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William C Gordon, Bokkyoo Jun, Nicolas G Bazan; Phosphatidylcholine (PC) molecular species-containing very long chain polyunsaturated fatty acids (VLC-PUFAs) are altered in AMD. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):13.
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© ARVO (1962-2015); The Authors (2016-present)
Docosahexaenoic acid (22:6) is concentrated in photoreceptors, necessary for vision, and decreased in retinal degeneration including AMD. Ablation of AdipoR1 in mouse attenuates 22:6 uptake/retention, reduces PC-containing VLC-PUFAs, and kills photoreceptors. A higher AMD incidence occurs in women than men (NIH, 65% vs 35%). Also, phospholipid fatty acids (FAs) are more abundant in women (2.31 g/L) than men (1.97 g/L). Thus, we asked if VLC-PUFA PCs are changed in AMD and if they are gender-specific.<br />
Retinas of AMD and normal eyes were OCT imaged and macular and peripheral samples taken. LC/MS/MS analysis to characterize PC-containing VLC-PUFAs (chosen because 22:6 occurs at all sn-2 positions) followed. PC(56:10)/PC(44:12), PC(56:10)/PC(42:10), and PC(56:12)/PC(42:12) ratios were compared with the GLM Procedure (Least Squares Means-Adjustment for Multiple Comparisons: Bonferroni).
Normally, sn-1 PC FAs from 22 carbons (C) to 32C were barely detectable, but 32C and 34C VLC-PUFAs were abundant, with low abundant 36C and 38C FAs. In one AMD sample, the macula was normal but the periphery showed dramatic overall VLC-PUFA decrease and 32C and 34C FAs were reduced far below the low abundant 36C and 38C FAs. This decrease also occurred in other AMD retinas. Ratio analysis revealed no statistical difference between macula-periphery or AMD-normal, but female-male revealed higher values for females (p ≤ 0.007).<br /> <br />
Photoreceptor-specific bioynthesis of 32C and 34C VLC-PUFAs results in a paucity of 24-32C FAs, indicating shorter chain FAs are steps in long chain synthesis; 32C and 34C VLC-PUFA abundance, with some 36C and 38C, indicate end points. AMD VLC-PUFAs are reduced up to 90%, from 32C FAs toward 38C FAs, with 36C and 38C FAs retained the longest, implying VLC-PUFA reduction in AMD occurs as synthesis is impaired. VLC-PUFAs are important only in rods. Thus, PC reduction in AMD may affect survivability of rods. Conversely, peripheral rods may be affected by events triggering AMD, gradually losing ability to synthesize VLC-PUFAs. Female higher ratios indicate increased VLC-PUFAs overall. If 22:6 regulation is decreased, leading to dramatic VLC-PUFA decrease (as in AdipoR1 KO), and female retinas have a higher VLC-PUFA demand, a female AMD bias may occur, with peripheral rods first showing changes in the retinal 22:6/VLC-PUFA lipodome.
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