Purpose. β-adrenergic receptors (β-ARs) regulate angiogenesis in proliferative retinopathies. We studied the effects of β1/2-AR deletion in a model of oxygen-induced retinopathy (OIR) to confirm the role of β1- and/or β2-ARs in regulating angiogenesis and to get insights into the role of β3-ARs. Methods. Mice with β1/2-AR deletion (KO) were used. Levels of norepinephrine (NE), β3-ARs, transcription and proangiogenic factors were evaluated. Retinas were analyzed for avascular area and neovascular tufts in the superficial plexus. Deep plexus and blood-retinal barrier (BRB) were also analyzed. Neovascularization, proangiogenic factors, protein kinase A (PKA) activity and nitrite production were assessed after BRL 37344, a β3-AR agonist. Results. OIR was characterized by NE up-regulation with higher levels in WT than in KO. WT and KO displayed comparable levels of β3-ARs, transcription and proangiogenic factors, but differed in vascular endothelial growth factor (VEGF) receptor (VEGFR) expression with VEGFR-1 in WT lower than in KO and VEGFR-2 in WT higher than in KO. BRB dysfunction did not differ between WT and KO. Vascular abnormalities in the superficial plexus were abolished by β1/2-AR deletion, which also helped the development of the deep plexus. In both WT and KO, β3-AR agonism, acting through the nitric oxide pathway, caused enhanced neovascular responses with increased levels of VEGF. Conclusions. We confirm that β1- and β2-ARs play a pivotal role in retinal angiogenesis. In their presence, β3-ARs potentiate angiogenic responses, whereas, in their absence, β3-ARs sustain the angiogenic drive. These results suggest β-ARs as promising targets for therapies aimed to counteract proliferative retinopathies.
|Autori:||Dal Monte M; Cammalleri M; Mattei E; Filippi L; Bagnoli P|
|Titolo:||Protective effects of beta1/2 adrenergic receptor deletion in a model of oxygen induced retinopathy|
|Anno del prodotto:||2015|
|Digital Object Identifier (DOI):||10.1167/iovs.14-15263|
|Appare nelle tipologie:||1.1 Articolo in rivista|