.1096/fj.04-2109fje

PubMed ID:

16215210

Web of Science ID:

000232991100024

URI:

https://boris.unibe.ch/id/eprint/22212 (FactScience: 32278)

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