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Bruce A. Berkowitz, Robin Roberts, Hongmei Luan, Jamie Peysakhov, Deborah L. Knoerzer, Jane R. Connor, Thomas C. Hohman; Drug Intervention Can Correct Subnormal Retinal Oxygenation Response in Experimental Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2005;46(8):2954-2960. https://doi.org/10.1167/iovs.05-0132.
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purpose. Early subnormal retinal oxygenation response to a hyperoxic provocation (ΔPo 2) is strongly associated with subsequent experimental diabetic retinopathy and can be reversed by drug treatments started with the induction of diabetes. It is not yet known whether drug treatment can reverse an established subnormal ΔPo 2.
methods. Retinal ΔPo 2 was measured in two separate experimental paradigms in streptozotocin-induced diabetic rats. In a prevention study, measurements were performed in untreated diabetic rats, 3 months after the initiation of hyperglycemia (D3mo), in age-matched nondiabetic rats (C3mo), and in diabetic rats treated orally for 3 months with celecoxib, a cyclooxygenase (COX)-2-selective inhibitor, (D3mo+COX2i). In an intervention study, measurements were performed in untreated diabetic rats 4 months after the initiation of diabetes (D4mo), in age-matched nondiabetic rats (C4mo), and in diabetic rats that were untreated for 3 months and then were orally treated for an additional month with either celecoxib (D4mo+COX2i) or l-N (6)-(1-iminoethyl)lysine 5-tetrazole amide, a prodrug of an inhibitor of inducible nitric oxide synthase (iNOS, D4mo+ iNOSi).
results. In the prevention arm, subnormal (P < 0.05) retinal ΔPo 2 was found in the D3mo group, but not in the D3mo+COX2i group (P > 0.05). In a previous study, it was reported that retinal ΔPo 2 also corrected in a D3mo+iNOSi group. In the intervention arm, retinal ΔPo 2 levels in the D4mo and D4mo+iNOSi, but not the D4mo+COX2i, groups were (P < 0.05) subnormal.
conclusions. These results demonstrate, for the first time, that drug treatment can reverse an established subnormal ΔPo 2. Furthermore, this effect could not be predicted by a drugs’ ability to prevent the development of subnormal ΔPo 2.
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