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C. Tsutsumi, K. Sonoda, T. Ishibashi; The Relative Contribution of Infiltrating Bone Marrow-Derived Cells in Developing Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3944.
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Purpose: Some investigators demonstrated that local inflammation contributed to choroidal neovascularization (CNV) formation. In fact, several populations of marrow-derived inflammatory cells were accumulated to the eye in human AMD patients. However, the dynamics and the relative contributions of each population have not studied in detail. The aim of this study is to elucidate the role of each infiltrating populations in developing CNV. Methods: Female 8-10 weeks C57BL/6 mice, CCR2 knockout (KO) mice and wild-type (WT) mice with same genetic background of KO were used. CCR2 KO mice were known to be impaired macrophage accumulation to the particular lesion. Experimental CNV was induced with rupturing in Bruch’s membrane by laser photocoagulation (PC). After PC, the kinetic of ocular-infiltrating inflammatory cells were analyzed by flow cytometry. Moreover, the neutrophils, NK cells and T lymphocytes were depleted by in vivo treatment with anti-mouse Gr-1 mAb, anti-asiaroGM1 Ab and the combination of anti-mouse CD4/CD8 mAbs, respectively. Seven days after PC, the eyes were enucleated and the areas of CNV were measured in the choroidal flat mounts. Results: Neutrophils increased peak at 24hr and macrophage peak at 48hr after PC. Infiltration of NK cells and T lymphocytes were begun to observe at 24 hr and gradually increased. B lymphocytes were not detected. The areas of CNV were markedly decreased in KO mice compared to WT mice. CNV areas were not significantly changed between non-depleted, neutrophil-depleted , NK cell-depleted and T cell-depleted C57BL/6 mice. However, the neutrophil-depleted KO mice significantly reduced CNV area compared to non-depleted KO mice. Conclusions: Macrophages was crucial for CNV formation mainly. Although NK cells and lymphocytes had little effect, neutrophils might partially contribute to CNV formation.
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