Universität zu Köln

Uemura, Akiyoshi ORCID: 0000-0001-5574-5470, Fruttiger, Marcus ORCID: 0000-0002-6962-5485, D'Amore, Patricia A., De Falco, Sandro ORCID: 0000-0002-6501-1697, Joussen, Antonia M., Sennlaub, Florian, Brunck, Lynne R., Johnson, Kristian T., Lambrou, George N., Rittenhouse, Kay D. and Langmann, Thomas (2021). VEGFR1 signaling in retinal angiogenesis and microinflammation. Prog. Retin. Eye Res., 84. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 1873-1635

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Abstract

Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, -C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Muller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Uemura, Akiyoshi UNSPECIFIED orcid.org/0000-0001-5574-5470 UNSPECIFIED Fruttiger, Marcus UNSPECIFIED orcid.org/0000-0002-6962-5485 UNSPECIFIED D'Amore, Patricia A. UNSPECIFIED UNSPECIFIED UNSPECIFIED De Falco, Sandro UNSPECIFIED orcid.org/0000-0002-6501-1697 UNSPECIFIED Joussen, Antonia M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sennlaub, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunck, Lynne R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Johnson, Kristian T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lambrou, George N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rittenhouse, Kay D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-602447
DOI:	10.1016/j.preteyeres.2021.100954
Journal or Publication Title:	Prog. Retin. Eye Res.
Volume:	84
Date:	2021
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication:	OXFORD
ISSN:	1873-1635
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; DIABETIC MACULAR EDEMA; VASCULAR-PERMEABILITY FACTOR; NITRIC-OXIDE SYNTHASE; SINGLE INTRAVITREAL INJECTION; OXYGEN-INDUCED RETINOPATHY; MESSENGER-RNA STABILITY; BRANCH VEIN OCCLUSION; HIGH-AFFINITY BINDING; AQUEOUS-HUMOR LEVELS Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60244