The beta-adrenergic system interferes with several angiogenesis-dependent diseases. This study investigated the role of the beta-adrenergic system in proliferative retinopathies. In the retina of a mouse model of oxygen-induced retinopathy, we have shown that hypoxia upregulates VEGF and promotes neovascularization. These effects are accompanied by increased levels of norepinephrine suggesting that angiogenic events may depend on increased sympathetic transmission. We have also found that systemic administration of i. non-selective beta adrenergic receptor (b-AR) blocker propranolol, ii. b2-AR blocker ICI 118,551 and iii. non-selective b-AR agonist isoproterenol, which desensitizes b2-ARs, downregulates VEGF and reduces proangiogenic effects of hypoxia. These results have been confirmed by recent studies using topical application of propranolol indicating that b-AR blockers reach the retina and are effective in counteracting hypoxia-induced angiogenesis. In retinal explants, we have also revealed the role of b3-ARs in hypoxia-associated events by demonstrating that b3-AR blockade prevents VEGF upregulation acting through iNOS/NO, suggesting that iNOS inhibition could be a target in preventing the increase in angiogenesis-associated factors. Although extrapolation of these findings to the human situation is difficult, we suggest that b-ARs may represent a target for therapeutic intervention against proliferative retinopathies.

Grant of Meyer Foundation to PB and of IRRF to MDM