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Gennadiy P Moiseyev, Volha Malechka, Rui Cheng, Jianglei Chen, Jian-Xing (Jay) Ma; Treatment of diabetic mice with chromophore improves visual function and decreases oxidative stress and apoptosis in the retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2659. doi: https://doi.org/.
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Recently, we showed that regeneration of 11-cis-retinal chromophore and visual pigments is impaired in the eyes of a type 1 diabetic animal model. Diabetic animal models also showed decreased levels of interphotoreceptor retinoid-binding protein, a component of the visual cycle, responsible for transport of retinol between the RPE and photoreceptors. We hypothesized that vitamin A metabolism in ocular tissues is disturbed in diabetes, and the impaired regeneration of 11-cis-retinal plays a causative role in visual defects in early DR. The purpose of this study was to determine if the delivery of 9-cis-retinal (a chromophore) to the retina and RPE of diabetic mice can alleviate declined electroretinography (ERG) responses, retinal oxidative stress and neuron apoptosis.
Heterozygous male Akita mice with early onset and severe diabetes were used as a genetic model of type 1 diabetes. Hyperglycemia was monitored monthly in the Akita mice. At 3 months of age, Akita mice were treated with 9-cis-retinal containing eye drops for 7 days. Another group of age-matched diabetic mice received the same volume of the vehicle for control. After the treatment, the mice were subjected to analyses of visual function using ERG recording, retinal oxidative stress using immunostaining of an oxidative stress marker 3-nitrotyrosine (3-NT) and retinal neuron apoptosis using the Cell Death Detection ELISA.
Topical administration of 9-cis-retinal significantly increased a-wave amplitude of scotopic ERG responses in Akita mice compared to the vehicle-treated diabetic animals, suggesting that insufficient chromophore plays a causative role in visual dysfunction in early stages of diabetes. The 9-cis-retinal treatment significantly decreased retinal apoptosis in Akita mice, comparing to their respective vehicle controls, Treatment with 9-cis-retinal also reduced 3-NT in the retina of Akita mice.
Our results demonstrate that 9-cis-retinal delivery improves visual function and reduces oxidative stress and apoptosis in the retina of diabetic mice, suggesting that retinal chromophore deficiency plays a causative role in early diabetic retinopathy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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