Fas Ligand but Not Complement is Critical for Control of Experimental Staphylococcus Aureus Endophthalmitis

Purpose: To determine the role of complement and Fas Ligand (FasL) in the host defense against Staphylococcus aureus endophthalmitis.

Methods: C3-/-, FasL defective gld, and C57/BL6 (wild-type [WT]) mice were infected intravitreally with 500 and 5000 CFU S. aureus, and the course of infection was followed by determining the intraocular bacteria counts, retinal function by ERG, and morphologic damage and inflammation by histopathology and flow cytometry.

Results: In WT eyes injected with 500 CFU, S. aureus grew to 1 x 10(7) CFU/mL by 24 hours, but was cleared by 96 hours. In the WT eyes injected with 5000 CFU, S. aureus grew to 2 x 10(9) CFU/mL by 72 hours, resulting in corneal perforation. C3-/- eyes injected with 500 CFU reached transiently higher levels than their WT counterparts (P < 0.001), but eventually followed a similar course. Bacterial counts in gld eyes infected with 500 CFU were similar to those in WT eyes infected with 5000 CFU. In WT and C3-/- eyes injected with 500 CFU, retinal function decreased only transiently and recovered to 66% in 72 hours. In WT eyes injected with 5000 CFU and gld eyes infected with 500 CFU, retinal function was completely lost by 24 hours. By 24 hours, WT and C3-/- eyes injected with 500 CFU were infiltrated with a similar number of granulocytes, but recruitment was significantly impaired in gld eyes (P < 0.005). Cell counts in WT and C3-/- eyes decreased thereafter without overt retinal disease. In eyes injected with 5000 CFU and gld eyes infected with 500 CFU, inflammatory cells completely filled the intraocular space by 48 hours. Retinal and uveal tissue was 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 5000 CFU S. aureus. This point is identical in animals deficient in complement activation, suggesting that complement does not play a significant role in the ocular defense against intraocular bacteria. In contrast, FasL was found to be critical for clearance, since animals deficient in FasL signaling were unable to control infection with 500 CFU.