Attenuation of choroidal neovascularization by β(2)-adrenoreceptor antagonism.

Michael Ip // Publications // Sheibani Lab // Mar 01 2013

PubMed ID: 23303344

Author(s): Lavine JA, Sang Y, Wang S, Ip MS, Sheibani N. Attenuation of choroidal neovascularization by β(2)-adrenoreceptor antagonism. JAMA Ophthalmol. 2013 Mar;131(3):376-82. doi: 10.1001/jamaophthalmol.2013.1476. PMID 23303344

Journal: Jama Ophthalmology, Volume 131, Issue 3, Mar 2013

OBJECTIVES To determine whether β-adrenergic blockade inhibits choroidal neovascularization (CNV) in a mouse model of laser-induced CNV and to investigate the mechanism by which β-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 β-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 β-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 β-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 β2-adrenoreceptor antagonism and mimicked by β2-adrenoreceptor agonists.

CONCLUSIONS Attenuation of CNV is achieved by β-adrenergic blockade. The β2-adrenoreceptors regulate VEGF expression in ChECs and RPE cells.

CLINICAL RELEVANCE Antagonists of β-adrenoreceptors are safe and well tolerated in patients with glaucoma and cardiovascular disease. Thus, blockade of β-adrenoreceptors may provide a new avenue to inhibit VEGF expression in CNV.