Opposite roles of CCR2 and CX3CR1 macrophages in alkali-induced corneal neovascularization

• Published in: Cornea Vol. 28; no. 5; p. 562
• Main Authors: Lu, Peirong, Li, Longbiao, Liu, Gaoqin, van Rooijen, Nico, Mukaida, Naofumi, Zhang, Xueguang
• Format: Journal Article
• Language: English
• Published: United States 01.06.2009
• Subjects: Alkalies; Animals; Burns, Chemical - pathology; Clodronic Acid - administration & dosage; Cornea - metabolism; Cornea - pathology; Corneal Injuries; Corneal Neovascularization - chemically induced; Corneal Neovascularization - metabolism; Corneal Neovascularization - pathology; CX3C Chemokine Receptor 1; Down-Regulation; Eye Burns - pathology; Liposomes; Macrophages - drug effects; Macrophages - metabolism; Macrophages - pathology; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Knockout; Receptors, CCR2 - deficiency; Receptors, CCR2 - metabolism; Receptors, Chemokine - deficiency; Receptors, Chemokine - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1536-4798
• DOI: 10.1097/ico.0b013e3181930bcd

The purpose of this study was to investigate the role of infiltrating macrophages in the development of experimental corneal neovascularization. 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 reverse transcription-polymerase chain reaction. CCR2-deficient mice exhibited reduced alkali-induced 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 Cl2MDP-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 proangiogenic molecules, including matrix metalloproteinase-2, matrix metalloproteinase-9, and tumor necrosis factor alpha, and antiangiogenic factors, including a disintegrin and metalloprotease with thrombospondin (ADAMTS)-1, thrombospondin-1, and thrombospondin-2. Cl2MDP-lip-treated mice exhibited a reduction in the messenger RNA expression of these molecules. 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.