VEGF is an autocrine/paracrine neuroprotective factor for injured retinal ganglion neurons.

Aged Aged, 80 and over Animals Autocrine Communication / drug effects Cell Survival / drug effects Cells, Cultured Diabetic Retinopathy / complications Female Glaucoma / drug therapy Humans Intravitreal Injections Macular Degeneration / complications Macular Edema / complications Male Mesenchymal Stem Cells / metabolism Middle Aged Paracrine Communication / drug effects Primary Cell Culture Prospective Studies Ranibizumab / administration & dosage Rats Receptors, Vascular Endothelial Growth Factor / administration & dosage Recombinant Fusion Proteins / administration & dosage Recombinant Proteins / genetics Retinal Ganglion Cells / drug effects Vascular Endothelial Growth Factor A / antagonists & inhibitors Vascular Endothelial Growth Factor B / genetics Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
24 07 2020
Historique:
received: 12 03 2019
accepted: 18 06 2020
entrez: 26 7 2020
pubmed: 28 7 2020
medline: 22 12 2020
Statut: epublish

Résumé

Vascular endothelial growth factor-A (VEGF) is the angiogenic factor promoting the pathological neovascularization in age-related macular degeneration (AMD) or diabetic macular edema (DME). Evidences have suggested a neurotrophic and neuroprotective role of VEGF, albeit in retina, cellular mechanisms underlying the VEGF neuroprotection remain elusive. Using purified adult retinal ganglion cells (RGCs) in culture, we demonstrated here that VEGF is released by RGCs themselves to promote their own survival, while VEGF neutralization by specific antibodies or traps drastically reduced the RGC survival. These results indicate an autocrine VEGF neuroprotection on RGCs. In parallel, VEGF produced by mixed retinal cells or by mesenchymal stem cells exerted a paracrine neuroprotection on RGCs. Such neuroprotective effect was obtained using the recombinant VEGF-B, suggesting the involvement of VEGF-R1 pathway in VEGF-elicited RGC survival. Finally, glaucomatous patients injected with VEGF traps (ranibizumab or aflibercept) due to either AMD or DME comorbidity, showed a significant reduction of RGC axon fiber layer thickness, consistent with the plausible reduction of the VEGF autocrine stimulation of RGCs. Our results provide evidence of the autocrine neuroprotective function of VEGF on RGCs is crucially involved to preserve injured RGCs such as in glaucomatous patients.

Identifiants

DOI: 10.1038/s41598-020-68488-z PMID: 32710087 PMC: PMC7382485
pubmed: 32710087
doi: 10.1038/s41598-020-68488-z
pii: 10.1038/s41598-020-68488-z
pmc: PMC7382485
doi:

Substances chimiques

Recombinant Fusion Proteins 0
Recombinant Proteins 0
VEGFA protein, human 0
VEGFB protein, human 0
Vascular Endothelial Growth Factor A 0
Vascular Endothelial Growth Factor B 0
vascular endothelial growth factor A, rat 0
aflibercept 15C2VL427D
FLT1 protein, human EC 2.7.10.1
Receptors, Vascular Endothelial Growth Factor EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-1 EC 2.7.10.1
Ranibizumab ZL1R02VT79

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12409

Références

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Auteurs

Nicolas Froger (N)

Sorbonne Université, INSERM, CNRS, Institut de La Vision, 17 rue Moreau, 75012, Paris, France. nifroger@yahoo.fr.

Frédéric Matonti (F)

Sorbonne Université, INSERM, CNRS, Institut de La Vision, 17 rue Moreau, 75012, Paris, France.
Centre Monticelli Paradis, 433 bis rue Paradis, 13008, Marseille, France.
Aix Marseille Univ, CNRS, INT, Inst Neurosci Timone, 13005, Marseille, France.

Christophe Roubeix (C)

Sorbonne Université, INSERM, CNRS, Institut de La Vision, 17 rue Moreau, 75012, Paris, France.

Valérie Forster (V)

Sorbonne Université, INSERM, CNRS, Institut de La Vision, 17 rue Moreau, 75012, Paris, France.

Ivana Ivkovic (I)

Sorbonne Université, INSERM, CNRS, Institut de La Vision, 17 rue Moreau, 75012, Paris, France.

Nadège Brunel (N)

UMS 29 INSERM Plateforme FluExGen UPMC, 75012, Paris, France.

Christophe Baudouin (C)

Sorbonne Université, INSERM, CNRS, Institut de La Vision, 17 rue Moreau, 75012, Paris, France.
CHNO Des Quinze-Vingts, DHU Sight Restore, INSERM-DGOS CIC 1423, 75012, Paris, France.

José-Alain Sahel (JA)

Sorbonne Université, INSERM, CNRS, Institut de La Vision, 17 rue Moreau, 75012, Paris, France.
CHNO Des Quinze-Vingts, DHU Sight Restore, INSERM-DGOS CIC 1423, 75012, Paris, France.
Fondation Ophtalmologique Adolphe de Rothschild, 75020, Paris, France.
Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.

Serge Picaud (S)

Sorbonne Université, INSERM, CNRS, Institut de La Vision, 17 rue Moreau, 75012, Paris, France. serge.picaud@inserm.fr.
Fondation Ophtalmologique Adolphe de Rothschild, 75020, Paris, France. serge.picaud@inserm.fr.
ORCID: 0000-0002-0548-5145

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Eucaryotes › Animaux › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Communication cellulaire › Communication autocrine › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Cellules › Cellules cultivées › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Complications du diabète › Angiopathies diabétiques › Rétinopathie diabétique › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Maladies de l'oeil › Hypertension oculaire › Glaucome › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Injections › Injections oculaires › Injections intravitréennes › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Dégénérescence de la rétine › Dégénérescence maculaire › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Dégénérescence de la rétine › Dégénérescence maculaire › Oedème maculaire › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches multipotentes › Cellules souches mésenchymateuses › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Communication cellulaire › Communication paracrine › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Ranibizumab › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs aux facteurs de croissance endothéliale vasculaire › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines recombinantes › Protéines de fusion recombinantes › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines recombinantes › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Cellules › Neurones › Neurones afférents › Neurones rétiniens › Cellules ganglionnaires rétiniennes › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines angiogéniques › Facteurs de croissance endothéliale vasculaire › Facteur de croissance endothéliale vasculaire de type A › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines angiogéniques › Facteurs de croissance endothéliale vasculaire › Facteur de croissance endothéliale vasculaire de type B › VEGF is an autocrine/paracrine neuroprotective...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs aux facteurs de croissance endothéliale vasculaire › Récepteur-1 au facteur croissance endothéliale vasculaire › VEGF is an autocrine/paracrine neuroprotective...