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A. Otani, M. Sasahara, Y. Yodoi, T. Kameda, H. Kojima, A. Oishi, N. Yoshimura; Functional Recovery of Impaired Bone Marrow(BM)-Derived Myeloid Progenitor Cells as a New Therapeutic Strategy for Choroidal Neovascularization(CNV). Invest. Ophthalmol. Vis. Sci. 2008;49(13):4387.
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We have previously revealed that the functional impairment of circulating BM-derived progenitor cells was related to the bilateral wet-AMD and large CNV formation of AMD patients (Yodoi et al. IOVS, 2007). This study is to investigate a significance of controlling BM-derived cells as a therapeutic strategy for wet-AMD.
Laser-induced mice choroidal neovascularization (CNV) model was made after BM transplantation. Aged female C57BL/6 mice (over 40 weeks old) were used as recipient mice for BM transplantation. The BM was obtained from young female (8 weeks old) and aged female (over 40 weeks old) C57BL/6 mice. Quantitative analysis of CNV was done with paraffin embedded section by measuring the diameter, maximum thickness, and the area of CNV using image analysis software. Colony forming units (CFU) were done using an established method and used as a functional measure of BM-derived cells. Characterization of BM-derived cells was done by flow cytometric analysis.
The function of BM-derived myeloid progenitors decreases with age. Young mice (<8w, n=6) had significantly higher CFU-GM (granulocyte macrophage) than aged mice (>40w, n=6, mean, 34.7±1.5 vs. 21.0±4.7, p=0.02). After BM-transplantation was done, the CFU-GM of young (<8w) BM transplanted aged mice (>40w) showed significant recovery compared to aged (>40w) BM transplanted aged mice (>40w) (29.4±2.8 vs. 11.7±3.4, p=0.002). Young control mice (8w) developed significantly smaller laser-induced CNV than aged mice (>40w). Aged mice that were reconstituted with young BM (>40w + 8w BM) had significantly smaller CNV compared to aged mice with aged bone marrow transplantation (>40w + >40w BM, p<0.02). Flow cytometric analysis of BM cells in young and aged mice showed no significant difference in the number of cells with stem or progenitor phenotypes.
Functional activation of BM-derived circulating myeloid progenitors can be a new therapeutic approach for wet AMD.
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