title: Attenuation of choroidal neovascularization by β(2)-adrenoreceptor antagonism.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  University of Wisconsin School of Medicine and Public Health.
  
  
  METHODS
  Wild-type 6-week-old female C57BL/6j mice.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Ophthalmology and Visual Science, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Lavine
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Sang
authors.forename: Shoujian
authors.initials: S
authors.lastname: Wang
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ip
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D011433:Propranolol