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V.L. Perez, M. Gregory, A. Marshak-Rothstein, B. Ksander; Expression of Soluble Fas Ligand in the Cornea Inhibits Lipopolysaccharide Induced Keratitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):698.
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Purpose: We have previously shown that the selective expression of soluble Fas Ligand (sFasL) in the cornea does not induce inflammation and blocks the activation of neutrophils. We hypothesize that sFasL effectively blocks the development of innate immunity and therefore will prevent destructive corneal inflammation associated with keratitis. To test this we examined the effects of sFasL in a model of lipopolysaccharide (LPS) induced keratitis. Methods: sFasL was expressed in the corneal stroma of C57BL/6 mice by adenoviral transduction, using intra-stromal injection of adenoviral vectors. The adenoviral vector contained a gene encoding the soluble-only form of FasL and a GFP marker gene, both under the control of a CMV promoter. Gene expression was confirmed by measuring GFP expression in the cornea with fluorescent microscopy and by western blot. To induce keratitis, LPS intrastromal injections (4ug) were performed 24 hrs after gene transduction and corneal inflammation was monitored by slit-lamp examination and histological analysis. Results: Intra-stromal injection of sFasL or control vector alone resulted in GFP expression for 30 days, without any evidence of inflammation. Intra-stromal injection of LPS into corneas transduced with the control adenoviral vector developed keratitis at 3-5 days, followed by corneal scarring and neovascularization after 10 days. By contrast, corneal expression of sFasL effectively prevented LPS induced corneal keratitis, scaring, and neovascularization. Histological analysis of corneas with LPS induced keratitis revealed a vigorous infiltration of neutrophils, which was reduced in corneas treated with sFasL. Conclusion: Corneas expressing sFasL are protected against LPS induced inflammation and scarring. This is the first demonstration of the role of sFasL in regulating in vivo innate immune responses in a model of inflammation induced by LPS signaling. Furthermore, it suggests the potential use of sFasL in treating neutrophil mediated keratitis.
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