4.6 Article

Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy

Journal

LABORATORY INVESTIGATION
Volume 92, Issue 1, Pages 91-101

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2011.141

Keywords

angiogenesis; chemokines; inflammation; ischemic retinopathy; macrophage/microglia

Funding

  1. Ministry of Education, Science, Sports and Culture, Japan

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Recent clinical observations have indicated that vascular endothelial growth factor (VEGF) is a key factor that stimulates the development of preretinal pathological neovascularization (NV). However, it has not been established how intraretinal physiological revascularization of hypoxic avascular areas is regulated. Our earlier study on the gene expression profile of hypoxic retinas in a mouse model of oxygen-induced retinopathy (OIR) showed that macrophage inflammatory protein-1 beta (MIP-1 beta) was the most upregulated protein. The purpose of this study was to investigate the role played by MIP-1 beta in recruiting bone marrow-derived monocyte lineage cells (BM-MLCs) in a mouse model of OIR. Our results showed that MIP-1 beta was upregulated, and its receptor, CCR5, was expressed in BM-MLCs in the hypoxic inner retina. Neutralizing Ab against MIP-1 beta reduced the infiltration of BM-MLCs into the OIR retinas and increased the avascular area and preretinal neovascular tufts. A very strong significant correlation was found between the area of the preretinal neovascular tufts and the avascular area, regardless of the extent of BM-MLC infiltration into the OIR retinas. Additional treatment with VEGF-A-neutralizing Ab showed that the MIP-1 beta-regulated pathological NV strongly depended on VEGF-A, which was probably secreted by the hypoxic avascular retinas. These results indicate that MIP-1 beta is involved in the recruitment of BM-MLCs, which have a significant role in the physiological revascularization of hypoxic avascular retinas. Overall, these findings indicate that the MIP-1 beta induction of BM-MLCs might possibly be used to promote intraretinal revascularization and thus prevent the abnormal NV in ischemic vision-threatening retinal diseases. Laboratory Investigation (2012) 92, 91-101; doi:10.1038/labinvest.2011.141; published online 12 September 2011

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