title: Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice.
abstract: 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.
authors: Singapore Eye Research Institute, 11 Third Hospital Avenue, 168751 Singapore, Singapore.
authors: Veluchamy A
authors: VA
authors: Barathi
authors: Jia Lin
authors: JL
authors: Kwan
authors: Queenie S W
authors: QS
authors: Tan
authors: Sung Rhan
authors: SR
authors: Weon
authors: Li Fong
authors: LF
authors: Seet
authors: Liang Kee
authors: LK
authors: Goh
authors: Eranga N
authors: EN
authors: Vithana
authors: Roger W
authors: RW
authors: Beuerman
mesh_terms: D000328:Adult; D000368:Aged; D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009216:Myopia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012590:Sclera / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000470:Alkaloids; D005663:Furans; D009281:Naphthalenes; D010880:Piperidines; D034741:RNA, Small Interfering; D043585:Receptor, Muscarinic M2; D010890:Pirenzepine; D003094:Collagen; C048172:himbacine; C048593:otenzepad
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