Evaluation of susceptibility and innate immune response in C57BL/6 and BALB/C mice during candida albicans endophthalmitis

Abstract

PURPOSE. Candida remains the leading cause of fungal endophthalmitis. However, the pathobiology and innate immune responses in this disease are not well characterized. Here, we developed two murine models of candida endophthalmitis and evaluated their disease susceptibility and differential immune response. METHODS. Endophthalmitis was induced in C57BL/6 (B6) and BALB/c mice by intravitreal injection of Candida albicans (CA). Disease progression was monitored by slit-lamp examination and clinical scoring, followed by retinal function assessment using electroretinography (ERG). Enucleated eyes were used to estimate fungal burden and retinal tissue damage by hematoxylin and eosin and TUNEL staining. The level of inflammatory mediators were determined by quantitative Polymerase Chain Reaction (qPCR) and enzyme-linked immunosorbent assay, whereas neutrophil infiltration was assessed by flow cytometry and immunostaining. RESULTS. Intravitreal injection of CA at 6500 colony-forming units resulted in sustained (non-resolving) ocular inflammation in both B6 and BALB/c mice as evidenced by increased levels of inflammatory cytokines (tumor necrosis factor-a, interleukin-1β, and interleukin-6) and chemokine (CXCL2/MIP-2). In both mouse strains, fungal burden peaked at 24 to 48 hours post-infection (hpi) and decreased by 72 to 96 hpi. CA-infected eyes exhibited increased polymorphonuclear neutrophils (PMN) infiltration and retinal tissue damage. Overall retinal function declined rapidly, with a significant reduction in ERG response at 12 hpi and near-total loss by 24 hpi. Differential analyses revealed increased pathology in BALB/c versus B6 mice. CONCLUSIONS. C. albicans was able to cause endophthalmitis in mice. Although BALB/c mice were found to be more susceptible to CA endophthalmitis, both BALB/c and B6 models could be used to study fungal endophthalmitis and test therapeutic modalities.