Docosahexaenoic acid uptake and metabolism in photoreceptors: retinal conservation by an efficient retinal pigment epithelial cell-mediated recycling process.

After 18:3 omega 3 is obtained from the diet, it is accumulated by the liver, where it is esterified and temporarily stored as triacylglycerols. As it is required, 18:3 omega 3 is elongated and desaturated to 22:6 omega 3, then released into the circulation with lipoprotein carriers. RPE cells remove the 22:6 omega 3 from the choriocapillaris and subsequently release it to the retina proper. In the frog, all 22:6 omega 3 input to the photoreceptors occurs by way of the RPE cells. After passing through the interphotoreceptor matrix, it is selectively taken into the myoid region of photoreceptor cells where it is immediately activated and esterified onto position 2 (and sometimes also position 1) of a glycerol molecule. Some phospholipids are passed through the endoplasmic reticulum and Golgi apparatus, while others are not. Generally, transport to the outer segments seems to be independent of the Golgi apparatus. Addition to rod outer segments occurs in two ways: i) a general diffuse pathway, probably common to all fatty acids, which rapidly labels the entire outer segment; and ii) a specific dense pathway, utilized only by 22:6 omega 3-containing phospholipids, which become locked into the matrix of disc membranes along with opsin. There appears to be no exchange between these two forms of label. Accumulation of newly synthesized basal discs pushes older, 22:6 omega 3-laden discs apically until the outer segment tips, high in 22:6 omega 3-phospholipids (the dense form of outer segment label), are shed into the RPE cytoplasm. There, as the 22:6 omega 3 fatty acids are released from the disc membranes during degradation, a recycling mechanism immediately directs these essential fatty acids back into the interphotoreceptor matrix, thus conserving this molecule in the retina, and permitting it to be again selectively taken up by the photoreceptors for photomembrane synthesis. The process of 22:6 omega 3 handling and trafficking by the retina is specifically orchestrated around a conservation mechanism that is regulated by the RPE cells and that ensures, through a short feedback loop from the phagosomes to the interphotoreceptor matrix, adequate levels of 22:6 omega 3 for photoreceptors at all times.