Research Of Experimental Candidaalbicans Keratitis In Different Strain Mouse

ObjectivePathogenesis of fungal keratitis remains largely unclear. This study was to nvestigatethe role of genetic background in determining the development or prognosis of theexperimental fungal keratitis by comparing the disease courses and related molecules ofexperimental Candida albicans in two common mouse strains.MethodsIntrastromal inoculation of1x105Candida albicans blastospores into corneas of Balb/c andC57BL/6mice made all mice develop typical keratitis. The diseases were monitored using slit lampmicroscope and scored for comparison of symptoms. At desired time points, blood was collectedand corneal homogenate were prepared for ELISA measurement of IFNγ or IL17, and othercorneas were processed for histology evaluation, pathogen load measurement or total RNAextraction, later of which was subjected to reverse transcription in conjunction with real-timepolymerase chain reaction to measure the interested genes like collagens, matrix metalloproteinases(MMPs) and their tissue inhibitors (TIMPs.)ResultsThe infected corneas from the two strains presented different manifestations. Cornealtransparency was less affected in Balb/c mice than in C57BL/6mice, and Balb/c corneas containedless pathogens than C57BL/6corneas during the measured period (10days). Keratitis in bothstrains started to resolve around days7~10but C57BL/6mice healed slower than Balb/c mice asindicated by disease presentation, histology and pathogen burden assay. By day7post infection,pseudohyphae were rare but cellular infiltration remained intensive in both strains. The surface ofthe Balb/c corneas remained relatively intact and smooth, and C57BL/6corneal lesions producedopen erosion areas but perforation was never seen in current study. In both sera and corneas, IL17expression increased up-regulated earlier than IFNγ, and C57BL/6mice produced higher IL17levels and lower IFNγ levels than Balb/c mice. Compared with C57BL/6mice, Balb/c corneasproduced more MMP-2, col3a1and col4a1, less or equivalent TIMP-2at all detected time points, or more MMP-13, less MMP-8, MMP-9and TIMP-1at day3post infection, but less MMP-13,basically equivalent MMP-8and more MMP-9at later time points.ConclusionsThe disease courses of experimental Candida albicans keratitis depend on geneticbackground of host animals. The balance between IL17and IFNγ, as well as among the commoninjury-and wound healing-related proteins may contribute to the pathogenesis of Candida albicanskeratitis. The significance and limitation of this observation is discussed.