Plasmalogen Levels Are Reduced In Erythrocytes From Patients With Diabetic Retinopathy

Abstract

 

Purpose:

 

Plasmalogens are phospholipids characterized by a vinyl ether bond at the sn-1 position and the preferential esterification of polyunsaturated fatty acids (PUFA) at the sn-2 position of glycerol. We have shown that the lack of plasmalogens leads to retinal hyper-capillarization and to persistent hyaloid arteries (Acar et al, ARVO 2007 E-Abstract 2978). Because we hypothesize that plasmalogens are negative regulators of vascular development, we aimed to check their circulating levels in patients having a retinal pathology with vascular proliferation.

 

Methods:

 

Blood samples were collected by venipuncture from 4 control subjects and 42 patients having proliferative or non-proliferative diabetic retinopathy (DR). Patients were classified according to the stage of DR into minimal, moderate or severe non-proliferative DR, and proliferative DR. Erythrocytes were isolated from total blood samples. Total lipids were extracted, and phospholipids were separated using silica cartridges. The plasmalogen content and the fatty acid composition of erythrocyte phospholipids were determined using capillary column gas chromatography. Individual species of phospholipids, including plasmalogens, were quantified by liquid chromatography coupled with a triple quadrupole mass spectrometry instrument (HPLC-ESI+MS/MS).

 

Results:

 

Gas chromatographic analyzes -that give an overview of the plasmalogen content- did not reveal any difference in the levels of plasmalogens between controls and DR patients (analysis of dimethylacetal derivatives). However, the analysis of individual species of phospholipids by HPLC-ESI+MS/MS showed reduced levels of plasmalogens in patients with DR. Indeed, within the 9 species of choline-plasmalogens that contain PUFA at their sn-2 position, 5 of them were at reduced concentrations in erythrocytes of DR patients. In parallel, the amounts of phospholipids (plasmalogens or conventional phospholipids) esterified with docosahexaenoic acid (DHA) were altered in DR patients.

 

Conclusions:

 

Mechanisms responsible for the reduction in blood levels of plasmalogens and DHA in patients with DR are unknown. Since erythrocyte membrane lipid composition is admitted to reflect the lipid composition of nervous tissues, including the retina, one may suggest that DR patients have altered retinal concentrations in plasmalogens and DHA.

 

Keywords: diabetic retinopathy • lipids • clinical laboratory testing