Canonical Wnt Signaling Drives Myopia Development and Can Be Pharmacologically Modulated

Background: Myopia has emerged as a major health issue in the world, due to the sight-threatening pathologies associated with high myopia. Even though previous studies have implicated that myopia is determined by a complex interaction of environmental and genetic factors, the pathogenesis of this disease remains unclear. Methods: Here we utilized plasma from patients with myopia, myopic animal models including the adenomatous polyposis coli (APC) gene mutation mouse model, and the form deprivation induced mouse model of myopia. Findings: Using these systems, we demonstrated that the over-activation of canonical Wnt pathway is associated with myopia. Moreover, inhibition of canonical Wnt signaling in mouse models markedly reduced axial elongation, resulting in myopia regression. Interpretation: Together, these results suggest that dysregulation of canonical Wnt signaling is a characteristic of myopia and suggest that targeting Wnt signaling pathways has potential as a therapeutic strategy for myopia. Funding Statement: This study was supported by the Natural Science Foundation of Fujian (No. 2019J05007, ZL); National Basic Research Program of China (Project 973) (No.2011CB50460); National Key Program of China (No. 2018YFA0107304); and National Natural Science Foundation of China (No.81870627). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Approval was received from the Human Ethics committee of Xiamen Eye Center Affiliated to Xiamen University, in accordance with the Declaration of Helsinki. Informed consents were obtained from all subjects after explanation of the nature and possible consequences of the study. Mice were used, treated, and cared for in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and the Guidelines of the Animal Experimental Committee of Xiamen University.