The prevalence of myopia and high myopia has gradually increased,increased myopia is associated with an enhanced risk of pathological ocular complications and may lead to blinding disorders.The optometrists and parents initially pay more attention to juvenile myopia prevention and control.Atropine is the previous drug used to control myopia,and the evidence-based medicine has corroborated its clinical effect.However,its mechanism has been undetermined yet.It has been reported that the effective locations of atropine in inhibiting experimental myopia may be not related to the accommodation of ciliary muscle or the ciliary muscle is not the primary target,more and more attention is currently focused on the retina and sclera.Recently,the application of the highly selective muscarinic receptor antagonists and the combination of other drugs have been found that atropine exerts its myopia-controlling effect may be linked to multiple M receptors,and with the secretion and expression of dopamine,nitric oxide (NO),early grow response (EGR)-1,the protein change of the sclera and γ-aminobutyric acid (GABA) ergic signaling pathway.This paper reviewed the atropine on controlling experimental myopia in effective locations and its relationship with the cholinergic pathway,the dopamine pathway,the GABA pathway,the secretion of NO,the expression of EGR-1,and the process of scleral remodeling,hence offers the prospects for the study of atropine in myopia control.

The prevalence of myopia and high myopia has gradually increased,increased myopia is associated with an enhanced risk of pathological ocular complications and may lead to blinding disorders. The optometrists and parents initially pay more attention to juvenile myopia prevention and control. Atropine is the previous drug used to control myopia,and the evidence.based medicine has corroborated its clinical effect. However,its mechanism has been undetermined yet. It has been reported that the effective locations of atropine in inhibiting experimental myopia may be not related to the accommodation of ciliary muscle or the ciliary muscle is not the primary target, more and more attention is currently focused on the retina and sclera. Recently, the application of the highly selective muscarinic receptor antagonists and the combination of other drugs have been found that atropine exerts its myopia.controlling effect may be linked to multiple M receptors,and with the secretion and expression of dopamine,nitric oxide ( NO) , early grow response (EGR).1,the protein change of the sclera and γ.aminobutyric acid (GABA)ergic signaling pathway. This paper reviewed the atropine on controlling experimental myopia in effective locations and its relationship with the cholinergic pathway, the dopamine pathway, the GABA pathway, the secretion of NO, the expression of EGR.1,and the process of scleral remodeling,hence offers the prospects for the study of atropine in myopia control.

Objective:To observe the prevention and control effect of 1% atropine on the progression of form deprivation myopia (FDM) in guinea pigs and the potential biological mechanism.Methods:Sixty-nine 3-week-old tricolor guinea pigs with normal refraction were randomly divided into a normal control group ( n=19), a FDM group ( n=19), a FDM+ atropine group ( n=19), and an atropine group ( n=12). No intervention was given to guinea pigs in normal control group.The FDM model was established by covering the right eye of guinea pigs with a semitransparent latex facemask for 4 weeks in FDM and FDM+ atropine groups.For the FDM+ atropine group, 1% atropine gel was topically administered to the form-deprived right eyes once a day for 4 weeks.For the atropine group, the right eye was treated with 1% atropine gel once a day for 4 weeks.Refraction and axial length of guinea pigs were measured by retinoscopy and ophthalmic A-scan ultrasonography respectively at baseline, experiment week 2 and week 4.In experiment week 4, eyeballs were enucleated to make sections via the paraffin wax processing procedure, and the microstructural and ultrastructural changes of the sclera were observed under the light microscope and transmission electron microscope, respectively.The isobaric tags for relative and absolute quantitation labeling combined with liquid chromatography-tandem mass spectrometry were used to identify the differentially expressed proteins.Use and care of the animals complied with the Regulation for the Administration of Affairs Concerning Experiment Animals by State Science and Technology Commission.The study protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (No.TJYY2020111028). Results:There were statistically significant differences in the diopter of guinea pigs at different time points among the four groups ( Fgroup=138.892, P<0.001; Ftime=167.270, P<0.001). Compared with normal control group, the diopter of guinea pigs in FDM group at experiment weeks 2 and 4, and FDM+ atropine group at experiment week 4 developed toward myopia, showing statistically significant differences (all at P<0.001). Compared with FDM group, the diopter of guinea pigs in FDM+ atropine group at experiment weeks 2 and 4 developed toward hyperopia, showing statistically significant differences (both at P<0.001). There were statistically significant differences in the axial length of guinea pigs at different time points among the four groups ( Fgroup=32.346, P<0.001; Ftime=353.797, P<0.001). The axial lengths of FDM group at experiment weeks 2 and 4 and FDM+ atropine group at experiment week 4 were longer than those of normal control group, and the axial lengths in FDM+ atropine group at experiment weeks 2 and 4 were shorter than those in FDM group, and the differences were statistically significant (all at P<0.001). The collagenous fibers of posterior sclera of guinea pigs were loose and disordered in FDM group, and were regular in FDM+ atropine group.The posterior scleral thickness of normal control group, FDM group, FDM+ atropine group and atropine group was (141.74±16.98), (101.46±9.15), (112.74±6.24) and (134.30±18.19) μm, respectively, with a statistically significant difference ( F=6.709, P=0.005). The posterior sclera was significantly thinner in FDM group than in normal control group and FDM+ atropine group (both at P<0.05). The diameter of posterior scleral collagen fiber gradually increased from inside to outside in normal control group, FDM+ atropine group and atropine group, and the diameters of the inner, middle and outer posterior scleral collagen fibers were smaller in FDM group than in normal control group.Proteomic analysis revealed 85 differentially expressed proteins (fold change>1.30) between FDM group and normal control group, FDM+ atropine group and FDM group, of which 38 were up-regulated and 47 were down-regulated after atropine treatment.Gene Ontology enrichment analysis showed that biological processes mainly involved were biological regulation, cell process, localization and metabolic process.Molecular function mainly involved were binding, catalytic activity, molecular function regulator, structural molecule activity and transporter activity.Cell components mainly involved were in cellular anatomical entity, intracellular and protein-containing complex. Conclusions:Atropine can increase the diameter of scleral collagen fibers in guinea pigs of FDM model, improve the arrangement of scleral collagen fiber, inhibit scleral thinning.The mechanism of atropine to control myopia progression is closely related to the tight junction between scleral cells, cytoskeleton and extracellular matrix remodeling.