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VEGFR1 signaling in retinal angiogenesis and microinflammation.
Prog Retin Eye Res. 2021 Sep; 84:100954.PR

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), 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.

Authors+Show Affiliations

Department of Retinal Vascular Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. Electronic address: uemura@med.nagoya-cu.ac.jp.UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK. Electronic address: m.fruttiger@ucl.ac.uk.Schepens Eye Research Institute of Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA, 02114, USA. Electronic address: patricia_damore@meei.harvard.edu.Angiogenesis Laboratory, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", Via Pietro Castellino 111, 80131 Naples, Italy; ANBITION S.r.l., Via Manzoni 1, 80123, Naples, Italy. Electronic address: sandro.defalco@igb.cnr.it.Department of Ophthalmology, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, and Augustenburger Platz 1, 13353, Berlin, Germany. Electronic address: antonia.Joussen@charite.de.Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France. Electronic address: florian.sennlaub@gmail.com.Bayer Consumer Care AG, Pharmaceuticals, Peter-Merian-Strasse 84, CH-4052 Basel, Switzerland. Electronic address: lynne.brunck@bayer.com.Bayer Consumer Care AG, Pharmaceuticals, Peter-Merian-Strasse 84, CH-4052 Basel, Switzerland. Electronic address: kristian.johnson@bayer.com.Bayer Consumer Care AG, Pharmaceuticals, Peter-Merian-Strasse 84, CH-4052 Basel, Switzerland. Electronic address: george.lambrou@bayer.com.Bayer Consumer Care AG, Pharmaceuticals, Peter-Merian-Strasse 84, CH-4052 Basel, Switzerland. Electronic address: kay.rittenhouse@bayer.com.Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 9, 50931, Cologne, Germany. Electronic address: thomas.langmann@uk-koeln.de.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

33640465

Citation

Uemura, Akiyoshi, et al. "VEGFR1 Signaling in Retinal Angiogenesis and Microinflammation." Progress in Retinal and Eye Research, vol. 84, 2021, p. 100954.
Uemura A, Fruttiger M, D'Amore PA, et al. VEGFR1 signaling in retinal angiogenesis and microinflammation. Prog Retin Eye Res. 2021;84:100954.
Uemura, A., Fruttiger, M., D'Amore, P. A., De Falco, S., Joussen, A. M., Sennlaub, F., Brunck, L. R., Johnson, K. T., Lambrou, G. N., Rittenhouse, K. D., & Langmann, T. (2021). VEGFR1 signaling in retinal angiogenesis and microinflammation. Progress in Retinal and Eye Research, 84, 100954. https://doi.org/10.1016/j.preteyeres.2021.100954
Uemura A, et al. VEGFR1 Signaling in Retinal Angiogenesis and Microinflammation. Prog Retin Eye Res. 2021;84:100954. PubMed PMID: 33640465.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - VEGFR1 signaling in retinal angiogenesis and microinflammation. AU - Uemura,Akiyoshi, AU - Fruttiger,Marcus, AU - D'Amore,Patricia A, AU - De Falco,Sandro, AU - Joussen,Antonia M, AU - Sennlaub,Florian, AU - Brunck,Lynne R, AU - Johnson,Kristian T, AU - Lambrou,George N, AU - Rittenhouse,Kay D, AU - Langmann,Thomas, Y1 - 2021/02/25/ PY - 2020/07/17/received PY - 2021/02/12/revised PY - 2021/02/19/accepted PY - 2022/08/25/pmc-release PY - 2021/3/1/pubmed PY - 2021/3/1/medline PY - 2021/2/28/entrez KW - Angiogenesis KW - Microinflammation KW - Placental growth factor (PlGF) KW - Vascular endothelial growth factor receptor 1 (VEGFR1) KW - Vascular endothelial growth factor-A (VEGF-A) SP - 100954 EP - 100954 JF - Progress in retinal and eye research JO - Prog Retin Eye Res VL - 84 N2 - 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), 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. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/33640465/VEGFR1_signaling_in_retinal_angiogenesis_and_microinflammation. L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(21)00015-X DB - PRIME DP - Unbound Medicine ER -
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