Mitigation of neutrophil infiltration in a rat model of early Staphylococcus aureus endophthalmitis.

Abstract

Infectious endophthalmitis is characterized by neutrophil migration into the eye. The purpose of this study was to determine whether systemic neutrophil depletion mitigates the ocular influx of neutrophils during the early phases of experimental endophthalmitis. Endophthalmitis was induced in rats by intravitreal injection of Staphylococcus aureus. Animals received a single systemic dose of an anti-neutrophil-depleting antibody (dAb) or normal rabbit serum (NRS) 6 or 12 hours after intravitreal injection. Inflammation was graded both in vivo and by histopathology. Myeloperoxidase (MPO) was used as a biomarker of neutrophil infiltration. Bacterial clearance was evaluated by determining the amount of viable bacteria recovered from ocular specimens. Rats that received dAb 6 hours after bacterial injection exhibited significantly lower clinical scores, MPO activity, fewer vitreous exudates, and higher vitreous bacterial counts at 24 hours (P < 0.05). As the neutrophil population returned in this group, measured by the number in the peripheral blood, increasing intraocular inflammation was observed. Rats receiving dAb 12 hours after vitreous injection also demonstrated significantly lower clinical scores, MPO activity and less vitreous exudates at the 24-hour time point (P < 0.05). No significant differences from the control were detected at any of the subsequent time points, except in bacterial counts and MPO activity. Depletion of neutrophils early in the inflammatory response delayed the onset of severe ocular inflammation but also prevented adequate bacterial clearance. These results confirm the important role of neutrophils in ocular host defense during the early stages of experimental endophthalmitis.