The effect of nicotine on anti-vascular endothelial growth factor therapy in a mouse model of neovascular age-related macular degeneration.
The effect of nicotine on anti-vascular endothelial growth factor therapy in a mouse model of neovascular age-related macular degeneration.
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DOI：
10.1097/iae.0b013e31823496b8
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Bora PS
中科院分区：
文献类型：
--
作者：
Davis SJ;Lyzogubov VV;Tytarenko RG;Safar AN;Bora NS;Bora PS
评价尼古丁对抗VEGF治疗新生血管性年龄相关性黄斑变性（AMD）的效果。一组小鼠在饮用水中接受尼古丁，另一组仅接受水。用激光诱导脉络膜新生血管（CNV）。通过免疫组织化学（MHC）评价尼古丁乙酰胆碱受体（nAChR）α7的表达。在激光后第7天玻璃体内注射贝伐单抗或脂联素肽II（APNpII），并在第14天和第21天评价效果。在第2-5天腹膜内注射α-银环蛇毒素，并在第14天评价其作用。与未处理小鼠相比，激光后第3天和第7天的nAChR α7表达高2-7倍。在水喂养的小鼠中，APNpII、贝伐单抗和α-银环蛇毒素显著降低CNV大小。在尼古丁喂养的小鼠中，用APNpII或贝伐单抗处理没有显著降低CNV大小，而α-银环蛇毒素确实有影响。比较水和尼古丁小鼠，CNV大小在水小鼠中小61-86%，除了α-银环蛇毒素组没有差异。在尼古丁处理的小鼠中，PDGF和VEGF表达在第14天高1.5-2.5倍。尼古丁显著阻断抗VEGF治疗激光诱导的新生血管性AMD的效果。nAChR α7在CNV形成过程中显著上调，无论尼古丁给药与否，nAChR α7拮抗剂治疗均可降低CNV大小-
Evaluate the effect of nicotine on anti-VEGF therapy in the treatment of neovascular age-related macular degeneration (AMD). 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 (nAChR) α7 expression was evaluated by immunohistochemistry (IHC). Bevacizumab or adiponectin peptide II (APNpII) was injected intravitreally on day 7 post-laser and the effects were evaluated on days 14 and 21. α-bungerotoxin was injected intraperitoneally on days 2–5 and its effect evaluated on day 14. Expression of nAChR α7 was 2–7 times higher between days 3 and 7 post-laser compared to naïve 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-bungerotoxin did have an effect. Comparing water and nicotine mice, CNV size was 61–86% smaller in water mice except for the α-bungarotoxin group where there was no difference. PDGF and VEGF expression was 1.5–2.5 fold higher at day 14 in nicotine treated mice. Nicotine significantly blocks the effect of anti-VEGF therapy in the treatment of laser induced neovascular AMD. nAChR α7 is significantly up-regulated during the formation of CNV and treatment with a nAChR α7 antagonist decreases CNV size irrespective of nicotine administration-