Measurement of blood-retinal barrier breakdown in endotoxin-induced endophthalmitis.
Endophthalmitis is a severe inflammatory disorder with profound visual consequences. Treatment of this disorder has been limited by the lack of quantitative information regarding retinal responses to severe inflammation. The purpose of this study was to measure the effect of endotoxin-induced endophthalmitis on blood-retinal barrier (BRB) function in vivo using contrast-enhanced magnetic resonance imaging (MRI). Endophthalmitis was produced by injecting Escherichia coli endotoxin into the midvitreous of pigmented rabbits. Contrast-enhanced MRI was performed at selected intervals thereafter. In all cases, a clinical grading system was used to assess the severity of inflammation before imaging. In a dose-response experiment, total vitreous protein was measured from vitreous specimens obtained 1 day after endotoxin injection and immediately after the imaging procedure. At 1 day after injection, endotoxin produced a selective breakdown of the inner BRB at all doses evaluated (0.01 microgram to 500 micrograms). Permeability-surface area product normalized to the area of leaky retina (PS') increased from 1.35 +/- 0.78 x 10(-4) cm/minute (mean +/- SEM, n = 4 eyes) at a dose of 0.01 microgram to 8.15 +/- 2.22 x 10(-4) cm/minute n = 4) eyes) at a dose of 10 micrograms. Inner BRB integrity was restored by day 28 after injection. In general, changes in PS', blood-aqueous barrier leakage, mean clinical score, and vitreous protein concentration were found, but the correlation between any two of these parameters was poor. Leakage of contrast appears early in the course of endotoxin-induced endophthalmitis and is a self-limited process. In future studies, these quantifiable changes in BRB permeability should prove useful in the assessment of various therapeutic interventions.