title: Bacillus cereus-induced permeability of the blood-ocular barrier during experimental endophthalmitis.
abstract: OBJECTIVE
  The purpose of this study was to determine to what extent blood-retinal 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 colony-forming units of B. cereus, and eyes were analyzed at specific times after infection 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 retinal pigment epithelium.
  
  
  RESULTS
  B. cereus induced the leakage of albumin and fibrin into the aqueous and vitreous humor by 8 hours after infection. BRB permeability occurred as early as 4 hours and increased 13.30-fold compared with uninfected controls by 8 hours. Production of proinflammatory cytokines IL-6, MIP-1alpha, IL-1beta, and KC increased over the course of infection. In the retina, ZO-1 disruption began by 4 hours and was followed by decreasing occludin and ZO-1 expression at 4 and 8 hours, respectively. Tubulin condensation and RPE65 degradation occurred by 12 hours. A quorum-sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. 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 hours after infection. Disruption of tight junctions at the level of the retinal pigment epithelium may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Moyer
authors.forename: Raniyah T
authors.initials: RT
authors.lastname: Ramadan
authors.forename: Billy D
authors.initials: BD
authors.lastname: Novosad
authors.forename: Roger
authors.initials: R
authors.lastname: Astley
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Callegan
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001409:Bacillus cereus / Q000502:physiology*; D001813:Blood-Retinal Barrier / Q000382:microbiology*; D015153:Blotting, Western; D002199:Capillary Permeability / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D009877:Endophthalmitis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005337:Fibrin / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; D012709:Serum Albumin; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D005337:Fibrin