@article{10.1167/iovs.05-1624,
    author = {Roberts, Robin and Luan, Hongmei and Berkowitz, Bruce A.},
    title = "{Blocking ET-1 Receptors Does Not Correct Subnormal Retinal Oxygenation Response in Experimental Diabetic Retinopathy}",
    journal = {Investigative Ophthalmology & Visual Science},
    volume = {47},
    number = {8},
    pages = {3550-3555},
    year = {2006},
    month = {08},
    abstract = "{  purpose. To test the hypothesis that bosentan (a dual ETA/ETB 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 (ΔPo 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 ΔPo 2. In treated and untreated diabetes groups, inferior hemiretinal ΔPo 2 remained normal (P \\> 0.05), but superior hemiretinal ΔPo 2 was subnormal (P \\< 0.05).  conclusions. Because subnormal retinal ΔPo 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. }",
    issn = {1552-5783},
    doi = {10.1167/iovs.05-1624},
    url = {https://doi.org/10.1167/iovs.05-1624},
    eprint = {https://arvojournals.org/arvo/content\_public/journal/iovs/932940/z7g00806003550.pdf},
}