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Robin Roberts, Priya Patel, Ankit Bhatia, Timothy S Kern, Bruce A Berkowitz; Exogenous Retinaldehydes are Anti-oxidants and Correct Photoreceptor Dysfunction in Diabetic Mice In Vivo. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4281. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
In diabetic mice, treatment with the visual cycle chromophore 11-cis-retinaldehyde corrects rod dysfunction as measured by manganese-enhanced MRI (MEMRI). Yet, recent data has ruled out a visual cycle defect in diabetic mice. Thus, we sought to independently confirm the beneficial properties of retinaldehydes on rod function, and determine if this benefit extends to impaired cone-based visual performance. Since antioxidants prevent diabetes-induced rod photoreceptor calcium channel dysfunction in diabetes, we tested the hypothesis that exogenous retinaldehydes have anti-oxidant activity.
Rod function in 2 mo diabetic mice was evaluated using apparent diffusion coefficient (ADC) MRI to measure light-evoked expansion of subretinal space (SRS) in vivo. Cone-based visual performance was evaluated using optokinetic tracking (OKT). Rod-dominated retinal superoxide production was biochemically measured. Groups were systemically treated with 11-cis-retinaldehyde, 9-cis-retinaldehyde (a chromophore surrogate), or all-trans-retinaldehyde (a retinal precursor of 11-cis-retinaldehyde).
Systemic 11-cis-retinaldehyde treatment corrected diabetes-impairment in light-stimulated SRS expansion (ADC MRI). 11-cis-retinaldehyde or 9-cis-retinaldehyde treatment corrected cone-based visual performance (OKT). 9-cis-retinaldehyde and all-trans-retinaldehyde treatment fully inhibited diabetes-induced rod superoxide generation.
In diabetic mice, impaired rod and cone function can be corrected with acute systemic retinaldehyde treatment. The anti-oxidant properties of exogenous retinaldehydes suggest a likely mechanism by which retinoids exert beneficial effects on rod and cone function in the diabetic retina independent of the visual cycle.
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