Blocking ET-1 receptors does not correct subnormal retinal oxygenation response in experimental diabetic retinopathy.
Blocking ET-1 receptors does not correct subnormal retinal oxygenation response in experimental diabetic retinopathy.
复制标题
阻断 ET-1 受体并不能纠正实验性糖尿病视网膜病变中低于正常的视网膜氧合反应。
DOI：
10.1167/iovs.05-1624
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Berkowitz,BruceA
中科院分区：
文献类型：
--
作者：
Roberts,Robin;Luan,Hongmei;Berkowitz,BruceA
purpose. To test the hypothesis that bosentan (a dual ET A/ET B receptor antagonist) corrects a subnormal retinal oxygenation response in the STZ-induced diabetic rat.methods. In benchtop experiments, ET-1 was acutely injected into the vitreous of control and 5-to 7-day bosentan-treated nondiabetic rats. Major retinal vessel diameters were analyzed from ADPase-stained flatmounts. Retinal oxygenation (ΔP o 2), an established early surrogate marker of drug treatment efficacy, was measured by MRI during a 2-minute carbogen inhalation challenge in four groups: control rats (n= 7), control rats treated with bosentan (n= 7), 3-month diabetic rats (n= 9), and 3-month diabetic rats treated with bosentan (n= 5). Effect of baseline differences was studied in control rats breathing either room air (n= 5) or 12% oxygen breathing (n= 5) before a 2-minute carbogen provocation.results. ET-1 produced a significant (P< 0.05) reduction in retinal arterial diameter that was suppressed (P> 0.05) in rats fed bosentan chow admix. For all groups, no MRI baseline signal intensity differences were found (P> 0.05). Also, comparisons between baseline room air and 12% conditions and control rats fed normal chow or a bosentan admix both produced similar (P> 0.05) panretinal ΔP o 2. In treated and untreated diabetes groups, inferior hemiretinal ΔP o 2 remained normal (P> 0.05), but superior hemiretinal ΔP o 2 was subnormal (P< 0.05).conclusions. Because subnormal retinal ΔP o 2 after drug treatment is a biomarker of subsequent vascular histopathology, the present data raise the possibility that retinal ET-1 does not play a key role in the pathogenesis of diabetic retinopathy.
