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Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6294-303. doi: 10.1167/iovs.15-16990.

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

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Department of Anatomy and Cell Biology Wayne State University School of Medicine, Detroit, Michigan, United States 2Department of Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States.
Department of Anatomy and Cell Biology Wayne State University School of Medicine, Detroit, Michigan, United States.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.



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.


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-cis-retinaldehyde (a chromophore surrogate), or all-trans-retinaldehyde (the photoisomerization product of 11-cis-retinaldehyde).


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.


Collectively, data suggest that retinaldehydes improve photoreceptor dysfunction in diabetic mice, independent of the visual cycle, via an antioxidant mechanism.

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