PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats

PURPOSE. The activity of protein kinase C (PKC), preferentially beta isofor m of PKC, has been shown to be elevated in the diabetic retina. Recently, L Y333531, a specific inhibitor of PKC-beta, has been reported to improve the decrease of retinal blood flow in early diabetes. Increased leukocyte entr apment has been suggested to be involved in blood flow disturbances in the early diabetic retina. This study was designed quantitatively to evaluate l eukocyte entrapment in the retinal microcirculation of diabetic rats and th e effect of LY333531 on leukocyte entrapment. METHODS. Diabetes was induced in male Long-Evans rats by intraperitoneal in jection of streptozotocin (60 mg/kg). LY333531 (0.1, 1.0, or 10.0 mg/kg/d) was administered orally during a 4-week diabetic period. Leukocyte entrapme nt in the retinal microcirculation was quantitatively evaluated in vivo wit h acridine orange digital fluorography. RESULTS. The number of leukocytes trapped in the retinal microcirculation o f diabetic rats (mean +/- SEM; 14.3 +/- 1.3 cells/mm(2)) was significantly increased, compared with nondiabetic control rats (7.5 +/- 0.3 cells/mm(2); P < 0.0001). Oral administration of LY333531 significantly decreased the n umber of leukocytes trapped in the retinal microcirculation of diabetic rat s (10.9 +/- 0.6, 11.3 +/- 0.7, and 10.4 +/- 0.4 cells/mm(2) with LY333531 0 .1, 1.0, and 10.0 mg/kg/d, respectively; P < 0.05). CONCLUSIONS. Treatment with LY333531 attenuated the increase of leukocyte e ntrap,ment in the retinal microcirculation during the period of early diabe tes. This effect may contribute to the improvement of abnormal retinal bloo d flow in early diabetes with LY333531. LYS333531 might have a therapeutic efficacy in preventing microcirculatory flow disturbances by trapped leukoc ytes in the early diabetic retina.