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

Veluchamy A Barathi,Sung Rhan Weon,Eranga N Vithana,Jia Lin Kwan,Liang Kee Goh,Li Fong Seet,Roger W Beuerman,Queenie S W Tan

doi:10.1242/dmm.010967

Veluchamy A Barathi, Sung Rhan Weon + Show 6 more

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https://doi.org/10.1242/dmm.010967

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Abstract

SUMMARYMyopia 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.

Highlights

Myopia is the most common human ocular disorder
They found that mutant mice lacking the muscarinic cholinergic receptor-2 (M2) receptor encoded by the Chrm2 gene are less susceptible to the induction of experimental myopia than are wild-type mice and mice lacking the M1, M4 or M5 subtypes
Choosing M2 knockout mice for further analysis, they show that these mice express higher levels of type I collagen and lower levels of type 5 collagen compared with wild-type mice

Summary

Introduction

Myopia is the most common human ocular disorder. In the United States, one third of the adult population has some degree of myopia (Vitale et al, 2008). In addition to the associated substantial visual loss and economic burden, high myopia [spherical equivalent >6 diopter (D)] has been associated with degenerative diseases such as myopic macular degeneration, retinal detachment and posterior staphyloma (Hotchkiss and Fine, 1981; Metlapally et al, 2008). These lifelong disease issues make myopia a long-term economic and social burden on the health care system (Curtin, 1985; Javitt and Chiang, 1994; Vitale et al, 2006).

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