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Yong Yuan, Liyun Zhang, Fei Dong, Yujin Zhang, Mindy Call, Chia-yang Liu, Winston Kao; Activation of Noncanonical Wnt Signaling Elicits Glaucoma in Mice. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3677.
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Inhibition of the Wnt signaling pathway has been implicated in the pathogenesis of primary open-angle glaucoma (POAG), but the underlying mechanism remains unclear. We reported that dexamethasone (DEX), a glaucoma-inducing drug, induces glaucomatous cytoskeleton re-arrangement through noncanonical Wnt signaling in cultured trabecular meshwork cells, suggesting the potential role of noncanonical Wnt signaling in POAG pathogenesis. Here, efforts were made to demonstrate that ocular gene transfer of the noncanonical Wnt ligand, Wnt5a, can elicit glaucoma in mice.
Recombinant adenovirus (AdWnt5a) was injected into the anterior chamber of mice. Intraocular pressure (IOP) was measured by non-invasive tonometer. The enucleated eyes of the experimental mice were subjected to histopathology and immunohistochemistry analysis.
Gene transfer of Wnt5a into the anterior chamber resulted in elevated IOP which is accompanied by the activation of retinal glial cells and the loss of retinal ganglion cells. Noncanonical Wnt signaling is also activated in the trabecular meshwork as revealed by phosphorylated myosin light chain immunostaining.
Our data demonstrates that the noncanonical Wnt ligand, Wnt5a, elicits glaucoma when over-expressed in the mouse anterior chamber. This finding lends support to the hypothesis that noncanonical Wnt signaling plays an important role in glaucoma pathogenesis.
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