Bacillus cereus Induces Permeability of the Blood Ocular Barrier During Experimental Endophthalmitis
Andrea L Moyer 1,
Raniyah T Ramadan 2,
Billy D Novosad 3,
Roger Astley 4,
and
Michelle C. Callegan 5*
1 Microbiology and Immunology, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States
2 Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States
3 Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
4 Ophthalmology, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States
5 Ophthalmology, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States; Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States; Microbiology and Immunology, University of Oklahoma Health Science Center, Dean A. McGee Eye Institute, Oklahoma City, Oklahoma, United States
* To whom correspondence should be addressed. E-mail: michelle-callegan{at}ouhsc.edu.
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Abstract |
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Purpose. The purpose of this study was to determine to what extent blood retina barrier (BRB) permeability occurred during experimental Bacillus cereus endophthalmitis and whether tight junction alterations were involved in permeability.
Methods. Mice were intravitreally injected with 100 CFU B. cereus and eyes were analyzed at specific times postinfection for permeability to fibrin and albumin, quantitation of intraocular plasma constituent leakage, production of inflammatory cytokines, and alterations in tight junction protein localization and expression at the level of the RPE.
Results. B. cereus-induced leakage of albumin and fibrin into the aqueous and vitreous humor by 8 h postinfection. BRB permeability occurred as early as 4 h and increased 13.30-fold compared to uninfected controls by 8 h. Production of proinflammatory cytokines IL-6, MIP-1
, IL-1
, and KC increased over the course of infection. In the retina, ZO-1 disruption begins by 4 h, followed by decreasing occludin and ZO-1 expression at 4 and 8 h, respectively. Tubulin condensation and RPE65 degradation occurred by 12 h. A quorum sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. Both wild-type and mutant B. cereus sterile supernatants induced blood ocular barrier permeability similarly to that of wild-type infection.
Conclusions. These results indicate that BRB permeability occurs during the early stages of experimental B. cereus endophthalmitis, beginning as early as 4 h postinfection. Disruption of tight junctions at the level of the RPE may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability.
Key Words:
endophthalmitis, Bacillus cereus, toxins, RPE, tight junctions
