The present study focuses on the evaluation of the protective effect on retinal neovascularization exerted by melanocortin receptor 1-5 (MCR 1-5) agonists in a mouse model of proliferative retinopathy induced by intravitreal injection of vascular endothelial growth factor 165 (VEGF165). Methods: Intravitreal injections of the MCR1 agonist BMS-470539 and of the MCR5 agonist PG-901 were performed 7 days before the VEGF165 injection and 1 day after VEGF165 injection. Fluorescein angiography (FAG),

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... immunohistochemical and biochemical analysis were performed at different time points during the follow up. Results: FAG showed a marked vascular tortuosity accompanied by retinal neovascularization in mice receiving VEGF165 intravitreal injection and the absence of neovascularization in mice treated with MCR 1-5 agonists, confirmed by CD34 antigen immunostaining. The biochemical analysis of retinal VEGFR2 gene and protein expression showed that MCR 1-5 agonists significantly reduced VEGFR2 levels, increasing in parallel retinal mir-150 expression. Conclusions: According to these evidences, we propose that intravitreal injections of melanocortin receptor agonists up-regulate mir-150 expression, and this consequently reduces VEGFR2 expression levels with the endpoint being the blockade of VEGF165 induced retinopathy.