First Author | Dal Monte M | Year | 2014 |
Journal | Invest Ophthalmol Vis Sci | Volume | 56 |
Issue | 1 | Pages | 59-73 |
PubMed ID | 25503457 | Mgi Jnum | J:230987 |
Mgi Id | MGI:5766618 | Doi | 10.1167/iovs.14-15263 |
Citation | Dal Monte M, et al. (2015) Protective effects of beta1/2 adrenergic receptor deletion in a model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci 56(1):59-73 |
abstractText | PURPOSE: beta-adrenergic receptors (beta-ARs) regulate angiogenesis in proliferative retinopathies. We studied the effects of beta1/2-AR deletion in a model of oxygen-induced retinopathy (OIR) to confirm the role of beta1- and/or beta2-ARs in regulating angiogenesis and to get insights into the role of beta3-ARs. METHODS: Mice with beta1/2-AR deletion (KO) were used. Levels of norepinephrine (NE), beta3-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 beta3-AR agonist. RESULTS: Oxygen-induced retinopathy was characterized by NE upregulation with higher levels in wild type (WT) than in KO. Wild type and KO displayed comparable levels of beta3-ARs, transcription, and proangiogenic factors, but differed in VEGF receptor (VEGFR) expression with VEGFR-1 in WT lower than in KO and VEGFR-2 in WT higher than in KO. Blood-retinal barrier dysfunction did not differ between WT and KO. Vascular abnormalities in the superficial plexus were abolished by beta1/2-AR deletion, which also helped the development of the deep plexus. In both WT and KO, beta3-AR agonism, acting through the nitric oxide pathway, caused enhanced neovascular responses with increased levels of VEGF. CONCLUSIONS: We confirm that beta1- and beta2-ARs play a pivotal role in retinal angiogenesis. In their presence, beta3-ARs potentiate angiogenic responses, whereas, in their absence, beta3-ARs sustain the angiogenic drive. These results suggest beta-ARs as promising targets for therapies aimed to counteract proliferative retinopathies. |