title: A murine model of contact lens-associated fusarium keratitis.
abstract: OBJECTIVE
  Fusarium solani and F. oxysporum were the causative organisms of the 2005/2006 outbreak of contact lens-associated fungal keratitis in the United States. The present study was an investigation of the ability of F. oxysporum grown as a biofilm on silicone hydrogel contact lenses to induce keratitis.
  
  
  METHODS
  A clinical isolate of F. oxysporum was grown as a biofilm on lotrafilcon A contact lenses, and a 2-mm diameter punch was placed on the abraded corneal epithelium of either untreated or cyclophosphamide-treated C57BL/6 mice or of IL-1R1(-/-), MyD88(-/-), TLR2(-/-), or TLR4(-/-) mice. After 2 hours, the lens was removed, and corneal opacification, colony forming units (CFUs), and histopathology were evaluated.
  
  
  RESULTS
  C57BL/6 mice developed severe corneal opacification within 24 hours and resolved after four days. In contrast, corneal opacification progressed in cyclophosphamide-treated mice, and was associated with unimpaired fungal growth in the cornea, and with hyphae penetrating into the anterior chamber. The phenotype of MyD88(-/-) and IL-1R(-/-) mice was similar to that of cyclophosphamide-treated animals, with significantly impaired cellular infiltration and fungal clearance. Although TLR4(-/-) mice developed a cellular infiltrate and corneal opacification similar to C57BL/6 mice, the CFU count was significantly and consistently higher.
  
  
  CONCLUSIONS
  Fusarium grown as a biofilm on silicone hydrogel contact lenses can induce keratitis on injured corneas, with disease severity and fungal killing dependent on the innate immune response, including IL-1R1, MyD88, and TLR4.
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: Jyotsna
authors.initials: J
authors.lastname: Chandra
authors.forename: Pranab
authors.initials: P
authors.lastname: Mukherjee
authors.forename: Loretta
authors.initials: L
authors.lastname: Szczotka-Flynn
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
authors.forename: Eric
authors.initials: E
authors.lastname: Pearlman
mesh_terms: D000818:Animals; D018441:Biofilms; D054360:Chemokine CXCL1 / Q000378:metabolism; D015169:Colony Count, Microbial; D003261:Contact Lenses / Q000382:microbiology*; D003318:Corneal Opacity / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003320:Corneal Ulcer / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015821:Eye Infections, Fungal / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005670:Fusarium / Q000502:physiology*; D020100:Hydrogels; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D009181:Mycoses / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012828:Silicones; D051197:Toll-Like Receptor 4 / Q000502:physiology; D005466:Fluorocarbons
chemical_list: D054360:Chemokine CXCL1; D003520:Cyclophosphamide; D020100:Hydrogels; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D012828:Silicones; D051197:Toll-Like Receptor 4; C507780:Myd88 protein, mouse; C493487:Tlr4 protein, mouse; C481129:lotrafilcon A; D005466:Fluorocarbons