Associations of human retinal very long-chain polyunsaturated fatty acids with dietary lipid biomarkers

Abstract

The human retina is well-known to have unique lipid profiles enriched in long-chain polyunsaturated fatty acids (LC-PUFAs) and very long-chain polyunsaturated fatty acids (VLC-PUFAs) that appear to promote normal retinal structure and function, but the influence of diet on retinal lipid profiles in health and disease remains controversial. In this study, we examined two independent cohorts of donor eyes and related their retinal lipid profiles with systemic biomarkers of lipid intake. We found that serum and red blood cell lipids, and to a lesser extent orbital fat, are indeed excellent biomarkers of retinal lipid content and n-3/n-6 ratios in both the LC-PUFA and VLC-PUFA series. Eyes from age-related macular degeneration (AMD) donors have significantly decreased levels of VLC-PUFAs and low n-3/n-6 ratios. These results are consistent with the protective role of dietary n-3 LC-PUFAs against AMD and emphasize the importance of monitoring systemic biomarkers of lipid intake when undertaking clinical trials of lipid supplements for prevention and treatment of retinal disease.

Keywords: age-related macular degeneration; diet and dietary lipids; elongation of very long-chain fatty acids elongase 4; eye; mass spectrometry; nutrition; omega-3 fatty acids; retina.

Fig. 1.

Biosynthetic pathways of VLC-PUFA synthesis from dietary precursors.

Fig. 2.

Correlation of n-3/n-6 LC-PUFA ratios in serum with the n-3/n-6 ratios of VLC-PUFAs in retina (r = 0.91; P < 0.001) (A). Correlation of n-3/n-6 of VLC-PUFA precursor ratios in serum with the n-3/n-6 ratios of VLC-PUFAs in retina (r = 0.76; P < 0.001) (B). Correlation of EPA/AA ratios in serum with the n-3/n-6 ratios of VLC-PUFAs in retina (r = 0.92; P < 0.001) (C). The arrows correspond to data points from an outlier donor who consumed 7 g of fish oil daily for 18 months prior to death.

Fig. 3.

GC/MS chromatograms of LC-PUFAs in the outlier’s serum, normal human serum, and GC/MS standard.

Fig. 4.

GC/MS chromatograms of VLC-PUFAs (C-32 and C-34) in cow retina (GC standard), the outlier’s retina, and a normal human retina.

Fig. 5.

Comparison of retinal VLC-PUFA levels (A) and n-3/n-6 VLC-PUFA ratios (B) in age-matched control eyes versus AMD eyes. (P values were determined by Student’s t-test, * P < 0.05.)

Fig. 6.

Comparative differences in serum lipid profiles of age-matched controls versus AMD subjects. (P values were determined by Student’s t-test; * P < 0.05, ** P = 0.09.)