Abstract
Purpose:
To determine the effect of retinal pigment epithelium (RPE) dysfunction on the development of endogenous bacterial endophthalmitis (EBE) and to compare the rates of infection between Klebsiella pneumoniae and Staphylococcus aureus, the leading causes of Gram-negative and Gram-positive EBE, respectively, in mice with dysfunctional RPE.
Methods:
Male C57BL/6J mice were intraperitoneally injected with sodium iodate (NaIO3) (50 mg/kg) to induce RPE permeabilization. Controls consisted of uninjected mice. Control and NaIO3-treated mice were imaged at 24, 72, and 96 hours post-injection using a Micron III Retinal Imaging System. Fluorescein angiography was performed to document retinal vascular permeability using 0.002 mL of AK-FLUOR® 10% (100 mg/mL) injected intraperitoneally two minutes prior to imaging. For infections, control and NaIO3-treated groups were intravenously injected with 10^8 colony forming units (CFU) of the clinical K. pneumoniae strain KLP02, or S. aureus strain 8325-4, 24 hours following NaIO3 treatment. At 96 hours post-infection, eyes were analyzed by slit lamp biomicroscopy and harvested for bacterial counts.
Results:
Maximum permeability of the RPE was observed at 24 hours post-NaIO3 injection. At 96 hours post-infection, 3 of 10 NaIO3-treated mice and 0 of 10 control mice infected with K. pneumoniae developed EBE. The mean CFU per eye among the NaIO3-treated mice was 3.04x10^2 (±3.42x10^2). Six of 10 RPE permeabilized mice and 2 of 10 control mice infected with S. aureus developed EBE. The mean CFU per eye for the NaIO3-treated mice was 2.72×10^2 (±3.12x10^2) and for the control mice was 2.48×10^2 (±2.77x10^2). RPE permeabilization resulted in a 30% K. pneumoniae and 60% S. aureus EBE incidence.
Conclusions:
The results demonstrate a correlation between NaIO3-induced RPE dysfunction and an increase in EBE incidence, supporting the hypothesis that the permeability of the RPE is a potential mechanism by which EBE develops. Further, the incidence of S. aureus EBE was higher than the incidence of K. pneumoniae EBE in NaIO3-treated mice, suggesting that S. aureus is more virulent in this model than K. pneumoniae. The fact that EBE developed in control mice infected with S. aureus suggests a different mechanism for EBE with this organism. Future studies will continue to explore the relationship between changes in vascular permeability in underlying diseases and the development of EBE.
Keywords: 513 endophthalmitis •
594 microbial pathogenesis: experimental studies •
701 retinal pigment epithelium