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Bruce A. Berkowitz, Edmund Michael Grady, Nikita Khetarpal, Akshar Patel, Robin Roberts; Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(1):606-615. doi: https://doi.org/10.1167/iovs.14-15687.
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To test the hypothesis that in a mouse model of diabetic retinopathy, oxidative stress is linked with impaired light-evoked expansion of choroidal thickness and subretinal space (SRS).
We examined nondiabetic mice (wild-type, wt) with and without administration of manganese, nondiabetic mice deficient in rod phototransduction (transducin alpha knockout; GNAT1−/−), and diabetic mice (untreated or treated with the antioxidant α-lipoic acid [LPA]). Magnetic resonance imaging (MRI) was used to measure light-evoked increases in choroidal thickness and the apparent diffusion coefficient (ADC) at 88% to 100% depth into the retina (i.e., the SRS layer).
Choroidal thickness values were similar (P > 0.05) between all untreated nondiabetic dark-adapted groups and increased significantly (P < 0.05) with light; this expansion was subnormal (P < 0.05) in both diabetic groups. Apparent diffusion coefficient values in the SRS layer robustly increased (P < 0.05) in a light duration-dependent manner, and this effect was independent of the presence of Mn2+. The light-stimulated increase in ADC at the location of the SRS was absent in GNAT1−/− and diabetic mice (P > 0.05). In diabetic mice, the light-dependent increase in SRS ADC was significantly (P < 0.05) restored with LPA.
Apparent diffusion coefficient MRI is a sensitive method for evaluating choroid thickness and its light-evoked expansion together with phototransduction-dependent changes in the SRS layer in mice in vivo. Because ADC MRI exploits an endogenous contrast mechanism, its translational potential is promising; it can also be performed in concert with manganese-enhanced MRI (MEMRI). Our data support a link between diabetes-related oxidative stress and rod, but not choroidal, pathophysiology.
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