Cellular mechanisms of blood-retinal barrier dysfunction in macular edema

S. A. Vinores, N. L. Derevjanik, H. Ozaki, N. Okamoto, P. A. Campochiaro

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Purpose: To determine the mechanism of blood-retinal barrier (BRB) dysfunction in human and experimental specimens using immunocytochemistry. Methods: Extravascular albumin was localized in clinical specimens and retinas from transgenic mice that overexpress vascular endothelial growth factor (VEGF) in the photoreceptors. Transgenic mouse retinas were also labeled with Griffonia simplicifolia isolectin-B4 (GSA), a lectin that binds to endothelial cells. Results: The BRB is established by the presence of tight junctions between the retinal vascular endothelial (RVE) cells and the RPE cells and by a paucity of intraendothelial cell vesicles. When BRB breakdown occurs in human ocular disorders such as diabetic retinopathy, retinitis pigmentosa, or cystoid macular edema, staining for extravascular albumin reveals leakage through the tight junctions, an upregulation of intraendothelial vesicles, and permeation of RVE or RPE cells that have undergone degenerative changes. VEGF, in addition to inducing neovascularization (NV), promotes vascular leakage. In VEGF transgenic mice, BRB failure is confined to the outer retina, the area where NV occurs. GSA binds to the luminal and abluminal surfaces of RVE cells in new and established vessels and to intraendothelial vesicles and interendothelial cell junctions in areas of vascular leakage. Conclusion: BRB dysfunction may be mediated by leakage through the tight junctions of RVE or RPE cells, by trans-endothelial vesicular transport, or by permeation of RVE or RPE cells that have undergone degenerative changes. GSA may be a useful marker to assist in recognizing open tight junctions and an increase in intraendothelial cell vesicles, which are indicative of BRB failure.

Original languageEnglish (US)
Pages (from-to)13-24
Number of pages12
JournalDocumenta Ophthalmologica
Issue number3-4
StatePublished - Dec 1 1999


  • Blood-retinal barrier
  • Griffonia simplicifolia isolectin-B4
  • Macular edema
  • Neovascularization
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Physiology (medical)


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