Attenuation of Choroidal Neovascularization by beta(2)-Adrenoreceptor Antagonism

作者：Lavine Jeremy A; Sang Yanzhi; Wang Shoujian; Ip Michael S; Sheibani Nader^*

来源：JAMA Ophthalmology, 2013, 131(3): 376-382.

DOI：10.1001/jamaophthalmol.2013.1476

Objectives: To determine whether beta-adrenergic blockade inhibits choroidal neovascularization (CNV) in a mouse model of laser-induced CNV and to investigate the mechanism by which beta-adrenoreceptor antagonism blunts CNV.
Design: Mice were subjected to laser burns, inducing CNV, and were treated with daily intraperitoneal injections of propranolol hydrochloride. Neovascularization was measured on choroidal-scleral flat mounts using intercellular adhesion molecule 2 immunofluorescence staining. The effect of beta-adrenoreceptor signaling on expression of vascular endothelial growth factor (VEGF) was investigated using primary mouse choroidal endothelial cells (ChECs) and retinal pigment epithelial (RPE) cells. These cells were incubated with beta-adrenoreceptor agonists and/or antagonists and assayed for Vegf messenger RNA and protein levels.
Setting: University of Wisconsin School of Medicine and Public Health.
Participants: Wild-type 6-week-old female C57BL/6j mice.
Main Outcome Measures: Inhibition of CNV after propranolol treatment and Vegf messenger RNA and protein expression after treatment with beta-adrenoreceptor agonists and antagonists.
Results: Propranolol-treated mice demonstrated a 50% reduction in laser-induced CNV. Treatment with norepinephrine bitartrate stimulated Vegf messenger RNA expression and protein secretion in ChECs and RPE cells. This effect was blocked by beta(2)-adrenoreceptor antagonism and mimicked by beta(2)-adrenoreceptor agonists.
Conclusions: Attenuation of CNV is achieved by beta-adrenergic blockade. The beta(2)-adrenoreceptors regulate VEGF expression in ChECs and RPE cells.

• 出版日期2013-3