Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Australia.
Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Australia.
Biomed Pharmacother. 2023 Nov;167:115542. doi: 10.1016/j.biopha.2023.115542. Epub 2023 Sep 22.
The muscarinic cholinergic antagonist atropine is the most widely used pharmacological treatment for the visual disorder myopia (short-sightedness), the leading cause of low-vision worldwide. This study sought to better define the mechanism by which atropine inhibits myopic growth. Although classified as a muscarinic-cholinergic antagonist, atropine has been found to bind and modulate the activity of several non-cholinergic systems (e.g., serotonin). Thus, this study investigated whether the serotonergic system could underly atropine's anti-myopic effects. Using a chick model of myopia, we report that atropine's growth-inhibitory effects can be attenuated by pharmacological stimulation of the serotonin system. This may suggest that atropine can slow the development of myopia through inhibiting serotonergic receptor activity. We also observed that pharmacological antagonism of serotonergic receptors inhibits the development of experimental myopia in a dose-dependent manner, further demonstrating that modulation of serotonergic receptor activity can alter ocular growth rates. Finally, we found that neither experimental myopia, nor atropine treatment, induced a significant change in retinal serotonergic output (i.e., synthesis, transport, release and catabolism). This may suggest that, although myopic growth can be inhibited through modulation of serotonergic receptor activity (by atropine or serotonergic antagonists), this does not require a change in serotonin levels. These findings regarding a serotonergic mechanism for atropine may have significant ramifications for the treatment of human myopia. This includes assessing the use of atropine in patients who are also undergoing treatment to upregulate serotonergic signaling (e.g., serotonergic anti-depressants).
毒蕈碱型乙酰胆碱拮抗剂阿托品是治疗视觉障碍近视（远视）最广泛使用的药理学治疗方法，近视是全球低视力的主要原因。本研究旨在更好地定义阿托品抑制近视增长的机制。尽管阿托品被归类为毒蕈碱型乙酰胆碱拮抗剂，但已发现它可以结合并调节几种非胆碱能系统（例如 5-羟色胺）的活性。因此，本研究调查了 5-羟色胺系统是否可以作为阿托品抗近视作用的基础。使用小鸡近视模型，我们报告说，阿托品的生长抑制作用可以通过 5-羟色胺系统的药理学刺激来减弱。这可能表明，阿托品可以通过抑制 5-羟色胺受体活性来减缓近视的发展。我们还观察到，5-羟色胺受体的药理学拮抗作用以剂量依赖的方式抑制实验性近视的发展，进一步表明调节 5-羟色胺受体活性可以改变眼球生长速度。最后，我们发现实验性近视或阿托品治疗均未引起视网膜 5-羟色胺输出（即合成、转运、释放和代谢）的显著变化。这可能表明，尽管可以通过调节 5-羟色胺受体活性（通过阿托品或 5-羟色胺拮抗剂）来抑制近视生长，但这不需要改变 5-羟色胺水平。这些关于阿托品的 5-羟色胺机制的发现可能对人类近视的治疗具有重要意义。这包括评估阿托品在接受上调 5-羟色胺信号（例如 5-羟色胺抗抑郁药）治疗的患者中的使用。
