Muscarinic acetylcholine receptor 3 is dominant in myopia progression.
OBJECTIVE
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 2(-ΔΔCt)


METHODS
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 = 0.005). A replication cohort was collected to further confirm the association of CHRM3 CNV with myopia (P = 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.
Department of Ophthalmology, China Medical University, Taichung, Taiwan.
Hui-Ju
HJ
Lin
Lei
L
Wan
Wen-Chi
WC
Chen
Jane-Ming
JM
Lin
Chao-Jen
CJ
Lin
Fuu-Jen
FJ
Tsai
D000293:Adolescent; D000328:Adult; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002874:Chromosome Mapping; D006224:Cricetinae; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008647:Mesocricetus; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009216:Myopia / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2 / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000235:genetics*; D043588:Receptor, Muscarinic M4 / Q000235:genetics; D043642:Receptor, Muscarinic M5 / Q000235:genetics; D011976:Receptors, Muscarinic / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult
C086088:CHRM1 protein, human; C487078:CHRM2 protein, human; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D043642:Receptor, Muscarinic M5; D011976:Receptors, Muscarinic; D001285:Atropine