Abstract
Purpose :
The main causative factors for diabetic retinopathy are hyperglycemia and dyslipidemia. Decreased serum n3/n6 ratios (omega-3 index) observed in diabetic patients are indicative of chronic inflammation and could be a contributing factor for diabetic retinopathy. n3 fatty acids are not only biologically active molecules, but they also give rise to other biologically active non-dietary molecules such as very long chain-polyunsaturated fatty acids (VLC-PUFAs) and neuroprotectins which can play major roles in pathological processes. VLC-PUFAs are a special class of fatty acids present only in the vertebrate retina that are responsible for membrane fluidity in the photoreceptors. We observed a significant drop in VLC-PUFA levels and alterations to their n3/n6 ratios in retinal punches from patients with diabetic retinopathy, compared to those of diabetic and age-matched controls. We chose to study the effect of n-3 PUFA supplementation on VLC-PUFA levels in two spontaneous diabetic models: heterozygous Ins2Akita (Akita) mice and Nile grass rats. We hypothesize that treatment with VLC-PUFA precursor n3 fatty acids could improve serum adiponectin levels and omega-3 index and retinal n3/n6 VLC-PUFA ratios and levels, thereby slowing retinopathy.
Methods :
Akita and WT (C57B6L) mice (n=6/group) were fed with custom formulated fish oil (2:1v/v, 1.2 g/kg/day) diet for eight weeks. Diabetic Nile grass rats, were fed with fish oil mixed with pellet diet for 8 weeks. Animals were sacrificed, and serum, liver, brain and eye tissues were harvested. Retinas were separated from RPE and used for VLC-PUFA analysis. Using a standardized method, fatty acid methyl esters were extracted and then analyzed by GC-MS.
Results :
After two months of supplementation with n-3 PUFA rich fish oil, there was a significant increase in n-3/n-6 VLC-PUFA ratios in both models compared to diabetic controls who were not fed fish oil. We also observed a decrease in serum blood glucose and an increase in serum adiponectin levels. The fish oil supplemented Akita mice had lower adiponectin levels when compared to control Akita mice.
Conclusions :
Our results indicate that VLC-PUFA levels were lower in diabetes and diabetic retinopathy, suggesting that dietary supplementation with n3 LC-PUFAs may help to prevent progression of diabetes and associated retinopathy
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.