Leukostasis and Microcirculation in Retina of Insulin Resistance Models

Abstract

Abstract: : Purpose: Leukocyte adhesion to the retinal vasculature is increased in diabetic rats and may lead to retinal endothelial cell injury. Hyperglycemia-induced activation of ICAM-1 in retinal vascular endothelial cells was reported to increase retinal leukostasis, but it is unclear if the increase in leukostasis could induce diabetic retinopathy. Zucker fatty rats are models of insulin resistance which do not have hyperglycemia or retinopathy but are reported to have endothelial dysfunction in large vessels. In the current study, we examined whether there is increased retinal leukostasis and reduced retinal microcirculation in the Zucker Fatty rat model as compared to short duration diabetic rats. Methods: Retinal leukostasis was observed by infusing acridine orange (4 mg/kg at 1.5 ml/min) through a jugular catheter. Retinal fundus images were obtained with a scanning laser ophthalmoscope (SLO). Stationary leukocytes in the capillary bed were counted 20 minutes after the injection of acridine orange. Retinal leukostasis was evaluated by dividing the number of stationary leukocytes by the retinal area represented by 10 40° fields centered on the optic disc. Retinal microcirculation was evaluated by measuring retinal mean circulation time (MCT) using video fluorescein angiography(VFA). Results: The blood glucose levels for fatty rats (110 ± 9 mg/dl: mean ± SD) were slightly higher than for lean rats (96 ± 11 mg/dl, p<0.01). Leukostasis of fatty rats was increased by 98±62% (12.14 ± 4.26 cells/pixel2 x 10-5 , n=10) as compared to lean rats (6.18 ± 2.35 cells/pixel2 x 10-5, n=9, p<0.01). There was no significant difference in MCT between fatty rats (1.03 ± 0.11 sec, n=10) and lean rats (0.98 ± 0.08 sec, n=9). Conclusions: Since insulin-resistant Zucker fatty rats demonstrate increased retinal leukostasis but do not have altered retinal circulation time, these results suggest that endothelial injuries may appear in retinal capillaries through increased leukostasis; however, leukostasis does not cause the reduction reduction in retinal microcirculation observed early in diabetic retinopathy.

Keywords: diabetic retinopathy • animal model • pathobiology