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.
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.
Authors: Shamila Khan; Nerida Cole; Emma B Hume; Linda Garthwaite; Timothy C R Conibear; David H Miles; Yulina Aliwaga; Mark B Krockenberger; Mark D P Willcox Journal: J Leukoc Biol Date: 2006-10-06 Impact factor: 4.962
Authors: Douglas C Chang; Gavin B Grant; Kerry O'Donnell; Kathleen A Wannemuehler; Judith Noble-Wang; Carol Y Rao; Lara M Jacobson; Claudia S Crowell; Rodlescia S Sneed; Felicia M T Lewis; Joshua K Schaffzin; Marion A Kainer; Carol A Genese; Eduardo C Alfonso; Dan B Jones; Arjun Srinivasan; Scott K Fridkin; Benjamin J Park Journal: JAMA Date: 2006-08-23 Impact factor: 56.272
Authors: Kathrin Luther; Antonella Torosantucci; Axel A Brakhage; Jürgen Heesemann; Frank Ebel Journal: Cell Microbiol Date: 2006-08-31 Impact factor: 3.715
Authors: M Jayahar Bharathi; R Ramakrishnan; R Meenakshi; S Padmavathy; C Shivakumar; M Srinivasan Journal: Ophthalmic Epidemiol Date: 2007 Mar-Apr Impact factor: 1.648
Authors: Seang-Mei Saw; Peng-Lim Ooi; Donald T H Tan; Wei-Boon Khor; Chee-Weng Fong; Jayne Lim; Howard Y Cajucom-Uy; Derrick Heng; Suok-Kai Chew; Tin Aung; Ai-Ling Tan; Cheng-Leng Chan; Steven Ting; Paul A Tambyah; Tien-Yin Wong Journal: Arch Ophthalmol Date: 2007-05
Authors: Madhu Dyavaiah; Rama Ramani; David S Chu; David C Ritterband; Mahendra K Shah; William A Samsonoff; Sudha Chaturvedi; Vishnu Chaturvedi Journal: BMC Ophthalmol Date: 2007-01-30 Impact factor: 2.209
Authors: Pranab K Mukherjee; Jyotsna Chandra; Changping Yu; Yan Sun; Eric Pearlman; Mahmoud A Ghannoum Journal: Invest Ophthalmol Vis Sci Date: 2012-07-03 Impact factor: 4.799