RGD Reference Report - A murine model of contact lens-associated fusarium keratitis. - Rat Genome Database

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A murine model of contact lens-associated fusarium keratitis.

Authors: Sun, Y  Chandra, J  Mukherjee, P  Szczotka-Flynn, L  Ghannoum, MA  Pearlman, E 
Citation: Sun Y, etal., Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1511-6. doi: 10.1167/iovs.09-4237. Epub 2009 Oct 29.
RGD ID: 7794845
Pubmed: PMID:19875664   (View Abstract at PubMed)
PMCID: PMC2868423   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.09-4237   (Journal Full-text)

PURPOSE: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
keratitis  ISOTlr4 (Mus musculus)7794845; 7794845associated with Eye Infections and FungalRGD 
keratitis  IMP 7794845associated with Eye Infections and FungalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr4  (toll-like receptor 4)

Genes (Mus musculus)
Tlr4  (toll-like receptor 4)

Genes (Homo sapiens)
TLR4  (toll like receptor 4)


Additional Information