Nerve growth factor regulates endothelial cell survival and pathological retinal angiogenesis.
Antibodies, Neutralizing
/ pharmacology
Apoptosis
/ drug effects
Endothelial Cells
Humans
Injections, Intraocular
Membrane Potential, Mitochondrial
/ drug effects
Neovascularization, Pathologic
/ genetics
Nerve Growth Factor
/ antagonists & inhibitors
Neurons
/ drug effects
Proto-Oncogene Proteins c-bcl-2
/ genetics
Retina
/ drug effects
Retinopathy of Prematurity
/ genetics
bcl-2-Associated X Protein
/ genetics
NGF
angiogenesis
apoptosis
endothelium
hypoxia
mitochondria
retinopathy
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
29
03
2018
revised:
28
09
2018
accepted:
15
10
2018
pubmed:
27
1
2019
medline:
11
7
2020
entrez:
26
1
2019
Statut:
ppublish
Résumé
The mechanism underlying vasoproliferative retinopathies like retinopathy of prematurity (ROP) is hypoxia-triggered neovascularisation. Nerve growth factor (NGF), a neurotrophin supporting survival and differentiation of neuronal cells may also regulate endothelial cell functions. Here we studied the role of NGF in pathological retinal angiogenesis in the course of the ROP mouse model. Topical application of NGF enhanced while intraocular injections of anti-NGF neutralizing antibody reduced pathological retinal vascularization in mice subjected to the ROP model. The pro-angiogenic effect of NGF in the retina was mediated by inhibition of retinal endothelial cell apoptosis. In vitro, NGF decreased the intrinsic (mitochondria-dependent) apoptosis in hypoxia-treated human retinal microvascular endothelial cells and preserved the mitochondrial membrane potential. The anti-apoptotic effect of NGF was associated with increased BCL2 and reduced BAX, as well as with enhanced ERK and AKT phosphorylation, and was abolished by inhibition of the AKT pathway. Our findings reveal an anti-apoptotic role of NGF in the hypoxic retinal endothelium, which is involved in promoting pathological retinal vascularization, thereby pointing to NGF as a potential target for proliferative retinopathies.
Identifiants
pubmed: 30680928
doi: 10.1111/jcmm.14002
pmc: PMC6433692
doi:
Substances chimiques
Antibodies, Neutralizing
0
BCL2 protein, human
0
Proto-Oncogene Proteins c-bcl-2
0
bcl-2-Associated X Protein
0
Nerve Growth Factor
9061-61-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2362-2371Informations de copyright
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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