Retinal blood flow abnormalities following six months of hyperglycemia in the Ins2(Akita) mouse

Abstract

The aim of this study was to characterize the microvascular flow abnormalities and oxygenation changes that are present following six months of hyperglycemia in the diabetic Ins2(Akita) mouse. Previous studies have shown decreased retinal blood flow in the first several weeks of hyperglycemia in rodents, similar to the decreases seen in the early stages of human diabetes. However, whether this alteration in the mouse retina continues beyond the initial weeks of diabetes has yet to be determined, as are the potential consequences of the decreased flow on retinal oxygenation. In this study, male Ins2(Akita) and age-matched C57BL/6 (non-diabetic) mice were maintained for a period of six months, at which time intravital microscopy was used to measure retinal blood vessel diameters, blood cell velocity, vascular wall shear rates, blood flow rates, and transient capillary occlusions. In addition, the presence of hypoxia was assessed using the oxygen-sensitive probe pimonidazole. The diabetic retinal microvasculature displayed decreases in red blood cell velocity (30%, p<0.001), shear rate (25%, p<0.01), and flow rate (40%, p<0.001). Moreover, transient capillary stoppages in flow were observed in the diabetic mice, but rarely in the non-diabetic mice. However, no alterations were observed in retinal hypoxia as determined by a pimonidazole assay, suggesting the possibility that the decreases seen in retinal blood flow may be dictated by a decrease in retinal oxygen utilization.