The Endothelial Glycocalyx and Retinal Hemodynamics

Abstract

Purpose. Previous studies suggest that the endothelial glycocalyx adds to vascular resistance, inhibits thrombosis, and is critical for regulating homogeneous blood flow and ensuring uniform red blood cell (RBC) distribution. However, these functions and consequences of the glycocalyx have not been examined in the retina. We hypothesize that the endothelial glycocalyx is a critical regulator of retinal hemodynamics and perfusion and decreases the propensity for retinal thrombus formation. Methods. Hyaluronidase and heparinase, which are endothelial glycocalyx-degrading enzymes, were infused into mice. Fluorescein isothiocyanate–dextran (2000 kDa) was injected to measure lumen diameter, while RBC velocity and distribution were measured using fluorescently labeled RBCs. The diameters and velocities were used to calculate retinal blood flow and shear rates. Mean circulation time was calculated by measuring the difference between arteriolar and venular mean transit times. Rose Bengal dye was infused, followed by illumination with a green light to induce thrombosis. Results. The acute infusion of hyaluronidase and heparinase led to significant increases in both arteriolar (7%) and venular (16%) diameters in the retina, with a tendency towards increased arteriolar velocity. In addition, the degradation caused a significant decrease in the venular shear rate (14%). The enzyme infusion resulted in substantial increases in total retinal blood flow (26%) and retinal microhematocrit but no changes in the mean circulation time through the retina. We also observed an enhanced propensity for retinal thrombus formation with the removal of the glycocalyx. Conclusions. Our data suggest that acute degradation of the glycocalyx can cause significant changes in retinal hemodynamics, with increases in vessel diameter, blood flow, microhematocrit, pro-thrombotic conditions, and decreases in venular shear rate.