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Angiogenesis
Published in: Angiogenesis 2/2018

Open Access 01-05-2018 | Original Paper

Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization

Authors: Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Pierfrancesco Mirabelli, Mieszko Lachota, Lasse Jensen, Beatrice Peebo, Neil Lagali

Published in: Angiogenesis | Issue 2/2018

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Abstract

Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.
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Metadata
Title
Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization
Authors
Anthony Mukwaya
Anton Lennikov
Maria Xeroudaki
Pierfrancesco Mirabelli
Mieszko Lachota
Lasse Jensen
Beatrice Peebo
Neil Lagali
Publication date
01-05-2018
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 2/2018
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-018-9604-y

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