期刊
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
卷 32, 期 6, 页码 1171-1180出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/IAE.0b013e31823496b8
关键词
adiponectin; age-related macular degeneration; bevacizumab; choroidal neovascularization; mouse model; nicotine acetylcholine receptor; platelet-derived growth factor; smoking; vascular endothelial growth factor; alpha-bungarotoxin
资金
- National Institutes of Health [EY 014623, EY 013335]
- Pat & Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences (Little Rock, AR) [1005705]
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-alpha 7 (nAChR alpha 7) expression was evaluated by immunohistochemistry. Bevacizumab or adiponectin peptide II (APNpII) was injected intravitreally on Day 7 post-laser, and the effects were evaluated on Days 14 and 21. alpha-Bungarotoxin was injected intraperitoneally on Days 2 to 5, and its effect was evaluated on Day 14. Results: Expression of nAChR alpha 7 was 2 to 7 times higher between Days 3 and 7 postlaser compared with naive mice. In water-fed mice, APNpII, bevacizumab, and alpha-bungarotoxin significantly reduced CNV size. In nicotine-fed mice, treatment with APNpII or bevacizumab did not significantly reduce CNV size, whereas alpha-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 alpha-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. nAChR alpha 7 is significantly upregulated during the formation of CNV, and treatment with an nAChR alpha 7 antagonist decreases CNV size irrespective of nicotine administration. RETINA 32:1171-1180, 2012
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