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Neha Gupta, Pawan Kumar Singh, Sanjay G Revankar, Pranatharthai H Chandrasekar, Ashok Kumar; Pathogenesis of Aspergillus Endophthalmitis in Immunocompetent and Neutropenic Mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2544. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Aspergillus (A.) fumigatus is a leading cause of both exogenous endophthalmitis following traumatic injury to the eye and endogenous endophthalmitis in immunocompromised individuals. However, the pathogenesis of Aspergillus endophthalmitis is not well understood. The aim of this study is to develop a mouse model of A. fumigatus endophthalmitis and investigate its pathophysiology in immunocompetent versus immunocompromised (neutropenic) mice.
Endophthalmitis was induced in C57BL/6 mice by intravitreal injections of ~10,000 CFU of A. fumigatus. Immunocompromised mice received intraperitoneal injections of anti-Ly6G-1A8 to deplete their neutrophils 24 hours prior to A. fumigatus challenge. Disease progression was monitored by assessing corneal haze and opacity, fundus imaging, and fungal burden estimation. qRT PCR and ELISA were used to measure the levels of inflammatory cytokines/chemokines. Flow cytometry and immunostaining were used to assess PMN infiltration. Histological analysis was used to assess retinal tissue damage.
C57BL/6 mice challenged by intravitreal inoculation of A. fumigatus resulted in the induction of endophthalmitis as evidenced by increased corneal haze and opacity two days post infection (dpi). Aspergillus infected eyes exhibited increased PMN infiltration, production of inflammatory mediators, heavy cellular infiltrates, and the disruption of normal retinal architecture. Infected neuroretina also exhibited significant upregulation of pathogen recognizing receptors such as Toll-like receptors. Depletion of neutrophils results in greater fungal burden, increased levels of IL6 and significantly reduced levels of IL1β, in comparison to immunocompetent (PMN+/+) mice.
Our findings indicate an essential role of neutrophils in providing innate retinal defense against Aspergillus endophthalmitis. Moreover, this immunocompetent murine model of fungal aspergillus endophthalmitis can be utilized to study the pathogenesis of exogenous fungal endophthalmitis and evaluate the therapeutic efficacy of existing and new ocular antifungal agents.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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