title: Polyunsaturated very-long-chain C28-C36 fatty acids and retinal physiology.
abstract: Recent studies have established that retinal health depends on the presence of polyunsaturated C28-C36 fatty acids, in addition to docosahexaenoic acid (DHA, C22:6n-3). Initially characterised 20 years ago, these C28-C36 fatty acids are found as sn-1 acyl components of retinal phosphatidylcholines (PCs), which have DHA in the sn-2 position. This unique PC species is found in both rod- and cone-dominant retinas, mainly in the photoreceptor outer segments where the majority of phototransduction reactions take place. In bovine photoreceptor outer segments, this species is a significant component of lipid membranes. Its C28-C36 fatty acids account for 10 mol % of total PC fatty acids. Polyunsaturated C28-C36 fatty acids are synthesised in the retina, in contrast to eicosapentaenoic acid (EPA, C20:5n-3) and DHA which in humans are predominantly of dietary origin. Synthesis of C28-C36 fatty acids appears to be exclusively catalysed by elongase of very-long-chain fatty acids-4 (Elovl4). Mutations in Elovl4 cause Stargardt disease-3, a juvenile autosomal dominant macular degeneration. A mouse genetic model of the disease carries a human pathogenic 5 bp deletion in the mouse Elovl4 gene. It demonstrates early selective deficiency of retinal C28-C36 acyl PCs, followed later by reduced electroretinographic signals and increased accumulation of toxic N-retinylidene-N-retinylethanolamine (A2E).
authors: Department of Ophthalmology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9057, USA.
authors: Anne
authors: A
authors: McMahon
authors: Wojciech
authors: W
authors: Kedzierski
mesh_terms: D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis / Q000502:physiology*; D005544:Forecasting; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D012160:Retina / Q000737:chemistry / Q000502:physiology*
chemical_list: C418975:ELOVL4 protein, human; D005136:Eye Proteins; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins