Abstract

Objectives: The results of the DCCT/EDIC revealed a strong association between dyslipidemia and the development of diabetic retinopathy. However, there are no experimental data on retinal fatty acid (FA) metabolism in diabetes. This study determined retinal specific FA metabolism in control and diabetic animals.

Methods: Tissue gene and protein expression profiles were determined by qRT-PCR and western blot in control and STZ diabetic rats at 3-6 weeks of diabetes. Fatty acid profiles were assessed by RP-HPLC, and phospholipid analysis was performed by nESI-MS/MS.

Results: We found a dramatic difference between retinal and liver elongase and desaturase profiles with high elongase and low desaturases gene expression in the retina compared to liver. Elovl4, an elongase expressed in the retina, but not in the liver, showed the greatest expression level among retinal elongases, followed by Elovl2, Elovl1 and Elovl6. Importantly, early stage diabetes induced a marked decrease in retinal expression levels of Elovl4, Elovl2 and Elovl6.

Diabetes-induced downregulation of retinal elongases translated into a significant decrease in total retinal docosahexaenoic acid, as well as decreased incorporation of very long chain polyunsaturated fatty acids, particularly 32:6n3, into retinal phosphatidylcholine. This decrease in n3 PUFA was coupled with inflammatory status in diabetic retina, reflected by an increase in gene expression of pro-inflammatory markers IL-6, VEGF, and ICAM-1.

Conclusions: This is the first comprehensive study demonstrating diabetes-induced changes in retinal FA metabolism. Normalization of retinal FA levels by dietary means or/and modulating expression of elongases could represent a potential therapeutic target for diabetes-induced retinal inflammation.