The essential role of docosahexaenoic acid and its derivatives for retinal integrity

The fatty acid composition of photoreceptor outer segment (POS) phospholipids diverges from other membranes, being highly enriched in polyunsaturated fatty acids (PUFAs). The most abundant PUFA is docosahexaenoic acid (DHA, C22:6n-3), an omega-3 PUFA that amounts to over 50% of the POS phospholipid fatty acid side chains. Interestingly, DHA is the precursor of other bioactive lipids such as elongated PUFAs and oxygenated derivatives. In this review, we present the current view on metabolism, trafficking and function of DHA and very long chain polyunsaturated fatty acids (VLC-PUFAs) in the retina. New insights on pathological features generated from PUFA deficient mouse models with enzyme or transporter defects and corresponding patients are discussed. Not only the neural retina, but also abnormalities in the retinal pigment epithelium are considered. Furthermore, the potential involvement of PUFAs in more common retinal degeneration diseases such as diabetic retinopathy, retinitis pigmentosa and age-related macular degeneration are evaluated. Supplementation treatment strategies and their outcome are summarized.