Nerve growth factor regulates endothelial cell survival and pathological retinal angiogenesis.
Maria TroullinakiVasileia Ismini AlexakiIoannis MitroulisAnke WittAnne Klotzsche-von AmelnKyoung-Jin ChungTriantafyllos ChavakisMatina EconomopoulouPublished in: Journal of cellular and molecular medicine (2019)
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.
Keyphrases
- growth factor
- endothelial cells
- diabetic retinopathy
- optical coherence tomography
- optic nerve
- high glucose
- cell death
- cell proliferation
- signaling pathway
- vascular endothelial growth factor
- oxidative stress
- mouse model
- cell cycle arrest
- induced apoptosis
- endoplasmic reticulum stress
- dna methylation
- adipose tissue
- anti inflammatory
- gene expression
- type diabetes
- brain injury
- climate change
- wound healing
- cerebral ischemia
- ultrasound guided
- newly diagnosed
- peripheral nerve
- skeletal muscle
- endoplasmic reticulum