Change in content, incorporation and lipoxygenation of docosahexaenoic acid in retina and retinal pigment epithelium in canine ceroid lipofuscinosis.

We have examined the metabolism of docosahexaenoic acid (22:6, n-3) in retina and retinal pigment epithelium of normal dogs and those affected with canine ceroid lipofuscinosis (CCL), a hereditary degenerative neurological disorder. In the CCL retina, there was a decrease in 22:6 content in phospholipids, particularly phosphatidylethanolamine. This decrease in 22:6 was compensated by an increase in arachidonic acid (20:4, n-6). In contrast, CCL retinal pigment epithelium had higher levels of 22:6 and lower levels of 20:4 in phosphatidylethanolamine. The in vitro incorporation of radiolabeled 22:6 into glycerolipids of CCL retina and retinal pigment epithelium was increased as compared to control. The major lipoxygenase reaction product of 22:6, (11-hydroxy-4,7,9(trans)13,16,19)-22:6, increased 31% in CCL retina, but not in the retinal pigment epithelium. This is the first report describing alterations in content, incorporation and lipoxygenation of 22:6 in an animal model of a human disease (Batten's disease).