Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Bruce, Canberra, Australia.
Research School of Biology, Australian National University, Acton, Australia.
Invest Ophthalmol Vis Sci. 2024 Sep 3;65(11):29. doi: 10.1167/iovs.65.11.29.
PURPOSE: While previously investigating the mechanism by which atropine inhibits ocular growth, we observed that stimulation of nicotinic receptors can inhibit experimental myopia. This study expands on that preliminary finding and investigates the safety and efficacy of nicotinic stimulation in the inhibition of ocular growth. METHODS: Nicotine's ability to inhibit form-deprivation myopia (FDM), following intravitreal injection (9 chicks per group) or topical application (6 chicks per group), was investigated over three doses. The ability of nicotine to inhibit lens-induced myopia (LIM) was also tested (in 12 chicks). For ocular safety, following 4 weeks of topical treatment with nicotine (n = 10), pupillary reflex, intraocular pressure, corneal curvature/thickness, lens thickness, retinal health (retinal thickness/cell apoptosis), as well as retinal function (electroretinogram recordings) were assessed. We also examined the effects of nicotine on non-ocular autonomic functions in both chicks (n = 5) and mice (n = 5). RESULTS: Nicotine was observed to significantly inhibit the development of FDM in chicks when administered as an intravitreal injection (P < 0.05) or topical eye drops (P < 0.05), albeit not in a dose-dependent manner. Nicotine also inhibited LIM (P < 0.05) to a similar degree to that seen for FDM. Although ocular health was (for the most part) unaffected by nicotine, the highest topical dose induced a temporary reduction in cardiorespiratory output (P < 0.05). CONCLUSIONS: Nicotine, administered as an intravitreal injection or topical eye drop, significantly inhibits the development of experimental myopia. Although the anti-myopic effects observed presently are interesting, the well-reported side effects (expanded on presently) and addictive properties of nicotine would preclude its clinical use.
目的:在研究阿托品抑制眼球生长的机制时,我们观察到烟碱受体的刺激可以抑制实验性近视。本研究扩展了这一初步发现,并研究了烟碱刺激抑制眼球生长的安全性和有效性。
方法:通过玻璃体内注射(每组 9 只鸡)或局部应用(每组 6 只鸡),研究了尼古丁抑制形觉剥夺性近视(FDM)的能力。还测试了尼古丁抑制晶状体诱导性近视(LIM)的能力(12 只小鸡)。为了评估眼部安全性,在使用尼古丁进行 4 周局部治疗后(n = 10),评估了瞳孔反射、眼内压、角膜曲率/厚度、晶状体厚度、视网膜健康(视网膜厚度/细胞凋亡)以及视网膜功能(视网膜电图记录)。我们还检查了尼古丁对小鸡(n = 5)和小鼠(n = 5)的非眼部自主功能的影响。
结果:当以玻璃体内注射(P < 0.05)或局部滴眼剂(P < 0.05)给予尼古丁时,观察到它显著抑制小鸡 FDM 的发展,但不是剂量依赖性的。尼古丁也抑制 LIM(P < 0.05),与 FDM 所见相似。尽管尼古丁在很大程度上没有影响眼部健康,但最高的局部剂量会暂时降低心肺输出(P < 0.05)。
结论:以玻璃体内注射或局部滴眼剂给予的尼古丁显著抑制实验性近视的发展。尽管目前观察到的抗近视效果很有趣,但尼古丁的已知副作用(在本文中进一步阐述)和成瘾性会排除其临床应用。
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