Abstract
Purpose :
The blood-retinal-barrier may be a surrogate for assessing blood-brain-barrier integrity. If so, systemic disruption of tight junctions should produce similar effects on fluorescein angiography dynamics in both tissues. We compare the angiography dynamics in rat retina and brain before and after blood-neural-barrier (BNB) disruption.
Methods :
Sodium fluorescein (1%, 70μl, 1.05ml/min) was injected via the femoral vein in anesthetized (60:5mg/kg ketamine:xylazine) adult Long-Evans rats and angiography recorded (Micron III) at 30 frames/sec for 1 min. An area of skull was thinned to image vasculature on the cortical surface. Angiography of naïve eyes (n=26) and brains (n=18) established baseline profiles.
Angiography was performed at 6 and 24 hours after BNB disruption with IV sodium deoxycholate (1ml 0.06M DOC, 33μl/min, n=10/group). Controls received saline (1ml). Each pixel’s time-luminance profiles were analysed (MATLAB) to return time to 50% maximum (filling), 50% decay (drainage) and fluorescence at 1 min (residual, %). Frequency histograms described the distribution of indices before and after BNB disruption. Level of injury was quantified by the percentage of pixels showing indices beyond the upper quartile (>75%) of control.
Results :
Angiography luminance profiles have similar shapes in both tissues, with a rapid increase in fluorescence and exponential-like decay. Cortical arteries filled faster (all p<0.05) than retinal arteries (mean±SEM, brain 5.6±0.2s, eye 6.6±0.1s) and also decayed faster (brain 10.3±0.2s, eye 11.0±0.1s). The residual was significantly brighter in the brain (brain artery 34.7±2.7%, eye 12.3±0.3%). Similar differences were observed in capillaries and veins (p<0.05).
Following DOC injection fluorescein filling and decay was similar at 6 and 24 hours in both tissues. The residual in capillaries, an indicator of vascular leakage, was elevated compared to control at 6 hours in the eye (brain -0.1±8.9%, eye +22.3±10.6%) but at 24 hours in the brain (brain +40.5±10.1%, eye -18.2±2.9%).
Conclusions :
Spatial and temporal analysis of fluorescein angiography in the eye and brain showed subtle differences in filling and decay. Cortical vessels were brighter due to lack of pigment in the brain. Disruption of tight junctions with DOC affected the BNB of the eye earlier than the brain (6 vs 24 hours) possibly due to differences in blood flow and BNBs in the two tissues.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.