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

Berkowitz, Bruce A.; Grady, Edmund Michael; Khetarpal, Nikita; Patel, Abhishek; Roberts, Robin

doi:10.1167/iovs.14-15687

Cited by 59 publications

(149 citation statements)

References 49 publications

(96 reference statements)

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“…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.…”

Section: Mri Proceduressupporting

confidence: 68%

“…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.…”

Section: Experimental Groupsmentioning

confidence: 99%

“…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.…”

Section: Experimental Groupsmentioning

confidence: 99%

“…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.…”

Section: Mri Proceduresmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Berkowitz

Kern

Bissig

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Diabetes appears to induce a visual cycle defect because rod dysfunction is correctable with systemic treatment of the visual cycle chromophore 11-cis-retinaldehyde. However, later studies have found no evidence for visual cycle impairment. Here, we further examined whether photoreceptor dysfunction is corrected with 11-cis-retinaldehyde. Because antioxidants correct photoreceptor dysfunction in diabetes, the hypothesis that exogenous visual chromophores have antioxidant activity in the retina of diabetic mice in vivo was tested.METHODS. Rod function in 2-month-old diabetic mice was evaluated using transretinal electrophysiology in excised retinas and apparent diffusion coefficient (ADC) MRI to measure light-evoked expansion of subretinal space (SRS) in vivo. Optokinetic tracking was used to evaluate cone-based visual performance. Retinal production of superoxide free radicals, generated mostly in rod cells, was biochemically measured with lucigenin. Diabetic mice were systemically treated with a single injection of either 11-cis-retinaldehyde, 9-cisretinaldehyde (a chromophore surrogate), or all-trans-retinaldehyde (the photoisomerization product of 11-cis-retinaldehyde).RESULTS. Consistent with previous reports, diabetes significantly reduced (1) dark-adapted rod photo responses (transretinal recording) by~18%, (2) rod-dominated light-stimulated SRS expansion (ADC MRI) by~21%, and (3) cone-dominated contrast sensitivity (using optokinetic tracking [OKT]) by~30%. Both 11-cis-retinaldehyde and 9-cis-retinaldehyde largely corrected these metrics of photoreceptor dysfunction. Higher-than-normal retinal superoxide production in diabetes by~55% was also significantly corrected following treatment with 11-cis-retinaldehyde, 9-cis-retinaldehyde, or all-trans-retinaldehyde.CONCLUSIONS. Collectively, data suggest that retinaldehydes improve photoreceptor dysfunction in diabetic mice, independent of the visual cycle, via an antioxidant mechanism.

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Section: Mri Proceduressupporting

confidence: 68%

Section: Experimental Groupsmentioning

confidence: 99%

Section: Experimental Groupsmentioning

confidence: 99%

Section: Mri Proceduresmentioning

confidence: 99%