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Patrick M. Stuart, Megan Rogge, Xiao-Tang Yin; Soluble FasL therapy reduces Herpetic Stromal Keratitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4764.
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Fas ligand (FasL) is a death-inducing ligand that signals apoptosis in cells bearing the Fas protein, and plays a vital role in controlling the entrance of inflammatory cells and neovascularization of ocular tissue. We tested the ability of a soluble form of FasL (sFasL) to control Herpes Simplex Virus-1 (HSV-1)-induced corneal disease, Herpetic Stromal Keratitis (HSK).
We tested the therapeutic value of soluble FasL in both an acute and recurrent model of HSK using BALB/c and BALB-lpr mice. sFasL was administered in a topical ointment directly to the cornea every day after infection (acute disease) or reactivation (recurrent disease). sFasL treatment was augmented by subconjunctival injection every 3-5 days. The controls for this experiment included mice that were treated with ointment alone (puralube) or with ointment to which a soluble form of TRAIL (sTRAIL) was added and injection of sTRAIL. sTRAIL was used as a negative control because it is a soluble death factor that is normally released in the eye and induces apoptosis in primary tumor cell lines but is not thought to control ocular inflammation. These mice were evaluated for corneal disease by a masked observer who scored the corneas for opacity and neovascularization.
Following acute infection, wild-type (BALB/c) mice treated with sFasL displayed reduced incidence of opacity and neovascularization when compared to the sTRAIL and puralube groups post infection. As a negative control for sFasL treatment, BALB-lpr mice, which do not express functional Fas and thus are not susceptible to FasL-induced apoptosis, were also tested. Results showed no difference in HSK between sFasL and sTRAIL treated groups, as expected. When BALB/c mice undergoing recurrent HSK were treated with sFasL, we saw a decrease in both opacity and neovascularization as compared to the sTRAIL treated mice.
Mice infected with HSV-1 that are treated with an apoptotic form of sFasL display reduced incidence of acute and recurrent HSK. These data we believe are due to the apoptotic signaling by sFasL of the Fas molecule found on inflammatory cells and vascular endothelium of newly growing vessels which are attempting to invade the cornea following infection or reactivation.
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