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Micah James Guthrie, Jennifer J Kang Mieler; Direct measurement of intraretinal nitric oxide in early diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1039.
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© ARVO (1962-2015); The Authors (2016-present)
It is known that nitric oxide (NO) levels are altered in diabetic retinopathy (DR). Recently, we have developed a NO sensor that can measure the intraretinal NO concentration. The purpose of this study is to measure intraretinal NO levels in an early stage of DR.
Long-Evans rats received an intraperitoneal injection of streptozotocin and NO measurements were made three weeks after the injection. Diabetic rats were grouped into moderate blood glucose (MBG, 250-400 mg/dL) or high blood glucose (HBG, >500 mg/dL) groups. Retinal NO measurements were made using a custom-made double-barreled microelectrode that measured NO and recorded the electroretinogram (ERG). The intraretinal ERGs were used to determine retinal depth, allowing for construction of a retinal NO profile. Diabetic NO measurements were compared to control NO measurements from healthy rats and healthy rats that received an intravitreal injection of nitric oxide synthase (NOS) inhibitor L-NG-nitroarginine methyl ester (L-NAME). HBG diabetics also received intravenous injections of L-arginine (50-500 mg/kg BW) after control profiles were recorded.
NO concentration at the choroid/retina boundary was 2.32 ± 0.27 µM for controls. MBG diabetics had significantly higher NO concentration at 3.73 ± 0.39 µM (p=0.007). HBG diabetics and L-NAME profiles had significantly lower NO concentration at 0.924 ± 0.12 µM (p=0.005) and 0.83 ± 0.15 µM for L-NAME (p=0.014), respectively. NO concentration at the retina/vitreous boundary was 1.18 ± 0.11 µM for controls. MBG diabetics were not significantly different from control at 1.54 ± 0.19 µM (p=0.28). HBG and L-NAME profiles were significantly lower than control at 0.39 ± 0.08 µM (p=0.002) and 0.28 ± 0.06 µM (p=0.006), respectively. L-arginine injection did not alter NO levels of HBG diabetics (p=0.32).
To date, this study is the first to measure intraretinal NO levels in control and diabetic rats. High levels of NO in MBG diabetics and low levels in HBG diabetics are unexpected and suggest a non-linear relationship of NO and blood glucose level. The similarity of HBG diabetic and L-NAME profiles and the unresponsiveness of NO levels to L-arginine suggest inhibition or decreased expression of NOS in HBG diabetics. The differences between MBG and HBG diabetics may explain the conflicting reports in literature about the changes in NO levels in early DR.
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