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M. Engelbert, M.S. Gilmore; Role of complement in host defense against S.aureus endophthalmitis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1004.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the role of the complement system in the host defense against intraocular infection with S.aureus by comparing knockout mice deficient in the central complement cascade component C3 with their WT counterparts. Methods: C3–/– and C57/BL6 (WT) mice were infected intravitreally with 500 and 5,000 CFU S.aureus and the course of infection was followed by determining (1) intraocular bacterial numbers, (2) retinal function, and (3) morphological damage and inflammation by histopathology and FACS analysis. Results:(1) In WT eyes injected with 500 CFU, S.aureus grew up to a maximum 1x107CFU/ml by 24 hours, but was eliminated by 96 hours. In the WT eyes injected with 5,000 CFU, S. aureus grew up to 3x108 CFU/ml by 24 hours and increased to 2x109CFU/ml by 72h. C3–/– eyes injected with 500 CFU reached transiently significantly higher levels than their WT counterparts, but eventually followed a similar course. (2) In WT and C3–/– eyes injected with 500 CFU, retinal function only decreased transiently and recovered to 66% by 72 hours. In WT eyes injected with 5,000 CFU, retinal function was completely lost by 24 hours. (3) By 24 hours WT and C3–/– eyes injected with 500 CFU were infiltrated with similar numbers of inflammatory cells, consisting virtually exclusively of granulocytes. Numbers decreased thereafter without overt retinal pathology. In eyes injected with 5,000 CFU inflammatory cells completely filled the intraocular space by 48 hors. Retinal and uveal tissue were destroyed by that time. Conclusions: The tipping point for a good versus a bad outcome in this murine model of endophthalmitis lies between 500 and 5,000 CFU S.aureus. This point is identical in animals deficient in complement activation. Complement contributes nominally to reducing bacterial numbers early in infection but is not required for eventual clearance of infection and preservation of retinal morphology and function.
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