title: Therapeutic Use of Soluble Fas Ligand Ameliorates Acute and Recurrent Herpetic Stromal Keratitis in Mice.
abstract: OBJECTIVE
  The present study was designed to test the therapeutic value of soluble FasL (sFasL) in an acute model of herpetic stromal keratitis (HSK) and, more importantly, a recurrent model of HSK using BALB/c, BALB-lpr, and National Institutes of Health (NIH) mice.
  
  
  METHODS
  Mice were infected either acutely with the KOS strain of herpes simplex virus 1 (HSV-1) or latently with the McKrae strain of HSV-1. Acutely infected mice as well as ultraviolet-B (UV-B) reactivated mice (recurrent infection) were treated with sFasL, or soluble TNF-related apoptosis inducing ligand (sTRAIL), or BSA daily or 3 times/wk by using either a combination of subconjunctival injection and topical ointment, or with topical ointment alone. These mice then were evaluated for corneal opacity and neovascularization for 6 weeks.
  
  
  RESULTS
  Following acute and recurrent HSV-1 infection, wild-type BALB/c mice treated with sFasL displayed significantly reduced incidence of corneal opacity and neovascularization compared to the control animals. However, BALB-lpr mice, which are deficient in Fas+ inflammatory cells, displayed no such differences in ocular disease, as expected. Latently infected NIH mice treated with sFasL displayed similar results. Flow cytometric analysis revealed that the corneal inflammatory infiltrate in those treated with sFasL was significantly less than in sTRAIL- or BSA-treated mice. Furthermore, corneas from sFasL-treated mice displayed relatively more cells undergoing apoptosis.
  
  
  CONCLUSIONS
  This study provides evidence that sFasL treatment has potential therapeutic benefit in reducing inflammatory infiltrate and neovascularization in primary and recurrent forms of HSK, and that it does so by augmenting the restriction of Fas+ inflammatory cells mediated by membrane FasL.
authors.forename: Megan
authors.initials: M
authors.lastname: Rogge
authors.forename: Xiao-Tang
authors.initials: XT
authors.lastname: Yin
authors.forename: Lisa
authors.initials: L
authors.lastname: Godfrey
authors.forename: Priya
authors.initials: P
authors.lastname: Lakireddy
authors.forename: Chloe A
authors.initials: CA
authors.lastname: Potter
authors.forename: Chelsea R
authors.initials: CR
authors.lastname: Del Rosso
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Stuart
mesh_terms: D000208:Acute Disease; D000818:Animals; D003319:Corneal Stroma / Q000187:drug effects / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000494:pharmacology*; D018259:Herpesvirus 1, Human; D016849:Keratitis, Herpetic / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012008:Recurrence
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein