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).
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Funding This studies was funded by an RO1EY18395 grant from the National Eye Institute, National Institutes of Health (NIH), USA, to WK, and by unrestricted grant from The Research to Prevent Blindness, USA, to the Department of Ophthalmology.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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