Muscarinic Acetylcholine Receptor 3 Is Dominant in Myopia Progression

Abstract

PURPOSE. Numerous studies have proven that the nonselective muscarinic acetylcholine receptor (mAChR) antagonist atropine prevents the axial elongation that leads to myopia. Five distinct receptor genes (CHRM1-CHRM5), each encoding a muscarinic receptor protein (M[1]-M[5]), have been cloned. Copy number variations (CNVs), which constitute a substantial portion of genetic variability and structural genetic variants, are increasingly being recognized as modulators of human diseases. In this study, CNVs of CHRMs were detected to determine the genes associated with myopia.METHODS. Participants were divided into three groups: high myopia group (myopia of 6-10 diopters [D]), severe high myopia group (myopia ‡10 D), and control group (myopia 0.5 D). The CNVs were detected, and the relative copy number was estimated using the comparative 2ÀDDCt method. Syrian hamsters with form-deprivation myopia (FDM) were used as animal models of myopia.RESULTS. The CNVs of CHRM2, CHRM3, and CHRM4 were significantly different among the groups, and the variations were most dominant in the CHRM3. The CNVs of CHRM3 showed significant differences among all 3 groups (P ¼ 0.005). A replication cohort was collected to further confirm the association of CHRM3 CNV with myopia (P ¼ 0.011). The expression of M(3) on the sclera of the FDM Syrian hamsters was upregulated and then downregulated after atropine administration.CONCLUSIONS. CHRM3 and M(3) were suggested to play important roles in the pathogenesis of myopia and in the arrested progression of myopia by atropine. (Invest Ophthalmol Vis Sci. 2012;53:6519-6525) DOI:10.1167/iovs.11-9031 C linically significant refractive errors are the most common visual disorders. Myopia affects more than half of young adults in the world. [1][2][3] In Asian countries, the prevalence of myopia has approached epidemic proportions.4 Animal studies of myopia have shown that the nonselective muscarinic acetylcholine receptor (mAChR) antagonist atropine effectively prevents the axial elongation that leads to myopia. [5][6][7] Human clinical trials have also shown the effectiveness of daily atropine administration in reducing the progression of myopia. The mAChR family proteins are a group of neurotransmitter proteins that belong to the 7-transmembrane superfamily of receptors. Five distinct receptor genes (CHRM1-CHRM5), each encoding a muscarinic receptor protein (M[1]-M[5]) with specific pharmacological properties, have been cloned. [8][9][10] Different studies have shown the diverse effects of M(1) to M(5) on myopia; moreover, M(1) to M(5) have been proposed to play various roles in the ''stop'' signal of myopic progression. [8][9][10] In vitro studies have shown that mAChR antagonists inhibited scleral proliferation and matrix synthesis. 8-10Many studies have suggested that myopia is a complex condition with multiple causes and develops as a result of interactions between multiple genes and environmental stimuli.11 This study detected CHRM1 to CHRM5 polymorphisms by using the copy number variation (CNV) metho...

Effect of prolonged photoperiod on ocular tissues of domestic turkeys

“…In this same study, suppression of dopaminergic retinal pathways by intravitreal injection of a neurotoxin restored the growth inhibition at night in these chickens . The evidence for dopamine and melatonin playing a role in eye growth is preliminary and other neuromodulators such as glucagon and acetylcholine may be involved. It is conceivable that interrupting diurnal rhythm by exposing turkeys in our study to a prolonged photoperiod led to disturbances in dopamine and melatonin, which in turn resulted in excessive ocular growth.…”

Myopia. Part II – prevention and treatment of the latest guidelines

“…Bardzo ważna zatem jest ocena, czy pacjent ma nadmierną akomodację, czy też niedomogę akomodacji. Drugi ważny mechanizm działania tego leku to jego oddziaływanie na receptory muskarynowe fibroblastów twardówki i jej wpływ na przemodelowanie struktury twardówki (5,16).…”

The Current Management Strategies for Myopia Control in Children: Mini Review

“…Although earlier studies have suggested that atropine may achieve this due to its effects on lens accommodation, more recent studies have shown that the main mechanism is via non-accommodative pathway especially acting directly on receptors in the sclera [3,6,7] which slows axial elongation. Nevertheless, unavoidable side effects of atropine such as near vision blur, photophobia, and glare and rebound after discontinuing treatment which are seen particularly in higher doses have limited its utilization.…”

“…The non-accommodative mechanisms such as creating a myopic shift in the peripheral retina and altering corneal shape by optical interventions [3][4][5], and scleral collagen enhancement by pharmacological agents [3][4][5][6] have gained popularity in myopia control, and significant beneficial outcomes have been reported by many reserachers. This mini-review aimed specifically at investigating the comparative effectiveness of different interventions systematicaly and summarizing data on the myopia control in children from recent studies.…”