Role of MCP-1 and MIP-1alpha in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization.
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-1alpha (MIP-1alpha) 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-1alpha mRNA levels increased at 3 h after ischemia. MCP-1, MIP-1alpha, 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-1alpha 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-1alpha inhibited retinal neovascularization by 30%. Our data suggest that MCP-1 and MIP-1alpha 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.
Yoshida
Shigeo
S
Department of Ophthalmology, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. usyosi@yahoo.com
Yoshida
Ayako
A
Ishibashi
Tatsuro
T
Elner
Susan G
SG
Elner
Victor M
VM
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018496:Hyperoxia; D007511:Ischemia / Q000209:etiology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D015861:Retinal Neovascularization / Q000209:etiology* / Q000473:pathology; D012173:Retinitis / Q000209:etiology / Q000473:pathology*
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger