Abstract
Purpose: :
Fusarium species were identified as the cause of the contact lens â€" related fungal keratitis in 2005/2006, and are also an important cause of microbial keratitis worldwide. We recently showed that Fusarium generate a biofilm when cultured on silicon hydrogel contact lenses1. In the current study, we examine the outcome of Fusarium biofilm exposed to the corneal surface and characterize the host innate immune pathways that regulate the outcome.
Methods: :
A of Fusarium were grown as biofilm on Lotrafilcon A contact lenses, and a 2mm diameter punch from lens containing biofilm was placed on abraded corneal epithelium of C57BL/6, TLR4-/- and IL-1R-/- and MyD88-/-mice. After 2h, the lens was removed, and corneal opacity, cellular infiltration and CFU were examined.
Results: :
Fusarium hyphae present in the biofilm rapidly penetrated the corneal stroma, and by 24h had entered the anterior chamber in all mouse strains. C57BL/6 mice showed an intense corneal infiltrate, and cleared the organism within 72h. In contrast, MyD88-/- and IL-1R-/- mice had impaired cellular infiltration and increased CFU. TLR4-/- mice had an intense cellular infiltrate, but CFU was elevated at 24h and 48h compared with C57BL/6 mice.
Conclusions: :
Fusarium as biofilm on contact lenses can induce severe keratitis. However, cellular infiltration and fungal killing is dependent on IL-1R1 and MyD88, whereas TLR4 regulates only fungal killing, possibly due to activation on infiltrating neutrophils.1Imamura et al. Antimicrobial Agents and Chemotherapy, 2008.This research was funded by NIH grants RO1EY14362 (EP) and P30EY11373 (EP), and with support from The Research to Prevent Blindness Foundation and the Ohio Lions Eye Research Foundation
Keywords: fungal disease • cornea: epithelium • contact lens