PURPOSE: Endothelial progenitor cells (EPC) have been shown to participate in ischemia-induced retinal neovascularization (NV). Overactivation of Wnt signaling has a pathogenic role in ischemia-induced retinal NV. The purpose of this study is to determine whether Wnt signaling regulates EPC release. METHODS: Oxygen-induced retinopathy (OIR) was used as a model of retinal NV and Wnt pathway activation. The EPC, marked as c-Kit(+)/Tie-2(+) cells in the peripheral blood and bone marrow, were quantified using flow cytometry following immunolabeling. The Wnt signaling activity was evaluated by measuring nonphosphorylated β-catenin levels and X-gal staining in the Wnt reporter mice (Bat-gal mice). RESULTS: The c-Kit(+)/Tie-2(+) cells were increased significantly in the peripheral blood and bone marrow of mice with OIR, compared to non-OIR mice. Overexpression of kallistatin, an endogenous inhibitor of the Wnt pathway, in kallistatin transgenic (kallistatin-TG) mice with OIR attenuated the increases of c-Kit(+)/Tie-2(+) cells in the peripheral blood and bone marrow, compared to WT mice with OIR. When the Bat-gal mice were crossed with kallistatin-TG mice, kallistatin overexpression suppressed the OIR-induced increases of X-gal-positive cells in the retinas and bone marrow, suggesting inhibition of Wnt signaling in these tissues. Furthermore, intraperitoneal injection of LiCl, a Wnt signaling activator, increased c-Kit(+)/Tie-2(+) cells in the peripheral blood of normal mice. Consistently, LiCl activated Wnt signaling in the retina and bone marrow cells in Bat-gal mice. CONCLUSIONS: The Wnt signaling pathway has an important role in EPC release during retinal NV in OIR.
PURPOSE: Endothelial progenitor cells (EPC) have been shown to participate in ischemia-induced retinal neovascularization (NV). Overactivation of Wnt signaling has a pathogenic role in ischemia-induced retinal NV. The purpose of this study is to determine whether Wnt signaling regulates EPC release. METHODS:Oxygen-induced retinopathy (OIR) was used as a model of retinal NV and Wnt pathway activation. The EPC, marked as c-Kit(+)/Tie-2(+) cells in the peripheral blood and bone marrow, were quantified using flow cytometry following immunolabeling. The Wnt signaling activity was evaluated by measuring nonphosphorylated β-catenin levels and X-gal staining in the Wnt reporter mice (Bat-gal mice). RESULTS: The c-Kit(+)/Tie-2(+) cells were increased significantly in the peripheral blood and bone marrow of mice with OIR, compared to non-OIR mice. Overexpression of kallistatin, an endogenous inhibitor of the Wnt pathway, in kallistatin transgenic (kallistatin-TG) mice with OIR attenuated the increases of c-Kit(+)/Tie-2(+) cells in the peripheral blood and bone marrow, compared to WT mice with OIR. When the Bat-gal mice were crossed with kallistatin-TG mice, kallistatin overexpression suppressed the OIR-induced increases of X-gal-positive cells in the retinas and bone marrow, suggesting inhibition of Wnt signaling in these tissues. Furthermore, intraperitoneal injection of LiCl, a Wnt signaling activator, increased c-Kit(+)/Tie-2(+) cells in the peripheral blood of normal mice. Consistently, LiCl activated Wnt signaling in the retina and bone marrow cells in Bat-gal mice. CONCLUSIONS: The Wnt signaling pathway has an important role in EPC release during retinal NV in OIR.
Entities:
Keywords:
EPC; Wnt; bone marrow; peripheral blood; retina
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