| Authors |
Berkowitz BA, Kern TS, Bissig D, Patel P, Bhatia A, Kefalov VJ, Roberts R
|
| Submitted By |
Bruce Berkowitz on 11/9/2015 |
| Status |
Published |
| Journal |
Investigative ophthalmology & visual science |
| Year |
2015 |
| Date Published |
10/1/2015 |
| Volume : Pages |
56 : 6294 - 303 |
| PubMed Reference |
|
| Abstract |
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.
|
|
|