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Bruce Glenn Rottmann, Pawan Kumar Singh, Ashok Kumar; Retinal Innate Response to Candida albicans in Exogenous Fungal Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5787.
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Among the fungal pathogens, Candida (C.) albicans is a major cause of fungal endophthalmitis. The purpose of this study is to develop a mouse model of C. albicans endophthalmitis and determine the innate immune response in this disease.
Exogenous C. albicans endophthalmitis was experimentally induced in eyes of C57BL/6 and BALB/c mice by intravitreal injection of a standard laboratory strain of C. albicans (ATCC SC5317). Disease progression was monitored by daily slit-lamp exam and assigning clinical scores. Following euthanasia, fungal burden was estimated via a serial dilution method. The level of pro-inflammatory cytokines and chemokines was determined by qRT-PCR and ELISA. Neutrophil infiltration was determined by flow cytometry and immunostaining. The extent of retinal tissue damage was assessed by H&E and TUNEL staining. Retinal function was measured by electroretinography (ERG).
Our dose-response study revealed that 6,500 CFU of C. albicans induced reproducible endophthalmitis in both mouse strains. Our time-course experiments revealed that fungal burden is increased by 24 and 48h post-infection, followed by a decline at 72 and 96h. This trend was more pronounced in BALB/c mice than C57BL/6 mice. The levels of pro-inflammatory cytokines followed a similar trend, peaking at 24/48h and declining by 72/96h in both mouse strains. Unexpectedly, PMN infiltration remained high until 120h post-infection. ERG analysis revealed a time-dependent decline in retinal function, which coincided with increased retinal tissue damage, as evidenced by increased retinal detachment/folding and more TUNEL positive cells.
Our results indicate that C. albicans causes endophthalmitis and elicits a significant inflammatory response in the eyes of both C57BL/6 and BALB/c mouse strains. Furthermore, there appears to be no discernible difference in disease outcome between these two models. The establishment of this new mouse model will enable us to evaluate the therapeutic efficacy of antifungal drugs.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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