Abstract：
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).
摘要：
毒蕈碱胆碱能拮抗剂阿托品是最广泛使用的药物治疗视觉障碍近视（近视），全球低视力的主要原因。这项研究试图更好地定义阿托品抑制近视生长的机制。虽然被归类为毒蕈碱-胆碱能拮抗剂，已发现阿托品结合并调节几种非胆碱能系统的活性（例如，血清素）。因此，这项研究调查了5-羟色胺能系统是否可能低于阿托品的抗近视作用。使用近视眼的小鸡模型，我们报告说，阿托品的生长抑制作用可以通过药物刺激5-羟色胺系统减弱。这可能表明阿托品可以通过抑制5-羟色胺能受体活性来减缓近视的发展。我们还观察到，5-羟色胺能受体的药理拮抗作用以剂量依赖性方式抑制实验性近视的发展，进一步证明调节5-羟色胺能受体活性可以改变眼部生长速率。最后,我们发现无论是实验性近视，也没有阿托品治疗,诱导视网膜5-羟色胺能输出的显著变化(即，合成，运输,释放和分解代谢)。这可能表明,虽然近视生长可以通过调节5-羟色胺能受体活性（通过阿托品或5-羟色胺能拮抗剂）来抑制，这不需要改变血清素水平。关于阿托品的5-羟色胺能机制的这些发现可能对治疗人类近视产生重大影响。这包括评估阿托品在也正在接受治疗以上调5-羟色胺能信号传导的患者中的使用（例如，血清素能抗抑郁药）。
