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药物基因组学在近视防治药物研发中的应用:路在何方。

Pharmacogenomic Approach to Antimyopia Drug Development: Pathways Lead the Way.

机构信息

Department of Ophthalmology, Columbia University, New York, NY, USA.

Department of Ophthalmology, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.

出版信息

Trends Pharmacol Sci. 2019 Nov;40(11):833-852. doi: 10.1016/j.tips.2019.09.009. Epub 2019 Oct 30.

Abstract

Myopia is the most common eye disorder in the world which is caused by a mismatch between the optical power of the eye and its excessively long axial length. Recent studies revealed that the regulation of the axial length of the eye occurs via a complex signaling cascade, which originates in the retina and propagates across all ocular tissues to the sclera. The complexity of this regulatory cascade has made it particularly difficult to develop effective antimyopia drugs. The current pharmacological treatment options for myopia are limited to atropine and 7-methylxanthine, which have either significant adverse effects or low efficacy. In this review, we focus on the recent advances in genome-wide studies of the signaling pathways underlying myopia development and discuss the potential of systems genetics and pharmacogenomic approaches for the development of antimyopia drugs.

摘要

近视是世界上最常见的眼部疾病,是由眼睛的光学功率与过长的眼轴不匹配引起的。最近的研究表明,眼睛轴长的调节是通过一个复杂的信号级联来发生的,这个信号级联始于视网膜,并在所有眼部组织中传播到巩膜。这个调节级联的复杂性使得开发有效的抗近视药物变得特别困难。目前,近视的药物治疗选择仅限于阿托品和 7-甲基黄嘌呤,它们要么有显著的不良反应,要么疗效低。在这篇综述中,我们专注于与近视发展相关的信号通路的全基因组研究的最新进展,并讨论了系统遗传学和药物基因组学方法在开发抗近视药物方面的潜力。

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引用本文的文献

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Pharmacogenomics.药物基因组学。
Lancet. 2019 Aug 10;394(10197):521-532. doi: 10.1016/S0140-6736(19)31276-0. Epub 2019 Aug 5.
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IMI - Myopia Genetics Report.近视遗传学报告
Invest Ophthalmol Vis Sci. 2019 Feb 28;60(3):M89-M105. doi: 10.1167/iovs.18-25965.
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IMI - Report on Experimental Models of Emmetropization and Myopia.IMI-正视化和近视实验模型报告。
Invest Ophthalmol Vis Sci. 2019 Feb 28;60(3):M31-M88. doi: 10.1167/iovs.18-25967.
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Drug repurposing: progress, challenges and recommendations.药物重定位:进展、挑战和建议。
Nat Rev Drug Discov. 2019 Jan;18(1):41-58. doi: 10.1038/nrd.2018.168. Epub 2018 Oct 12.

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