Protective effect of bis-allylic deuterated docosahexaenoic acid (D-DHA) against Light Induced Retinal Degeneration

Abstract

Purpose : Docosahexaenoic acid (DHA) is essential for photoreceptor function and health, therefore retinal DHA depletion is associated with many retinal degenerative diseases such as age-related macular degeneration. However, the multiple cis-double bonds in natural DHA (H-DHA) in the metabolically active retina are highly prone to free radical peroxidation that generates deleterious lipid metabolites that contribute to age-related retinal pathologies. We hypothesize bis-allylic deuterated docosahexaenoic acid DHA (D-DHA) will be more resistant to lipid peroxidation, inhibit light-induced radical lipid peroxidation, and attenuate light-induced retinal degeneration. We therefore determined the protective effect of D-DHA against light-induced oxidative stress in the retina.

Methods : Sprague-Dawley rats were raised on regular lab chow under 25-lux light conditions until 8 weeks of age. The rats were then switched to experimental diets of H-DHA or D-DHA until retinal DHA levels were ~50% or 75%. To determine the protective effect of D-DHA against light stress, we exposed the rats to cool white fluorescent bright light stress (2700-lux for 6 h) and returned them to their normal housing conditions for 1 week after which we determined retinal function by electroretinography (ERG). We examined preservation of retinal structure by H&E staining and further performed immunostaining on retinal sections using 4-Hydroxynonenal (4-HHE) and Carboxyethylpyrrole (CEP) formed from H-DHA under oxidative stress.

Results : We showed that D-DHA replaced H-DHA in the retina in time dependent manner and had no effect on retinal function under no light stress conditions. After light stress, we observed preservation of retinal function as determined by ERG a-wave and b-wave amplitudes in D-DHA fed rats compared to H-DHA fed rats. Histological analyses revealed significant loss of photoreceptor outer nuclear layer in light exposed H-DHA fed rats compared to D-DHA fed rats 1 week after light stress. Our immunohistological data showed high levels of 4-HHE and CEP in H-DHA under oxidative stress compared to D-DHA fed rats.

Conclusions : Deuterium-reinforced DHA preserved retinal structure and function against light-induced retinal degeneration most likely by inhibiting lipid peroxidation. Taken together, our results suggest the dietary D-DHA may be beneficial in attenuating oxidative stress-induced retinal pathologies.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.