Mechanism of blood-retinal barrier breakdown by soluble mediators revealed by electron microscopic immunocytochemistry

J. D. Luna, S. A. Vinores, N. Derevjanik, P. A. Campochiaro

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. Soluble mediators have been implicated in blood-retinal barrier (BRB) breakdown leading to macular edema, a major cause of visual loss in inflammatory eye disease, diabetic retinopathy and other retino vascular occlusive disease and after intraocular surgery. This study was performed to evaluate the effects on the BRB of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF- α) and interleukin-1 beta (IL-1 β), which have been implicated in some of these processes. Methods. Pigmented rabbits received intravireal injections of VEGF (50ng/100μl), TNF-α (50ng/100μl) or IL-1-β (500 U/100μl). As a control, contra-lateral eyes were injected with 100μl of saline. The eyes were fixed at 6 or 24 hours after injection, immunocytochemically stained for albumin, and examined by electron microscopy. Results. All of the mediators investigated caused the inter - endothelial tight junctions of the retinal vessels to open morphologically and functionally. Ultrastructural examination showed that a high percentage of retinal vascular endothelial (RVE) tight junctions of rabbits treated with VEGF (33%), TNF-α (32%), on IL-1β (17%) appeared open along their entire length compared with saline-injected controls (8%). Many of the junctions also appeared to be functionally open, based on the demonstration of albumin extending from the luminal surface to the perivascular basement membrane. In addition, each mediator generated an increase in albumin-filled, vesicle-like structures in the RVE cytoplasm. Conclusion. VEGF, TNF-α and IL-1β all appear to cause BRB breakdown by opening tight junctions between RVE cells and by increasing vesicular transport through RVE cells.

Original languageEnglish (US)
Pages (from-to)S967
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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