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(Journal of Leukocyte Biology. 2003;73:137-144.)
© 2003 by Society for Leukocyte Biology

Role of MCP-1 and MIP-1{alpha} in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization

Shigeo Yoshida*, Ayako Yoshida*, Tatsuro Ishibashi*, Susan G. Elner{dagger} and Victor M. Elner{dagger}

* Department of Ophthalmology, Kyushu University Graduate School of Medicine, Fukuoka, Japan; and
{dagger} Department of Ophthalmology & Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor

Correspondence: Shigeo Yoshida, M.D., Ph.D., Department of Ophthalmology, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. E-mail: usyosi{at}yahoo.com

Macrophages are important participants in neovascularization. This study was designed to examine the role of the monocyte/macrophage chemotactic proteins, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1{alpha} (MIP-1{alpha}) in a mouse model of oxygen-induced ischemic retinopathy and to determine whether the morphology and distribution of macrophages/microglia are concomitantly altered. The MCP-1, MIP-1{alpha} mRNA levels increased at 3 h after ischemia. MCP-1, MIP-1{alpha}, and vascular endothelial growth factor protein levels were also increased markedly and were maximal on days 1, 0.5, and 1, respectively, after ischemia. In situ hybridization showed that MCP-1 and MIP-1{alpha} were localized in the hypoxic inner retina. Immunostaining demonstrated that the macrophages/microglia in the retina had morphological changes with enlarged processes, and some were closely associated with neovascular tufts at postnatal day 17. Coadministration of the neutralizing antibodies against MCP-1 and MIP-1{alpha} inhibited retinal neovascularization by 30%. Our data suggest that MCP-1 and MIP-1{alpha} are involved in the induction of retinal neovascularization and play a role in the inflammation induced by the ischemic retinopathy, possibly by modulating or attracting macrophages/microglia.

Key Words: cytokines • macrophages • retinal ischemia • angiogenesis




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