Premium
Antiangiogenic effects of β 2 ‐adrenergic receptor blockade in a mouse model of oxygen‐induced retinopathy
Author(s) -
Martini Davide,
Monte Massimo Dal,
Ristori Chiara,
Cupisti Elena,
Mei Sara,
Fiorini Patrizio,
Filippi Luca,
Bagnoli Paola
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07530.x
Subject(s) - retinal , retinopathy of prematurity , angiogenesis , retina , neovascularization , hypoxia (environmental) , blockade , propranolol , vascular endothelial growth factor , kinase insert domain receptor , retinopathy , vascular endothelial growth factor a , endocrinology , receptor , biology , medicine , chemistry , neuroscience , ophthalmology , oxygen , vegf receptors , pregnancy , organic chemistry , genetics , diabetes mellitus , gestational age
J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07530.x Abstract Oxygen‐induced retinopathy (OIR) is a model for human retinopathy of prematurity. In mice with OIR, beta‐adrenergic receptor (β‐AR) blockade with propranolol has been shown to ameliorate different aspects of retinal dysfunction in response to hypoxia. In the present study, we used the OIR model to investigate the role of distinct β‐ARs on retinal proangiogenic factors, pathogenic neovascularization and electroretinographic responses. Our results demonstrate that β 2 ‐AR blockade with ICI 118,551 decreases retinal levels of proangiogenic factors and reduces pathogenic neovascularization, whereas β 1 ‐ and β 3 ‐AR antagonists do not. Determination of retinal protein kinase A activity is indicative of the fact that β‐AR blockers are indeed effective at the receptor level. In addition, the specificity of ICI 118,551 on retinal angiogenesis has been demonstrated by the finding that in mouse retinal explants, β 2 ‐AR silencing prevents ICI 118,551 effects on hypoxia‐induced vascular endothelial growth factor accumulation. In OIR mice, ICI 118,551 is effective in increasing electroretinographic responses suggesting that activation of β 2 ‐ARs constitutes an important part of the retinal response to hypoxia. Lastly, immunohistochemical studies demonstrate that β 2 ‐ARs are localized to several retinal cells, particularly to Müller cells suggesting the possibility that β 2 ‐ARs play a role in regulating vascular endothelial growth factor production by these cells. The present results suggest that pathogenic angiogenesis, a key change in many hypoxic/ischemic vision‐threatening retinal diseases, depends at least in part on β 2 ‐AR activity and indicate that β 2 ‐AR blockade can be effective against retinal angiogenesis.