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Tytuł:
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Canonical Wnt Signaling Drives Myopia Development and Can Be Pharmacologically Modulated.
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Autorzy:
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Liu Z; Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Xiamen University, Xiamen, Fujian, China.; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen University, Xiamen, China.; Fujian Engineering and Research Center of Eye Regenerative Medicine, Xiamen University, Xiamen, Fujian, China.
Xiu Y; Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Qiu F; Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States.
Zhu Z; Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Zong R; Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Xiamen University, Xiamen, Fujian, China.; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen University, Xiamen, China.; Fujian Engineering and Research Center of Eye Regenerative Medicine, Xiamen University, Xiamen, Fujian, China.
Zhou X; School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.; Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
An J; School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.; Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Wang Q; School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.; Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Reinach PS; School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.; Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
Li W; Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Xiamen University, Xiamen, Fujian, China.; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen University, Xiamen, China.; Fujian Engineering and Research Center of Eye Regenerative Medicine, Xiamen University, Xiamen, Fujian, China.
Chen W; Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Xiamen University, Xiamen, Fujian, China.; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen University, Xiamen, China.; Fujian Engineering and Research Center of Eye Regenerative Medicine, Xiamen University, Xiamen, Fujian, China.
Liu Z; Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Xiamen University, Xiamen, Fujian, China.; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen University, Xiamen, China.; Fujian Engineering and Research Center of Eye Regenerative Medicine, Xiamen University, Xiamen, Fujian, China.
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Źródło:
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Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2021 Jul 01; Vol. 62 (9), pp. 21.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Brookline Ma : Association For Research In Vision And Ophthalmology (Arvo)
Original Publication: St. Louis, Mosby.
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MeSH Terms:
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Anterior Eye Segment/*metabolism
Myopia/*genetics
Posterior Eye Segment/*metabolism
Refraction, Ocular/*physiology
Wnt Signaling Pathway/*genetics
Adolescent ; Adult ; Animals ; Anterior Eye Segment/diagnostic imaging ; Anterior Eye Segment/drug effects ; Biomarkers/metabolism ; Disease Models, Animal ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/pharmacokinetics ; Male ; Mice ; Mice, Inbred C57BL ; Myopia/metabolism ; Myopia/physiopathology ; Posterior Eye Segment/diagnostic imaging ; Posterior Eye Segment/drug effects ; Sensory Deprivation ; Young Adult
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Substance Nomenclature:
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0 (Biomarkers)
0 (DKK1 protein, human)
0 (Intercellular Signaling Peptides and Proteins)
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Entry Date(s):
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Date Created: 20210714 Date Completed: 20211004 Latest Revision: 20211004
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Update Code:
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20240105
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PubMed Central ID:
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PMC8288060
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DOI:
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10.1167/iovs.62.9.21
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PMID:
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34259818
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Purpose: The purpose of this study was to evaluate the role of the canonical Wnt signaling in the development of the myopia.
Methods: Plasma from adult patients with myopia, myopic animal models including the adenomatous polyposis coli (APC) gene mutation mouse model, and the form deprivation (FD) induced mouse model of myopia were used. Niclosamide, a canonical Wnt pathway inhibitor, was orally administrated in animal models. Plasma levels of DKK-1 were determined by using enzyme-linked immunosorbent assay. Refraction, vitreous chamber depth (VCD), axial length (AL), and other parameters, were measured at the end of the FD treatment. Canonical Wnt signaling changes were evaluated by Western blot analysis and immunostaining analysis.
Results: Plasma level of Wnt inhibitor DKK-1 was markedly decreased in patients with myopia. Meanwhile, the canonical Wnt pathway was progressively activated during myopia development in mice. Moreover, inhibition of canonical Wnt signaling by niclosamide in mouse models markedly reduced lens thickness (LT), VCD, and AL elongation, resulting in myopia inhibition.
Conclusions: Dysregulation of canonical Wnt signaling is a characteristic of myopia and targeting Wnt signaling pathways has potential as a therapeutic strategy for myopia.
