Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy

Abstract

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.

Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic Mice

“…Thus, at the present resolution, we previously demonstrated that MRI can distinguish rod inner segment from outer segment based on the light-evoked expansion of the subretinal space in mice and rats, as well as, for example, (1) inner from outer retina manganese uptake as a function of light, (2) DIL-induced suppression of only inner retinal manganese uptake, and (3) the outer nuclear layer-only tetrameric visual arrestin 1 and its reduction via light-evoked translocation. 28,29,50,51 These examples strongly support our claim that the resolution of MRI is sufficient for extracting meaningful layer-specific functional data in vivo. In all cases, animals were humanely euthanized as detailed in our IACUCapproved protocol.…”

“…At 2 months of age, 20-g male C57Bl/6 mice (Jackson Laboratories, Bar Harbor, ME, USA) were randomly divided into the following groups and were studied after 2 months of diabetes (or age-matched): (1) a non-diabetic control group (wild type [wt]); (2) a diabetic group (D); (3) a Dþ11-cisretinaldehyde group (Dþ11-cis); and (4) a Dþ9-cis-retinaldehyde (Dþ9-cis); note that the ADC MRI data for groups i and ii were previously published (29). Retinaldehydes were delivered systemically.…”

“…Glycated hemoglobin (A1c) was measured from blood collected after each experiment. 6,29 Blood was drawn from the left ventricle, after puncture, into a capillary tube and stored in an Eppendorf tube with a small amount of heparin to prevent coagulation. The blood was kept at 48C until analysis within 1 week following the experiment.…”

“…29 Briefly, all animals were maintained in darkness for at least 16 hours before and during the dark phase of MRI examination. High-resolution anatomical and ADC data were acquired on a 7-T system (ClinScan; Bruker, Ewing Twp., NJ, USA), using a receive-only surface coil (1.0-cm diameter) centered on the left eye.…”

“…5,11,[29][30][31] Thus, we wondered if, as previously suggested by data in ex vivo assays, [32][33][34][35] retinaldehydes might be acting as antioxidants in diabetic mouse retina. If so, this could explain the beneficial impact of systemic retinaldehydes on improving dysfunctional rods in diabetes in vivo.…”