Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice.
Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice.
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DOI：
10.1242/dmm.010967
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发表时间：
2013-09
影响因子：
4.3
通讯作者：
Beuerman RW
中科院分区：
文献类型：
--
作者：
Barathi VA;Kwan JL;Tan QS;Weon SR;Seet LF;Goh LK;Vithana EN;Beuerman RW
近视是一个巨大的全球性公共卫生问题，在亚洲发病率最高。识别易感基因对于理解近视的生物学基础至关重要。在本文中，我们已经确定和特点的功能性近视相关基因使用特定的小鼠敲除模型。与野生型小鼠相比，缺乏毒蕈碱胆碱能受体基因（M2;也称为Chrm 2）的小鼠对镜片诱导的近视不太敏感，野生型小鼠在实验诱导近视时显示出显著增加的眼轴长度和玻璃体腔深度。本研究的关键发现是，M2突变小鼠的巩膜具有比野生型小鼠和其他毒蕈碱亚型突变的小鼠更高的I型胶原蛋白表达和更低的V型胶原蛋白表达，因此，M2突变小鼠对实验性近视的发展具有抗性。M2毒蕈碱受体蛋白的药理学阻断延缓了小鼠的近视进展。这些结果首次表明，在哺乳动物模型近视发展过程中，M2在细胞外基质基因的生长相关变化中发挥作用。因此，M2受体拮抗剂可能提供一种有针对性的治疗方法来管理这种屈光不正。
Myopia is a huge public health problem worldwide, reaching the highest incidence in Asia. Identification of susceptible genes is crucial for understanding the biological basis of myopia. In this paper, we have identified and characterized a functional myopia-associated gene using a specific mouse-knockout model. Mice lacking the muscarinic cholinergic receptor gene (M2; also known as Chrm2) were less susceptible to lens-induced myopia compared with wild-type mice, which showed significantly increased axial length and vitreous chamber depth when undergoing experimental induction of myopia. The key findings of this present study are that the sclera of M2 mutant mice has higher expression of collagen type I and lower expression of collagen type V than do wild-type mice and mice that are mutant for other muscarinic subtypes, and, therefore, M2 mutant mice were resistant to the development of experimental myopia. Pharmacological blockade of M2 muscarinic receptor proteins retarded myopia progression in the mouse. These results suggest for the first time a role of M2 in growth-related changes in extracellular matrix genes during myopia development in a mammalian model. M2 receptor antagonists might thus provide a targeted therapeutic approach to the management of this refractive error.
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影响因子：
--
作者：
Liu, Shaohui;Li, Jing;Beuerman, Roger W.
通讯作者：
Beuerman, Roger W.
影响因子：
4.8
作者：
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通讯作者：
McBrien, NA
影响因子：
1.7
作者：
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通讯作者：
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影响因子：
30.8
作者：
通讯作者：
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影响因子：
4.8
作者：
Gentle, A;Liu, YY;McBrien, NA
通讯作者：
McBrien, NA