Open AccessNerve growth factor regulates endothelial cell survival and pathological retinal angiogenesis
Author(s) -
Troullinaki Maria,
Alexaki VasileiaIsmini,
Mitroulis Ioannis,
Witt Anke,
Klotzsche–von Ameln Anne,
Chung KyoungJin,
Chavakis Triantafyllos,
Economopoulou Matina
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14002
Subject(s) - nerve growth factor , angiogenesis , retinal , retina , vascular endothelial growth factor , apoptosis , biology , protein kinase b , neurotrophin , microbiology and biotechnology , vascular endothelial growth factor a , endothelial stem cell , cancer research , endocrinology , phosphorylation , neuroscience , in vitro , receptor , biochemistry , vegf receptors
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 BCL 2 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.