Abstract
Purpose:
Recently, it has been shown that a new class of non-dietary polyunsaturated fatty acids (C>26), the very long chain polyunsaturated fatty acids (VLC-PUFAs), are specifically present in vertebrate retina. Deficiency of VLC-PUFAs in retina may be a key factor in macular pathology of age-related macular degeneration (AMD) and dominant Stargardt disease (STGD3). We hypothesize that the n3/n6 LC-PUFA ratios which act as biomarkers in obesity, diabetes and various inflammatory and oxidative stress related disorders such as AMD could influence retinal n3/n6 VLC-PUFA ratios and VLC-PUFA levels. In the present study, serum LC-PUFA levels and n3/n6 LC-PUFA ratios are compared with retinal VLC-PUFA levels and n3/n6 VLC-PUFA ratios of AMD subjects and age-matched control subjects.
Methods:
Human donor eyes (16 AMD and 24 age-matched control subjects) were collected from the Utah Lions Eye Bank, and 6 mm peripheral retinal punches were used for VLC-PUFA analysis. Fatty acid methyl esters were extracted using a standardized method and analyzed by GC-MS (electron ionization mode). Two methods (A and B) were adopted; method A was used to analyze the LC-PUFAs, while method B was used to analyze C24- C36 VLC-PUFAs.
Results:
The levels of LC-PUFAs in serum are in correlation with retinal VLC-PUFAs in AMD subjects (r=0.44, p=0.10) and in age-matched controls (r=0.41, p=0.05). The n3/n6 ratios of LC-PUFA in serum are in correlation with retinal n3/n6 ratios of VLC-PUFA in AMD subjects (r=0.67, p=0.01) and in age-matched controls (r=0.57, p=0.003). The n3/n6 ratios of VLC-PUFA precursors in serum are in significant correlation with the n3/n6 VLC-PUFA ratios in retina of AMD subjects (r=0.55, p=0.04) and age-matched control subjects (r=0.44, p=0.05). The levels of VLC-PUFAs in AMD patients are comparatively lower than the levels in age-matched control patients (0.61% ± 0.11, p=0.006 versus 1.01% ± 0.07, p=0.01).
Conclusions:
Our findings confirm a deficiency of VLC-PUFAs in AMD eyes. The n3/n6 LC-PUFA ratios in serum serve as biomarkers to predict the n3/n6 VLC-PUFA ratios in AMD subjects and also in age-matched control subjects. Diet plays an important role in altering the levels of n3/n6 LC-PUFA ratios in blood which in turn influence the n3/n6 VLC-PUFA ratios and levels in retina with possible benefical macular on macular physiology and protection against degeneration.