title: The Nicotinic Cholinergic Pathway Contributes to Retinal Neovascularization in a Mouse Model of Retinopathy of Prematurity.
abstract: To investigate the role of nicotinic acetylcholine receptors (nAChRs) in retinal vascular development and ischemia-induced retinal neovascularization (NV).
  
  
  
  The expression of nAChR subtypes and VEGF signaling pathway components was assessed in mice with and without oxygen-induced ischemic retinopathy by comparing expression levels at postnatal day (P) 14 and P17 in mice exposed to 75% oxygen from P7 to P12 and returned to room air versus mice pups that were exposed to ambient oxygen levels during the same period. The effect of topical or intraocular injection of mecamylamine, a nonspecific nAChR antagonist, or targeted deletion of α7- or α9-nAChRs on ischemia-induced retinal NV was determined by comparing the amount of retinal NV at P17 in these mice versus appropriate controls.
  
  
  
  The expression of nAChR subunits and components of the VEGF signaling pathways was increased in ischemic retina. Topical application or intraocular injection of mecamylamine decreased retinal NV in this model. Mecamylamine had no effect on normal retinal vascular development or on revascularization of the central retinal area of nonperfusion in mice with ischemic retinopathy. Targeted deletion of α9, but not α7, nAChR receptor subunits reduced retinal NV in mice with ischemic retinopathy.
  
  
  
  These data suggest that nAChR signaling, primarily through the α9 nAChR subunit, contributes to ischemia-induced retinal NV, but not retinal vascular development. Mecamylamine or a specific α9 nAChR antagonist could be considered for treatment of retinopathy of prematurity and other ischemic retinopathies.
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Hackett
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Seidel
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Stanford, California, United States.
authors.forename: Sheena
authors.initials: S
authors.lastname: Abraham
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Rishi
authors.initials: R
authors.lastname: Chadha
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Seth D
authors.initials: SD
authors.lastname: Fortmann
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
authors.affiliation: Department of Cardiovascular Sciences, Methodist Hospital System, Houston, Texas, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018678:Cholinergic Agents; D004195:Disease Models, Animal; D007511:Ischemia / Q000378:metabolism; D008464:Mecamylamine / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000627:therapeutic use; D021122:Protein Subunits / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy / Q000378:metabolism*; D012171:Retinal Vessels / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D018678:Cholinergic Agents; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D042461:Vascular Endothelial Growth Factor A; D008464:Mecamylamine; D040301:Vascular Endothelial Growth Factor Receptor-2