Uemura, A;
Fruttiger, M;
D'Amore, PA;
De Falco, S;
Joussen, AM;
Sennlaub, F;
Brunck, LR;
... Langmann, T; + view all
(2021)
VEGFR1 signaling in retinal angiogenesis and microinflammation.
Progress in Retinal and Eye Research
, Article 100954. 10.1016/j.preteyeres.2021.100954.
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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 to 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), Müller 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.
| Type: | Article |
|---|---|
| Title: | VEGFR1 signaling in retinal angiogenesis and microinflammation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.preteyeres.2021.100954 |
| Publisher version: | http://dx.doi.org/10.1016/j.preteyeres.2021.100954 |
| Language: | English |
| Additional information: | This article is published under a creative commons license (https://creativecommons.org/licenses/by/4.0/) |
| Keywords: | Angiogenesis, Microinflammation, Placental growth factor (PlGF), Vascular endothelial growth factor-A (VEGF-A), Vascular endothelial growth factor receptor 1 (VEGFR1) |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10123063 |
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