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Atsushi Nonaka, Junichi Kiryu, Akitaka Tsujikawa, Kenji Yamashiro, Kazuaki Miyamoto, Hirokazu Nishiwaki, Yoshihito Honda, Yuichiro Ogura; PKC-β Inhibitor (LY333531) Attenuates Leukocyte Entrapment in Retinal Microcirculation of Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2000;41(9):2702-2706. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. The activity of protein kinase C (PKC), preferentially β isoform of
PKC, has been shown to be elevated in the diabetic retina. Recently,
LY333531, a specific inhibitor of PKC-β, has been reported to improve
the decrease of retinal blood flow in early diabetes. Increased
leukocyte entrapment has been suggested to be involved in blood flow
disturbances in the early diabetic retina. This study was designed
quantitatively to evaluate leukocyte entrapment in the retinal
microcirculation of diabetic rats and the effect of LY333531 on
methods. Diabetes was induced in male Long-Evans rats by intraperitoneal
injection 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 entrapment in the retinal microcirculation was quantitatively
evaluated in vivo with acridine orange digital fluorography.
results. The number of leukocytes trapped in the retinal microcirculation of
diabetic rats (mean ± SEM; 14.3 ± 1.3
cells/mm2) was significantly increased, compared with
nondiabetic control rats (7.5 ± 0.3 cells/mm2; P < 0.0001). Oral administration of LY333531
significantly decreased the number of leukocytes trapped in the retinal
microcirculation of diabetic rats (10.9 ± 0.6, 11.3 ± 0.7,
and 10.4 ± 0.4 cells/mm2 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 entrapment
in the retinal microcirculation during the period of early diabetes.
This effect may contribute to the improvement of abnormal retinal blood
flow in early diabetes with LY333531. LY333531 might have a therapeutic
efficacy in preventing microcirculatory flow disturbances by trapped
leukocytes in the early diabetic retina.
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