title: Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118).
abstract: OBJECTIVE
  Sterile corneal infiltrates can cause pain, blurred vision, and ocular discomfort in silicone hydrogel contact-lens users. The current study investigates the potential for the synthetic lymphocyte functional antigen-1 (LFA-1) antagonist lifitegrast (SAR 1118) to block corneal inflammation using a murine model.
  
  
  METHODS
  The role of LFA-1 (CD11a/CD18) was examined either in CD18(-/-) mice, by intraperitoneal injection of anti-CD11a, or by topical application of lifitegrast. Corneal inflammation was induced by epithelial abrasion and exposure to either tobramycin-killed Pseudomonas aeruginosa or Staphylococcus aureus in the presence of a 2-mm-diameter punch from a silicone hydrogel contact lens. After 24 h, corneal thickness and haze were examined by in vivo confocal microscopy, and neutrophil recruitment to the corneal stroma was detected by immunohistochemistry.
  
  
  RESULTS
  Neutrophil recruitment to the corneal stroma and development of stromal haze were significantly impaired in CD18(-/-) mice or after injection of anti-CD11a. Topical lifitegrast also inhibited P. aeruginosa- and S. aureus-induced inflammation, with the optimal application being a 1% solution applied either 2 or 3 times prior.
  
  
  CONCLUSIONS
  As LFA-1-dependent neutrophil recruitment to the corneal stroma can be blocked by topical lifitegrast, this reagent could be used in combination with antibiotics to prevent leukocyte infiltration to the corneal stroma in association with contact-lens wear.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Gadek
authors.forename: Charles A
authors.initials: CA
authors.lastname: O'Neill
authors.forename: Eric
authors.initials: E
authors.lastname: Pearlman
mesh_terms: D000818:Animals; D040881:CD11a Antigen / Q000276:immunology; D018821:CD18 Antigens / Q000235:genetics; D003261:Contact Lenses / Q000009:adverse effects; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D003319:Corneal Stroma / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D015818:Eye Infections, Bacterial / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020556:Neutrophil Infiltration / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D013203:Staphylococcal Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000302:isolation & purification; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D040881:CD11a Antigen; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D013450:Sulfones; C575157:lifitegrast; D010649:Phenylalanine