Identification of a circulating biomarker highly associated to retinal omega-3 polyunsaturated fatty acid content: the BLISAR project

Abstract

Purpose : Numerous studies have pointed out the crucial functions played by omega-3 polyunsaturated fatty acids (PUFAs) in the retina. To date, the assessment of retinal content in omega-3 PUFAs in humans is impossible making the use of systemic fatty acid concentrations a mandatory surrogate of tissue composition. However, blood is a complex fluid in which omega-3 PUFAs are distributed in several compartments that include red blood cells, plasma cholesteryl esters and phosphatidylcholines. In the context of the Biomarkers of LIpid Status And metabolism in Retinal ageing (BLISAR) project, the aim of this work was to determine which of these different blood compartments has the highest predictive power for retinal content in omega-3 PUFAs.

Methods : Retinas, plasma and red blood cells were collected from 46 human donors. Phosphatidylcholines and cholesteryl esters were isolated from total plasma by thin-layer chromatography (TLC). The omega 3 PUFAs content of retinas, red blood cells, plasma cholesteryl esters and plasma phosphatidylcholines was determined by gas chromatography coupled to flame ionization detection (GC-FID). The structural analysis of red blood cells phospholipids was performed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). A statistical analysis based on sparse group partial least squares (sgPLS) was used to identify the blood compartment of interest and further build a prediction model of retinal omega-3 PUFAs concentrations.

Results : Whereas red blood cell lipids and phosphatidylcholines were weakly associated to retinal omega-3 PUFAs, plasma cholesteryl ester fatty acids displayed the highest correlation (r=0.64). The model resulting from the sgPLS analysis and having the lowest prediction error combined the concentration values of 7 circulating species of cholesteryl esters (cross-validated r²=0.38).

Conclusions : This part of the BLISAR project has: i) identified circulating cholesteryl esters as valuable markers of retinal omega-3 PUFAs content, and ii) established a mathematical model that is predictive of retinal omega-3 PUFAs concentrations. Other studies of the BLISAR project were dedicated to the validation of this biomarker in AMD and supplementation conditions.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.