Previous studies on the metabolism of polyunsaturated fatty acids in the retinas of miniature poodles had suggested that the essential fatty acid, linolenic acid, having 18 carbon atoms and three double bonds, was not elongated and desaturated to docosahexaenoic acid (DHA) with 2 carbons and six double bonds in the rod outer segments (ROS). This analysis was made 24 hours after intravitreal injection of labeled linolenic acid. Further study revealed that some elongation and desaturation had taken place elsewhere in the retinas. A more detailed study in rats showed that there was rapid conversion of linolenic acid to several of the intermediates in the pathway but that the final desaturation step was extremely slow, as was the appearance of labeled DHA in ROS. Thus, the mammalian retina appears to be capable of converting small amounts of linolenic acid to DHA but is probably dependent on extraocular sources for the DHA needed to replace large amounts of ROS disc membranes, which are uniquely enriched in this fatty acid. Poodles affected with progressive rod-cone degeneration (prcd) have low blood levels of DHA probably because of a defect in the final desaturating enzyme. Several types of retinitis pigmentosa patients also exhibit low blood levels of DHA, which could result in impaired ROS renewal. Attempts to identify the plasma proteins involved in transporting linolenic acid and DHA have revealed that labeled linolenic acid, administered by gavage, first enters the blood bound to very low density lipoprotein which transports it to the liver. After conversion to DHA the labeled fatty acid then appears to be transported by albumin. Identification of the carrier proteins will target candidate genes for studies of inherited retinal degenerations.
