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Abstract
PURPOSE: Leukocytes have been reported to be less deformable and more activated in diabetes. It has also been suggested that they cause microvascular occlusions that may cause diabetic microangiopathy. This study was designed to evaluate in vivo leukocyte dynamics in the retinal microcirculation of diabetic rats. METHODS: Streptozotocin (STZ)-induced diabetic rats 4 weeks after diabetes induction and spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats with 6 weeks' duration of diabetes were used in this study. Leukocyte dynamics were observed with acridine orange digital fluorography, using a nuclear fluorescent dye of acridine orange and high-resolution images from a scanning laser ophthalmoscope. RESULTS: There was no significant difference in capillary leukocyte velocity between the STZ-induced diabetic rats (1.27 +/- 0.12 mm/sec, mean +/- SD) and nondiabetic control subjects (1.38 +/- 0.07 mm/sec) or between OLETF rats (1.31 +/- 0.17 mm/sec) and the nondiabetic controls, Long-Evans Tokushima Otsuka (LETO) rats (1.29 +/- 0.11 mm/sec). In contrast, the density of leukocytes trapped in the retinal microcirculation was significantly elevated in the STZ-induced diabetic (2.5-fold; P < 0.01) and the OLETF rats (2-fold; P < 0.01) compared with leukocyte density in the control subjects. CONCLUSIONS: Pharmacologically induced and spontaneously diabetic rats showed increased leukocyte entrapment in the living retina in the early stages of diabetes. In light of the damaging potential of leukocytes, accumulation of leukocytes in diabetic retinas from the preretinopathy stage could cause microvascular occlusions and dysfunction, in turn causing diabetic retinopathy.