June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Exogenous Retinaldehydes are Anti-oxidants and Correct Photoreceptor Dysfunction in Diabetic Mice In Vivo
Author Affiliations & Notes
  • Robin Roberts
    Anatomy & Cell Biol, Wayne State Univ Sch of Med, Detroit, MI
  • Priya Patel
    Anatomy & Cell Biol, Wayne State Univ Sch of Med, Detroit, MI
  • Ankit Bhatia
    Anatomy & Cell Biol, Wayne State Univ Sch of Med, Detroit, MI
  • Timothy S Kern
    Medicine, Case Western Reserve University, Cleveland, OH
  • Bruce A Berkowitz
    Anatomy & Cell Biol, Wayne State Univ Sch of Med, Detroit, MI
    Ophthalmology, Wayne State University School of Medicine, Detroit, MI
  • Footnotes
    Commercial Relationships Robin Roberts, None; Priya Patel, None; Ankit Bhatia, None; Timothy Kern, None; Bruce Berkowitz, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4281. doi:https://doi.org/
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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)

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Abstract

Purpose: 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.

Methods: 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).

Results: 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.

Conclusions: 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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