title: Blood-Retinal Barrier Compromise and Endogenous Staphylococcus aureus Endophthalmitis.
abstract: OBJECTIVE
  To test the hypothesis that blood-retinal barrier compromise is associated with the development of endogenous Staphylococcus aureus endophthalmitis.
  
  
  METHODS
  To compromise the blood-retinal barrier in vivo, streptozotocin-induced diabetes was induced in C57BL/6J mice for 1, 3, or 5 months. Diabetic and age-matched nondiabetic mice were intravenously injected with 108 colony-forming units (cfu) of S. aureus, a common cause of endogenous endophthalmitis in diabetics. After 4 days post infection, electroretinography, histology, and bacterial counts were performed. Staphylococcus aureus-induced alterations in in vitro retinal pigment epithelial (RPE) cell barrier structure and function were assessed by anti-ZO-1 immunohistochemistry, FITC-dextran conjugate diffusion, and bacterial transmigration assays.
  
  
  RESULTS
  We observed one bilateral infection in a control, nondiabetic animal (mean = 1.54 × 103 ± 1.78 × 10² cfu/eye, 7% incidence). Among the 1-month diabetic mice, we observed culture-confirmed unilateral infections in two animals (mean = 5.54 × 10² ± 7.09 × 10² cfu/eye, 12% incidence). Among the 3-month diabetic mice, infections were observed in 11 animals, three with bilateral infections (mean = 2.67 × 10² ± 2.49 × 10² cfu/eye, 58% incidence). Among the 5-month diabetic mice, we observed infections in five animals (mean = 7.88 × 10² ± 1.08 × 10³ cfu/eye, 33% incidence). In vitro, S. aureus infection reduced ZO-1 immunostaining and disrupted the barrier function of cultured RPE cells, resulting in diffusion of fluorophore-conjugated dextrans and transmigration of live bacteria across a permeabilized RPE barrier.
  
  
  CONCLUSIONS
  Taken together, these results indicated that S. aureus is capable of inducing blood-retinal barrier permeability and causing endogenous bacterial endophthalmitis in normal and diabetic animals.
authors.affiliation: Department of Ophthalmology The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Coburn
authors.affiliation: Oklahoma Center for Neuroscience, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Brandt J
authors.initials: BJ
authors.lastname: Wiskur
authors.affiliation: Department of Ophthalmology The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Astley
authors.affiliation: Department of Ophthalmology The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States 2Oklahoma Center for Neuroscience, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States 3Department.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Callegan
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier; D004195:Disease Models, Animal; D009877:Endophthalmitis / Q000378:metabolism* / Q000382:microbiology; D015818:Eye Infections, Bacterial / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification*