Opposite Roles of CCR2 and CX3CR1 Macrophages in Alkali-induced Corneal Neovascularization

P.R. Lu, Lingling Li, G. Liu, N. van Rooijen, N. Mukaida

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Abstract

Purpose: The purpose of this study was to investigate the role of infiltrating macrophages in the development of experimental corneal neovascularization. Methods: Corneal neovascularization was induced by alkali injury in mice deficient in a macrophage-tropic chemokine receptor, CCR2 or CX3CR1, or in mice treated with clodronate-liposomes (Cl2MDP- lip), which can selectively deplete monocytes/macrophages. Corneal neovascularization 2 weeks after alkali injury was assessed by immunostaining with anti-CD31 antibody. Intracorneal expression of proangiogenic and antiangiogenic factors was determined by rev transcription-polymerase chain reaction. Results: CCR2-deficient mice exhibited reduced alkali-induce corneal neovascularization with reduced macrophage infiltration, whereas CX3CR1-deficient mice developed a more severe form of alkali-induced corneal neovascularization with reduced macrophage infiltration. Selective macrophage depletion by C12MDP-lip treatment failed to affect alkali-induced corneal neovascularization as evidenced by immunohistochemical analysis using anti-CD31 antibody, whereas intracorneal macrophage infiltration was markedly reduced. Alkali injury enhanced the expression of proangiogemc molecules, including matrix metalloproteinase-2, matrix metalloproteinase-9, and tumor necrosis factor alpha, and antiangiogenic factors, including a disintegrin and metal loprotease with thrombospondin (ADAMTS)-1, thrombospondin-1, and thrombospondin-2. C12MDP-lip-treated mice exhibited a reduction in the messenger RNA expression of these molecules. Conclusion: Because CCR2- and CX3CR1-expressing macrophages exhibit opposite activities in angiogenesis, depletion of macrophages as a whole may not have apparent effects on alkali-induced corneal neovascularization
Original languageUndefined/Unknown
Pages (from-to)562-569
JournalCornea
Volume28
Issue number5
DOIs
Publication statusPublished - 2009

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