The effect of nicotine on anti-vascular endothelial growth factor therapy in a mouse model of neovascular age-related macular degeneration

Retina. 2012 Jun;32(6):1171-80. doi: 10.1097/IAE.0b013e31823496b8.

Abstract

Purpose: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / therapeutic use
  • Analysis of Variance
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Bungarotoxins / pharmacology
  • Choroid / metabolism
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / metabolism
  • Choroidal Neovascularization / pathology
  • Disease Models, Animal
  • Immunohistochemistry
  • Intravitreal Injections
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nicotine / pharmacology*
  • Receptors, Nicotinic / metabolism
  • Retinal Pigment Epithelium / metabolism
  • Vascular Endothelial Growth Factors / antagonists & inhibitors*
  • Vascular Endothelial Growth Factors / metabolism
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Adiponectin
  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Bungarotoxins
  • Chrna7 protein, mouse
  • Receptors, Nicotinic
  • Vascular Endothelial Growth Factors
  • alpha7 Nicotinic Acetylcholine Receptor
  • Bevacizumab
  • Nicotine