Pharmacology of myopia and potential role for intrinsic retinal circadian rhythms.
Pharmacology of myopia and potential role for intrinsic retinal circadian rhythms.
复制标题
近视的药理学和内在视网膜昼夜节律的潜在作用。
DOI：
10.1016/j.exer.2013.01.001
复制
发表时间：
2013-09
影响因子：
3.4
通讯作者：
Khurana TS
中科院分区：
文献类型：
--
作者：
Stone RA;Pardue MT;Iuvone PM;Khurana TS
尽管屈光不正的发病率很高，对公众健康的影响也很大，但导致屈光不正的机制却鲜为人知。现在许多证据支持视网膜是调节正视化和潜在屈光不正的机制(S)的中心的概念。利用多种药理学方法和明确的实验动物眼生长模型，许多视网膜神经递质和神经调节剂参与了这一过程。尽管如此，目前还缺乏一个公认的框架来理解支配出生后眼睛发育的分子和/或细胞途径。在这里，我们回顾了两个被广泛研究的信号通路，它们在屈光发育中的一般作用得到了实验和临床数据的支持：通过M胆碱和/或烟碱受体的乙酰胆碱信号和视网膜多巴胺药理学。大约两个世纪前，M受体拮抗剂阿托品作为一种抗近视药物首次被研究，随后的许多工作继续将M受体与眼睛生长调节联系起来。最近的研究表明尼古丁型乙酰胆碱受体具有潜在的作用；在被动暴露于香烟烟雾的人群调查中的屈光效应支持临床相关性。在这里回顾，许多令人费解的结果阻碍形成一个解释乙酰胆碱在屈光发育中作用的机制框架。如何利用胆碱能受体机制来开发可接受的方法以使屈光发育正常化仍然是一个挑战。视网膜多巴胺信号不仅在屈光发育中起重要作用，而且它的光上调是视网膜时钟网络的重要组成部分，并有助于调节视网膜的昼夜生理。在出生后的发育过程中，眼睛的尺寸会经历昼夜和/或昼夜的大小波动；这些节律在实验性屈光不正的眼睛中发生变化。特别是长期存在的近视临床观点认为，环境照明在其中起到了一定的作用，尽管这些推测的分子或细胞机制仍不清楚。配戴凹面眼镜导致的实验性近视改变了视网膜中相当大比例的内在生物钟基因，以及编码褪黑素受体和黑色素的基因。综上所述，这些证据提出了一种假设，即视网膜时钟和内在的视网膜昼夜节律可能是调节屈光发育的机制(S)的基础，并且昼夜信号的中断可能会产生屈光不正。在这里，我们回顾了生物节律在屈光发育中的潜在作用。虽然未来还需要更多的研究，但这一假说可以统一许多不同的临床和实验室观察，以解决屈光不正的发病机制。
Despite the high prevalence and public health impact of refractive errors, the mechanisms responsible for ametropias are poorly understood. Much evidence now supports the concept that the retina is central to the mechanism(s) regulating emmetropization and underlying refractive errors. Using a variety of pharmacologic methods and well-defined experimental eye growth models in laboratory animals, many retinal neurotransmitters and neuromodulators have been implicated in this process. Nonetheless, an accepted framework for understanding the molecular and/or cellular pathways that govern postnatal eye development is lacking. Here, we review two extensively studied signaling pathways whose general roles in refractive development are supported by both experimental and clinical data: acetylcholine signaling through muscarinic and/or nicotinic acetylcholine receptors and retinal dopamine pharmacology. The muscarinic acetylcholine receptor antagonist atropine was first studied as an anti-myopia drug some two centuries ago, and much subsequent work has continued to connect muscarinic receptors to eye growth regulation. Recent research implicates a potential role of nicotinic acetycholine receptors; and the refractive effects in population surveys of passive exposure to cigarette smoke, of which nicotine is a constituent, support clinical relevance. Reviewed here, many puzzling results inhibit formulating a mechanistic framework that explains acetylcholine’s role in refractive development. How cholinergic receptor mechanisms might be used to develop acceptable approaches to normalize refractive development remains a challenge. Retinal dopamine signaling not only has a putative role in refractive development, its upregulation by light comprises an important component of the retinal clock network and contributes to the regulation of retinal circadian physiology. During postnatal development, the ocular dimensions undergo circadian and/or diurnal fluctuations in magnitude; these rhythms shift in eyes developing experimental ametropia. Long-standing clinical ideas about myopia in particular have postulated a role for ambient lighting, although molecular or cellular mechanisms for these speculations have remained obscure. Experimental myopia induced by the wearing of a concave spectacle lens alters the retinal expression of a significant proportion of intrinsic circadian clock genes, as well as genes encoding a melatonin receptor and the photopigment melanopsin. Together this evidence suggests a hypothesis that the retinal clock and intrinsic retinal circadian rhythms may be fundamental to the mechanism(s) regulating refractive development, and that disruptions in circadian signals may produce refractive errors. Here we review the potential role of biological rhythms in refractive development. While much future research is needed, this hypothesis could unify many of the disparate clinical and laboratory observations addressing the pathogenesis of refractive errors.
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DOI：
10.1124/jpet.108.146464
发表时间：
2009-02
影响因子：
3.5
作者：
Chebib, Mary;Hinton, Tina;Schmid, Katrina L.;Brinkworth, Darren;Qian, Haohua;Matos, Susana;Kim, Hye-Lim;Abdel-Halim, Heba;Kumar, Rohan J.;Johnston, Graham A. R.;Hanrahan, Jane R.
通讯作者：
Hanrahan, Jane R.
影响因子：
1.8
作者：
Cohen, Yuval;Belkin, Michael;Polat, Uri
通讯作者：
Polat, Uri
影响因子：
9.8
作者：
Bellingham, James;Chaurasia, Shyam S.;Lucas, Robert J.
通讯作者：
Lucas, Robert J.
DOI：
10.1046/j.1365-8711.2001.04882.x
发表时间：
2001-12-11
影响因子：
4.8
作者：
Cinzano, P;Falchi, F;Elvidge, CD
通讯作者：
Elvidge, CD
影响因子：
1.6
作者：
Chapell, M;Sullivan, B;Pasquarella, A
通讯作者：
Pasquarella, A