Attenuation of choroidal neovascularization by β2- adrenoreceptor antagonism

Jeremy Arlin Lavine, Yanzhi Sang, Shoujian Wang, Michael S. Ip, Nader Sheibani*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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/6jmice. 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 β2-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.

Original languageEnglish (US)
Pages (from-to)376-382
Number of pages7
JournalJAMA ophthalmology
Volume131
Issue number3
DOIs
StatePublished - Mar 2013

ASJC Scopus subject areas

  • Ophthalmology

Fingerprint Dive into the research topics of 'Attenuation of choroidal neovascularization by β<sub>2</sub>- adrenoreceptor antagonism'. Together they form a unique fingerprint.

  • Cite this