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A. A. Kramerov, N. Sengupta, S. Caballero, A. Afzal, L. C. Shaw, L. A. Pinna, M. B. Grant, A. V. Ljubimov; Inhibition of Protein Kinase CK2 Blocks Endothelial Precursor Cell Incorporation into Neovascular Tufts in Mouse Oxygen-Induced Retinopathy Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4101.
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Protein kinase CK2 is highly expressed in retinal astrocytes and is important for retinal neovascularization in the mouse oxygen-induced retinopathy (OIR). The purpose was to examine the effects of CK2 inhibition on the incorporation of bone marrow-derived endothelial progenitor cells (EPC) into sites of retinal neovascularization in OIR.
8-day old C57BL mouse pups received one intravitreal injection into the right eye of 5,000 Ska-1- and c-kit-positive bone marrow-derived EPC from green fluorescent protein (gfp) transgenic mice. Left eye was left as a control. On days 12 to 17, pups received intraperitoneal injections of a specific CK2 inhibitor, 4,5,6,7-tetrabromobenzotriazole (TBB) twice daily at 100 mg/g/day or vehicle (20% PEG 400 + 2% Tween-80, pH 7.4). On day 17, animals were sacrificed, retinas perfused with rhodamine-dextran and flat mounts analyzed by confocal microscopy. Some eyes were fresh-frozen and cryostat sections examined by immunohistochemistry.
At day 17, distinct retinal neovascularization developed. In EPC-injected eyes gfp+ cells incorporated into neovascular tufts. Noninjected contralateral eyes had no fluorescent cells present. Labeled EPC showed similar distribution in retinas from untreated and vehicle-treated animals. In contrast, retinas from TBB-treated animals demonstrated a significant decrease of gfp+ cells including areas of retinal neovascularization. Flat mounts data were confirmed on cryostat sections using antibody to gfp.
The data show that EPC participate in pathologic retinal neovascularization in the OIR model by incorporating into neovascular tufts. Marked inhibition of this process by a specific CK2 blocker suggests a distinct mechanism of CK2 participation in angiogenesis by facilitating EPC incorporation into retinal neovessels, possibly by stimulating cell migration and proliferation.
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