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Samy Omri, Houda Tahiri, Jose Carlos Rivera, Isabelle Lahaie, Sylvain Chemtob; Implication of beta-adrenergic receptor in choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4985.
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We investigated the role of beta-adrenergic receptor (b-AR) on choroidal neovascularization (CNV) in an animal model of wet age-related macular degeneration in mice.
The angiogenic effect of the b-AR was evaluated in RPE-choroid explants from C57Bl6 mice stimulated with 10 uM of isoproterenol (an agonist of the receptor) during 24h. Conversely, a classic choroidal neovascularization (CNV) model induced by laser burn in C57Bl6 mice (8 weeks) was used to assess the anti-angiogenic effect of propranolol (an antagonist of the b-AR). In this experiment, mice were treated with intraperitoneal propranolol (6mg/kg/d) or vehicle (saline solution) daily for 10 days, starting on day 4 after laser burn and until sacrifice (day 14). Immunostaining analysis on retinal flatmounts and cryosections were performed to determine the surface of CNV, the distribution of b-AR and the number and morphology of microglia/macrophages associated with CNV. Additionally, retinal expression of the b-AR and VEGF was evaluated by Western blot.
The expression and distribution of the b-1 and b-2 adrenergic receptors was localized in the choroid and RPE cells. The stimulation of RPE-choroid explants with isoproterenol increased approximately 50% choroidal neovascularization compared to vehicle. On the contrary, propranolol inhibited significantly the levels of VEGF and CNV growth in laser burn model compared to the vehicle. Interestingly, the treatment with propranolol decremented the number of activated (amiboid shape) microglia/macrophages but surprisingly, the number of non-activated microglia/macrophages around the CNV was higher than with the vehicle treatment.
These ex vivo and in vivo studies highlight the importance of b-adrenergic receptor in the CNV. Propranolol can inhibit CNV by decreasing the levels of VEGF and modulating microglia/macrophages activation. Further work will investigate the role of b-adrenergic receptor on suppression of the inflammatory environment in order to understand the link between neovascularization and inflammation in CNV during age-related macular degeneration.
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