Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice

被引：36

作者：

Barathi, Veluchamy A. ^{[1
,2
,3
]}

Kwan, Jia Lin ^{[1
]}

Tan, Queenie S. W. ^{[1
]}

Weon, Sung Rhan ^{[1
]}

Seet, Li Fong ^{[1
,2
]}

Goh, Liang Kee ^{[3
,4
]}

Vithana, Eranga N. ^{[1
,2
,3
]}

Beuerman, Roger W. ^{[1
,2
,3
]}

机构：

[1] Singapore Eye Res Inst, Singapore 168751, Singapore

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 119074, Singapore

[3] Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore

[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 119074, Singapore

来源：

DISEASE MODELS & MECHANISMS | 2013年 / 6卷 / 05期

基金：

英国医学研究理事会;

关键词：

FORM-DEPRIVATION MYOPIA; PIRENZEPINE OPHTHALMIC GEL; GENOME-WIDE ASSOCIATION; MESSENGER-RNA LEVELS; ACETYLCHOLINE-RECEPTORS; REFRACTIVE ERRORS; SUSCEPTIBILITY LOCUS; MAMMALIAN SCLERA; PARALLEL SAFETY; UNITED-STATES;

D O I：

10.1242/dmm.010967

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 (M-2; 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 M-2 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, M-2 mutant mice were resistant to the development of experimental myopia. Pharmacological blockade of M-2 muscarinic receptor proteins retarded myopia progression in the mouse. These results suggest for the first time a role of M-2 in growth-related changes in extracellular matrix genes during myopia development in a mammalian model. M-2 receptor antagonists might thus provide a targeted therapeutic approach to the management of this refractive error.

引用

页码：1146 / 1158

页数：13