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Kimio Takeuchi, Mitsuru Nakazawa, Yuichi Ebina; Effects of Trehalose on VEGF-Stimulated Angiogenesis and Myofibroblast Proliferation: Implications for Glaucoma Filtration Surgery. Invest. Ophthalmol. Vis. Sci. 2011;52(9):6987-6993. doi: 10.1167/iovs.11-7478.
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To investigate whether trehalose inhibits VEGF-stimulated or inflammatory angiogenesis and the proliferation of myofibroblasts.
Normal human dermal fibroblasts and human umbilical vein endothelial cells (HUVECs)were cocultured in trehalose-containing medium (2.5/5.0/7.5/10.0%) with or without VEGF (10 ng/mL). After 11 days, the area, length, joint, and path of neovascularization were evaluated. The effect of topical trehalose on corneal neovascularization was examined in vivo by treating Balb/c mice with alkali burn-induced corneal neovascularization. After 14 days of trehalose treatment, corneal vessels were visualized in flatmounts. The expressions of VEGFR2, phospho-VEGFR2, and vimentin were observed. Then a separate coculture model of the myofibroblasts and HUVECs was used to observe the morphologic changes of the myofibroblasts by trehalose. Furthermore, myofibroblasts were cultured with trehalose to examine the cytokeratin and E-cadherin expressions.
In the in vitro models, there was a significant trehalose dose-dependent inhibition of neovascularization. In the in vivo alkali burn models, corneal neovascularization was significantly inhibited by treatments using ≥2.5% trehalose eyedrops. The expressions of VEGFR2, phospho-VEGFR2, and vimentin were downregulated by trehalose. When trehalose was added to the medium, the myofibroblasts were transformed into epithelial cell-like cells. The transformed myofibroblasts expressed cytokeratin but not E-cadherin.
Trehalose prevents angiogenesis by partially downregulating VEGFR2 expression. In addition, trehalose inhibits the proliferation of myofibroblasts partially by inducing mesenchymal-epithelial transition. These findings suggest that trehalose has potential for use as a new agent that can control angiogenesis and fibrosis and potential for use in glaucoma surgery.
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