Diabetic retinopathy, a cause of
blindness, is often associated with the upregulation of
vascular endothelial growth factor (
VEGF) in the retina. Recently, leukocyte adhesion (
leukostasis) is claimed for the occlusion of
retinal capillary vascularity, which ultimately assists in the progression of
diabetic retinopathy. In addition,
intercellular adhesion molecule-1 (ICAM-1), a representative factor for
leukostasis, is increased in diabetic retina.
Endothelin (ET)-1, a potent
vasoconstrictor peptide, is closely linked to the pathogenesis of
diabetic retinopathy. Different therapeutic interventions concerning
VEGF have already been proposed to prevent
diabetic retinopathy. However, no study has yet reported concerning the effects of ET-1 receptor antagonist on the upregulated
VEGF and
ICAM-1 in morphologically intact diabetic retina. The current study investigated the effect of ET(A) receptor antagonist (
TA-0201; 1 mg kg(-1) day(-1)) on the expressions of
VEGF and
ICAM-1 in rat diabetic retina. Diabetes was induced by
intraperitoneal injection of
streptozotocin (70 mg/kg) in Sprague-Dawley rats, whereas control rats (Cont) received only
citrate buffer. After 1 week, the
streptozotocin-administered rats were randomly divided into two groups: ET(A) receptor antagonist-treated group (DM+TA-0201) and saline-treated group (DM+vehicle). After the treatment for 4 weeks, the retina was removed from the eyeball. In DM+vehicle group, the
VEGF expression of retina was significantly increased (33.5 pg/mg) in comparison with that in the Cont group (25.1 pg/mg), and the upregulation of
VEGF was reversed in DM+TA-0201 group (26.9 pg/mg), a phenomenon consistent with the change in
VEGF mRNA levels. The expression of
retinal ICAM-1 was increased in DM+vehicle group (55.1 pg/mg) compared with Cont group (43.8 pg/mg), and ET antagonism completely blocked this increase (43.8 pg/mg). Moreover, an increased
leukostasis by 3.3-fold in DM+vehicle retina was returned to the control level by ET antagonism. In the current study, there was no obvious
retinal morphological alteration from both the
hematoxylin and
eosin staining and the
FITC-dextran angiography. Thus, ET(A) receptor antagonist might be useful in preventing the progression of
diabetic retinopathy, as evidenced by suppressing the increase in
VEGF and
ICAM-1 levels as well as
leukostasis in morphologically intact diabetic retina.