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D. Bauer, S. Wasmuth, H. Li, P. Hermans, N. van Rooijen, K.–P. Steuhl, A. Heiligenhaus; Function of Corneal Macrophages after Amniotic Membrane Transplantation in Mice with Herpes Stromal Keratitis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1632.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Macrophages enhance T cell–mediated immune response and thereby increase the severity of stromal keratitis (HSK) after corneal HSV–1 infection. After amniotic membrane transplantation (AMT), rapid improvement of HSK occurs, whereby T cells and neutrophils in the cornea are rapidely diminished. In this study we determined the functions of macrophages in the cornea with HSK following AMT. Methods:BALB/c mice were infected with 105 PFU of HSV–1 (KOS). Animals that had developed severe HSK on day 14 post infection were covered with AMT or tarsorrhapy for 1 day. In some of the mice, macrophages were depleted by subconjunctival injections of clodronat liposomes (Cl2MDP–LIP). Inflammatory cells in the cornea were studied by histology and electron microscopy. Expression of TNF–α, IL–12, IL–6, KC, and MIP–2 in the cornea were analyzed by ELISA. Neutrophils were cultured with or without AM and the numbers of apoptotic cells were determined by hoechst–staining. Results:Neutrophil apoptosis was induced when cocultivated with AM. The percentage of apoptotic neutrophils in the corneas was increased and macrophages occured early after AMT. TNF–α, IL–12, IL–6 and KC content in the cornea were decreased in the AMT group, while MIP–2 expression was increased. Animals with AMT and Cl2MDP–LIP showed increased numbers of and apoptotic PMNs and cell debris compared to PBS–LIP group. Conclusions:These findings show that rapid healing of HSK after AMT correlates with increased expression of chemotactic factors and macrophage infiltration in the cornea. During the healing phase of HSK after AMT macrophages are critical for phagocytosis of cell debris and apoptotic neutrophils.
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