title: The effect of nicotine on anti-vascular endothelial growth factor therapy in a mouse model of neovascular age-related macular degeneration.
abstract: OBJECTIVE
  The purpose of this article is to evaluate the effect of nicotine on anti-vascular endothelial growth factor therapy in the treatment of neovascular age-related macular degeneration.
  
  
  METHODS
  One group of mice received nicotine in drinking water and the other group received water only. Choroidal neovascularization (CNV) was induced with a laser. Nicotinic acetylcholine receptor-α7 (nAChRα7) expression was evaluated by immunohistochemistry. Bevacizumab or adiponectin peptide II (APNpII) was injected intravitreally on Day 7 postlaser, and the effects were evaluated on Days 14 and 21. α-Bungarotoxin was injected intraperitoneally on Days 2 to 5, and its effect was evaluated on Day 14.
  
  
  RESULTS
  Expression of nAChRα7 was 2 to 7 times higher between Days 3 and 7 postlaser compared with naive mice. In water-fed mice, APNpII, bevacizumab, and α-bungarotoxin significantly reduced CNV size. In nicotine-fed mice, treatment with APNpII or bevacizumab did not significantly reduce CNV size, whereas α-bungarotoxin did have an effect. Comparing water- and nicotine-fed mice, CNV size was 61% to 86% smaller in water-fed mice except for the α-bungarotoxin group, where there was no difference. Platelet-derived growth factor and vascular endothelial growth factor expression was 1.5- to 2.5-fold higher at Day 14 in nicotine-treated mice.
  
  
  CONCLUSIONS
  Nicotine significantly blocks the effect of anti-vascular endothelial growth factor therapy in the treatment of laser-induced neovascular age-related macular degeneration. nAChRα7 is significantly upregulated during the formation of CNV, and treatment with an nAChRα7 antagonist decreases CNV size irrespective of nicotine administration.
authors.affiliation: Department of Ophthalmology, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Davis
authors.forename: Valeriy V
authors.initials: VV
authors.lastname: Lyzogubov
authors.forename: Ruslana G
authors.initials: RG
authors.lastname: Tytarenko
authors.forename: Ammar N
authors.initials: AN
authors.lastname: Safar
authors.forename: Nalini S
authors.initials: NS
authors.lastname: Bora
authors.forename: Puran S
authors.initials: PS
authors.lastname: Bora
mesh_terms: D052242:Adiponectin / Q000627:therapeutic use; D000704:Analysis of Variance; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D002038:Bungarotoxins / Q000494:pharmacology; D002829:Choroid / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D052242:Adiponectin; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D002038:Bungarotoxins; C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D042442:Vascular Endothelial Growth Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000068258:Bevacizumab; D009538:Nicotine
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