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A murine model of contact lens-associated fusarium keratitis
Yan Sun1, Jyotsna Chandra, Pranab Mukherjee
1Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
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.
Insights
Fusarium oxysporum biofilms on contact lenses cause fungal keratitis in mice. The severity of infection depends on the host's innate immune response, highlighting the role of IL-1R1, MyD88, and TLR4 in combating fungal keratitis.
Area of Science:
- Ophthalmology
- Mycology
- Immunology
Background:
- Contact lens-associated fungal keratitis is a serious ocular infection.
- Fusarium species, including Fusarium oxysporum, were identified as key pathogens in a significant outbreak.
- Understanding the pathogenesis of fungal keratitis induced by Fusarium biofilms on contact lenses is crucial for prevention and treatment.
Purpose of the Study:
- To investigate the capacity of Fusarium oxysporum, grown as a biofilm on silicone hydrogel contact lenses, to induce keratitis.
- To evaluate the role of the host's innate immune system in controlling Fusarium-induced keratitis.
Main Methods:
- A clinical isolate of Fusarium oxysporum was cultured as a biofilm on lotrafilcon A contact lenses.
- The lenses were applied to the abraded corneas of various mouse models, including immunocompetent, immunosuppressed, and knockout mice (IL-1R1-/-, MyD88-/-, TLR2-/-, TLR4-/-).
- Corneal opacification, fungal burden (colony-forming units), and histopathology were assessed post-infection.
Main Results:
- Fusarium biofilms on contact lenses induced severe keratitis in immunocompetent mice, characterized by corneal opacification.
- Immunosuppressed mice exhibited progressive keratitis with extensive fungal growth and anterior chamber invasion.
- Mice deficient in IL-1R1 or MyD88 showed impaired fungal clearance and reduced immune cell infiltration, similar to immunosuppressed animals.
- TLR4-deficient mice had similar opacification but higher fungal loads compared to controls, indicating a partially protective role of TLR4.
Conclusions:
- Fusarium biofilms on silicone hydrogel contact lenses can cause keratitis in injured corneas.
- The severity of fungal keratitis and the host's ability to clear the fungus are significantly influenced by the innate immune response.
- Key components of the innate immune system, including IL-1R1, MyD88, and TLR4, play critical roles in controlling Fusarium keratitis.
