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Publication

Oxidative stress and light-evoked responses of the posterior segment in a mouse model of diabetic retinopathy.

Authors Berkowitz BA, Grady EM, Khetarpal N, Patel A, Roberts R Submitted By Bruce Berkowitz on 2/2/2015 Status Published Journal Investigative ophthalmology & visual science Year 2015 Date Published 1/1/2015 Volume : Pages 56 : 606 - 15 PubMed Reference Abstract 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 a-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 Mn(2+). 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.

Investigators with authorship
Name Institution Bruce Berkowitz Wayne State University

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