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Matilda F. Chan, Jing Li, Zena Werb; Macrophage Metalloelastase (MMP12) Regulates Inflammation and Neovascularization Following Corneal Injury. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3560.
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MMP12 (Macrophage Metalloelastase) is a protease expressed by macrophages, and corneal epithelial and stromal cells following injury. In this study, we examined the role of MMP12 in the regulation of inflammation and neovascularization following corneal stromal injury.
Alkaline burn injuries created by topical application of 0.1N NaOH were performed on corneas of WT and MMP12-/- mice. Uninjured corneas and corneas injured 6 days prior were fixed for whole mounts and confocal microscopy was performed for the detection of macrophages and corneal neovascularization. To assess the role of MMP12 produced by bone marrow-derived macrophages (BMDMs) on the regulation of corneal inflammation and neovascularization following injury, bone marrow transplantation was performed. Bone marrow cells from WT and MMP12-/- mice were reciprocally transplanted into recipient mice to generate bone marrow chimeric mice. Corneas of transplanted mice were then chemically injured 6 weeks later to ensure engraftment and collected 6 days later for histological analysis to evaluate macrophage accumulation and corneal neovascularization.
Chemically injured corneas of MMP12-/- mice demonstrated increased macrophage accumulation and neovascularization compared with injured corneas of WT mice. Following transplantation of WT and Mmp12-/- bone marrow cells into Mmp12-/- and WT recipient mice respectively, fewer macrophages were noted in the injured corneas of MMP12-/- recipient mice while similar neovascular lengths were observed in injured corneas of transplanted Mmp12-/- and WT recipient mice.
These findings demonstrate that MMP12 has a protective effect in response to corneal injury by negatively regulating macrophage accumulation and neovascularization. Corneal macrophage accumulation appears to be primarily regulated by MMP12 produced by BMDMs while corneal neovascularization is influenced by MMP12 produced by both corneal cells and BMDMs.
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