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多巴胺信号和近视发展:关键的挑战是什么? Dopamine signaling and myopia development: What are the key challenges

Zhou, X., Pardue, M.T., Iuvone, P.M., Qu, J.

期刊名称:Progress in Retinal and Eye Research



摘要:面对过去几十年来近视的增加,以及预计到本世纪末近视患病人数将达到25亿,迫切需要开展有效和安全的治疗干预措施,以减缓这种“近视剧增”,并预防近视相关并发症和视力下降。多巴胺(DA)是视网膜中重要的神经递质,可介导多种功能,包括视网膜发育,视觉信号传导和屈光发育。流行病学和动物研究支持户外活动与发生近视风险之间存在负相关关系,以及光照与多巴胺释放/信号之间存在密切生物学关系,我们从中受到启发,及时和重要的的研究了DA在近视发展中的作用。本文将重新研究几种关于DA调控近视光控制的关键点:1)细胞外视网膜DA水平的因果作用;2)多巴胺D1D2受体的作用机制; 3)细胞/循环视网膜通路的作用。我们使用药理学,转基因或视觉环境的方法通过改变DADA受体和视觉通路来进行显示因果关系的实验。此外,我们评估了基于DA的治疗策略的安全性问题以及解决这些问题的一些方法。本文确定了将DA信号传导和近视的基础知识从动物研究转化为儿童近视有效药理学治疗的关键问题和挑战。

In the face of an "epidemic" increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this "myopia booming" and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including retina development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children.


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