Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction

PLoS One. 2016 May 19;11(5):e0154560. doi: 10.1371/journal.pone.0154560. eCollection 2016.


The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is not required for the development of EBE, but toxin production may facilitate EBE pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiography
  • Animals
  • Blood-Retinal Barrier / microbiology*
  • Cell Survival
  • Cells, Cultured
  • Coloring Agents / chemistry
  • Dextrans
  • Diabetic Retinopathy / pathology
  • Endophthalmitis / microbiology
  • Evans Blue / chemistry
  • Eye Infections, Bacterial / microbiology*
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Humans
  • Immunohistochemistry
  • Iodates / chemistry
  • Klebsiella pneumoniae
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / microbiology*
  • Retinal Vessels / pathology
  • Staphylococcus aureus


  • Coloring Agents
  • Dextrans
  • Iodates
  • fluorescein isothiocyanate dextran
  • Evans Blue
  • Fluorescein-5-isothiocyanate
  • sodium iodate

Associated data

  • figshare/10.6084/m9.figshare.3187533