Abstract
Abstract: :
Purpose: To establish a murine model of corneal fusariosis that permits mycological and histopathological evaluation of fungal infection and pathogenesis. Methods: Corneas of immunocompetent and cyclophosphamide–treated adult BALB/c mice were topically inoculated with Fusarium solani following corneal scarification. Mock–inoculated eyes served as controls. Eyes were scored daily for 8 days and at 2 weeks post infection (p.i.) using a 12–point scale to categorize corneal involvement. Eyes were enucleated for quantitative fungal recovery at 6 hours, 1 day, 4 days, 8 days and 14 days p.i. and at 1 day, 4 days, and 8 days p.i. for histopathological examination. Results: A dose–dependent response was observed in cyclophosphamide–treated mice with 1x103 culturable units (CU) of F. solani causing mild corneal disease and moderate to severe keratitis being consistently induced with >1x104 CU. Fungi were recovered from the infected eyes by quantitative microbial culturing. Treatment with cyclophosphamide increased disease severity compared to immunocompetent mice and delayed fungal clearance from ocular tissues. Fungal hyphae, inflammatory cells, and stromal necrosis were histologically evident within corneal tissue and correlated with disease severity. Hyphae invaded the anterior two thirds of the cornea in cyclophosphamide–treated animals within one day and reached Descemet’s membrane by 4 days post infection. Conclusions: Although the normal mouse cornea resists fungal infection, F. solani keratitis can be induced in immunocompromised mice following surface scarification. Topical application of F. solani in cyclophosphamide–treated animals resulted in infection and clinical disease that could be evaluated both in vivo and following removal of the ocular tissue. This new animal model for Fusarium keratomycosis will allow experimental studies on the pathogenic mechanisms of fungal eye disease.
Keywords: fungal disease • keratitis • microbial pathogenesis: experimental studies