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Abstract #52941 Published in IGR 15-1
Attenuation of choroidal neovascularization by β(2)-adrenoreceptor antagonism
Lavine JA; Sang Y; Wang S; Ip MS; Sheibani NJAMA ophthalmology 2013; 131: 376-382
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.
Departments of Ophthalmology and Visual Science, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Full articleClassification:
11.3.4 Betablocker (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
