%0 Journal Article
%A Lavine, Jeremy
%A Wang, Shoujian
%A DARJATMOKO, SOESIAWATI
%A Wright, Lynda S
%A Gamm, David M
%A Ip, Michael S
%A Sheibani, Nader
%T beta2-Adrenergic receptor antagonism attenuates CNV through Inhibition of VEGF and IL-6 expression
%B Investigative Ophthalmology & Visual Science
%D 2016
%J Investigative Ophthalmology & Visual Science
%V 57
%N 12
%P 4995-4995
%@ 1552-5783
%X    The role of beta-adrenergic signaling in neovascular retinal and choroidal disease has recently emerged. We previously reported that propranolol inhibits choroidal neovascularization (CNV) in vivo and beta2-adrenoreceptor blockade reduces vascular endothelial growth factor (VEGF) expression in vitro. Here we tested the hypothesis that beta2-adrenergic receptors regulate CNV in vivo, investigated the role of beta2-adrenoreceptors in inflammatory signaling, and extended these results into primary human cells.    Mice were subjected to laser burns, inducing CNV, and were treated with a single intravitreal dose of beta2-adrenoreceptor antagonist (ICI 118,551). After 14 days, neovascularization was measured on choroidal-scleral flatmounts using intercellular adhesion molecule-2 immunofluorescence staining. The effect of beta-adrenoreceptor signaling on the expression of VEGF and interleukin 6 (IL-6) was investigated in primary mouse choroidal endothelial cells, retinal pigment epithelial (RPE) cells, microglia cells, and human fetal RPE cells using specific beta-adrenoreceptor agonists and antagonists.    Intravitreal injection of ICI 118,551 reduced CNV by 40% compared to vehicle control (N=30, p<0.01). In primary mouse microglia cells, norepinephrine and the beta2-specific adrenoreceptor agonist formoterol increased Vegf mRNA expression 4-fold, while propranolol and ICI 118,551 prevented norepinephrine-stimulated Vegf mRNA expression. In primary mouse microglia, RPE, and choroidal endothelial cells, norepinephrine elevated IL-6 mRNA expression 9-fold, 24-fold, and 12-fold, respectively. This effect was completely inhibited by both propranolol and ICI 118,551 in all cell types. In primary human fetal RPE cells, norepinephrine and formoterol increased Vegf mRNA expression 2-fold.    beta2-adrenergic receptor antagonism reduces laser-induced CNV in vivo and decreases Vegf and IL-6 mRNA expression in vitro. Anti-VEGF therapy for CNV is effective for most patients; however, some patients are resistant to therapy while other patients undergo a significant burden of repeated treatments and high cost. The beta2-adrenoreceptor is a potential therapeutic target for CNV lesions because of its combined anti-angiogenic and anti-inflammatory properties.  This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016. 
%[ 4/21/2021