VEGF inhibition alters neurotrophin signalling pathways and induces caspase-3 activation and autophagy in rabbit retina.

Abstract:

:This study sought to evaluate the prospective role exerted by vascular endothelial growth factor (VEGF) in the modulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) signalling pathways in the rabbit retina. To reach this aim, the anti-VEGF agents aflibercept and ranibizumab were used as a pharmacological approach to evaluate the putative consequences elicited by VEGF inhibition on neurotrophin signalling. VEGF inhibition determined a marked imbalance in proneurotrophin expression, a significant reduction in TrkA and TrkB phosphorylation states and a decrease in the pan-neurotrophin receptor p75. Importantly, VEGF blockade also caused a strong increase in cleaved caspase-3, beclin-1 and lipidated LC3. The effects were more pronounced in the aflibercept group when compared with ranibizumab-treated rabbits, particularly 1 week after injection. This study demonstrates that VEGF exerts pivotal physiological roles in regulating NGF and BDNF pathways in the retina, as its inhibition by anti-VEGF agents deeply impacts neurotrophin homeostasis. These events are accompanied by a sustained induction of apoptotic and autophagic markers, suggesting that anti-VEGF-dependent impairments in neurotrophin signalling could be responsible for the activation of retinal cell death pathways.

journal_name

J Cell Physiol

authors

Segatto M,Fico E,Gharbiya M,Rosso P,Carito V,Tirassa P,Plateroti R,Lambiase A

doi

10.1002/jcp.28462

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

18297-18307

issue

10

eissn

0021-9541

issn

1097-4652

journal_volume

234

pub_type

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