The Role of Endothelial Glycocalyx In the Regulation of Retinal Perfusion

Abstract

Introduction The endothelial glycocalyx is a mesh-like network of proteoglycans and glycoproteins present luminally on the endothelium. Both computational and experimental studies suggest that the presence of the glycocalyx regulates microvascular perfusion and promotes homogeneous blood flow. This function of the glycocalyx in the retina has yet to be investigated; therefore, in this study we try to characterize the role of the retinal glycocalyx in the regulation of retinal hemodynamics and perfusion. Methods Hyaluronidase (25 mg/kg body weight) and heparinase I/III (1 U/mouse) were injected i.v. for 30 minutes via femoral vein cannulation to degrade the glycocalyx. Fluorescently labelled red blood cells were used to measure retinal vascular velocity, and fluorescent dextran (MW = 2000 kD) was used to measure diameters and mean circulation times. Blood flow was calculated as velocity ´ p ´ diameter2/4, and arteriolar and venular shear rates were calculated as 8 ´ velocity/diameter. Results In the retina, glycocalyx degradation led to significant increases in both arteriolar (7%, p=0.018) and venular (16%, p=0.003) lumen diameters filled with high molecular weight dextran, with a more prominent effect on venular diameter. Following the loss of glycocalyx, we observed a tendency (not significant) of an increase in arteriolar velocity, however, no effect was observed on venular velocities. The removal of heparan sulfate and hyaluronic acid led to a substantial increase in arteriolar (24%, p=0.02), venular (28%, p=0.0502), and total blood flow (26%, p=0.029). However, no changes were observed in mean circulation time through the retina. Further, the enzymatic treatment led to a significant decrease in venular (14%, p=0.03), but not arteriolar, shear rates. Conclusions Our study suggests that degradation of the glycocalyx can cause changes in retinal perfusion.