Abstract：Objective: To investigate the improvement effect of atropine (ATR) on form deprivation myopia model rats by regulating Wnt/β-catenin (β-catenin) signaling pathway and related mechanisms. Methods: Sixty SD rats were randomly grouped into control (NC) group, form deprivation myopia model (Model) group, ATR group (3mg/kg), TAK-715 group (10mg/kg Wnt/β- catenin pathway activator TAK-715), and ATR+TAK-715 group (3mg/kg ATR+10mg/kg TAK-715), with 12 per group. The right eye of NC group and Model group was subconjunctively injected with equal amount of normal saline. After 4 weeks, the axial length and diopter of the right eye of the rats in each group were recorded; the morphology of sclera was observed by HE staining; ELISA kits were used to detect the levels of serum interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α); RT-qPCR was used to detect the mRNA expression of scleral tissue transforming growth factor β1 (TGF-β1), matrix metalloproteinase 2 (MMP-2), and matrix metalloproteinase inhibitor-2 (TIMP-2); Western blot was used to detect the expression of Wnt/β-catenin pathway proteins in sclera tissue. Results: The sclera of the rats in the NC group was normal; the sclera in the Model group became thinner, and the collagen fibers were sparsely arranged and disordered; the thickness of sclera and the diameter of collagen fibers increased in ATR group; the sclera thickness of the rats in the ATR+TAK-715 group decreased, and the fibers were arranged disorderly. Compared with the normal sclera in the NC group, the axial length, refraction, the levels of IL-1β, IL-6 and TNF-α, the mRNA level of MMP-2, and the protein levels of Wnt and MMP-2 in the Model group were obviously increased (P<0.05), the mRNA levels of TGF-β1 and TIMP-2, and the protein levels of TGF-β1, TIMP-2, and p-β-catenin/β-catenin were obviously decreased (P<0.05); compared with the Model group, the axial length, refraction, the levels of IL-1β, IL-6 and TNF-α, the mRNA level of MMP-2, and the protein levels of Wnt and MMP-2 in the ATR group were obviously decreased (P<0.05), the mRNA levels of TGF-β1 and TIMP-2, and the protein levels of TGF-β1, TIMP-2, and p-β-catenin/β-catenin were obviously increased (P<0.05), the corresponding index of TAK-715 group showed the opposite trends (P<0.05); compared with the ATR group, the axial length, refraction, the levels of IL-1β, IL-6 and TNF-α, the mRNA level of MMP-2, and the protein levels of Wnt and MMP-2 in the ATR+TAK-715 group were obviously increased (P<0.05), the mRNA levels of TGF-β1 and TIMP-2, and the protein levels of TGF-β1, TIMP-2, and p-β-catenin/β-catenin were obviously decreased (P<0.05). Conclusion: ATR may reduce inflammatory response and inhibit extracellular matrix remodeling by regulating the Wnt/β-catenin pathway, thereby improving form deprivation myopia in rats.
李锡谦, 康平, 周玉. 阿托品对形觉剥夺性近视模型大鼠的改善作用及作用机制[J]. 河北医学, 2023, 29(1): 76-81.
LI Xiqian, KANG Ping, ZHOU Yu. Ameliorative Effects and Mechanism of Action of Atropine in Rats with Form Deprivation Myopia Model. HeBei Med, 2023, 29(1): 76-81.
[1] Morgan IG,Rose KA.Myopia:is the nature-nurture debate finally over[J].Clin Exp Optom,2019,102(1):3-17. [2] Naidoo KS,Fricke TR,Frick KD,et al.Potential lost productivity resulting from the global burden of myopia:systematic review,meta-analysis,and modeling[J].Ophthalmology,2019,126(3):338-346. [3] Chierigo A,Ferro-Desideri L,Traverso CE,et al.The role of atropine in preventing myopia progression:an update[J].Pharmaceutics,2022,14(5):900-913. [4] Zhao C,Cai C,Ding Q,et al.Efficacy and safety of atropine to control myopia progression:a systematic review and meta-analysis[J].BMC Ophthalmol,2020,20(1):478-485. [5] Chen N,Wang J.Wnt/β-catenin signaling and obesity[J].Front Physiol,2018,9(1):792-806. [6] 张新,巨朝娟,张剑,等.形觉剥夺性近视模型大鼠巩膜成纤维细胞中TGF-β1表达及Wnt/β-catenin信号通路的调控作用[J].吉林大学学报(医学版),2019,45(4):861-866. [7] Liu B,Li N,Zhang J,et al.The role of voltage-gated sodium channel 1.8 in the effect of atropine on heart rate:evidence from a retrospective clinical study and mouse model[J].Front Pharmacol,2020,11(1):1163-1173. [8] Ren H,Zuo S,Hou Y,et al.Inhibition of α1-adrenoceptor reduces TGF-β1-induced epithelial-to-mesenchymal transition and attenuates UUO-induced renal fibrosis in mice[J].Faseb,2020,34(11):14892-14904. [9] Cooper J,Tkatchenko AV.A review of current concepts of the etiology and treatment of myopia[J].Eye Contact Lens,2018,44(4):231-247. [10] Chuang MN,Fang PC,Wu PC.StepWnte low concentration atropine for myopic control:a 10-year cohort study[J].Sci Rep,2021,1(1):17344. [11] Wu PC,Chuang MN,Choi J,et al.Update in myopia and treatment strategy of atropine use in myopia control[J].Eye (Lond),2019,33(1):3-13. [12] 刘奇奇,高洪莲,刘蓓,等.康柏西普对豚鼠形觉剥夺性近视的干预作用及相关机制分析[J].眼科新进展,2020,40(8):722-726. [13] Wei CC,Kung YJ,Chen CS,et al.Allergic conjunctivitis-induced retinal inflammation promotes myopia progression[J].EBioMedicine,2018,28(1):274-286. [14] Hu S,Ouyang S,Liu H,et al.The effect of Wnt/β-catenin pathway on the scleral remolding in the mouse during form deprivation[J].Int Ophthalmol,2021,41(9):3099-3107. [15] Suo NC,Lei CL,Zhang YC,et al.Effects of latanoprost on the expression of TGF-β1 and Wnt / β-catenin signaling pathway in the choroid of form-deprivation myopia rats[J].Cell Mol Biol (Noisy-le-grand),2020,66(6):71-75.
2023, Vol. 29 
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