Young, Sarah Phyllis; (1998) The effect of pathological concentrations of phytanic acid on the fatty acid composition, vitamin E concentration and function of membranes of cultured mammalian retinal cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The purpose of this study was to investigate possible mechanisms for the retinal degeneration seen in adult Refsum disease. This is an inherited disorder in which phytanic acid, a dietary branched chain fatty acid, cannot be catabolised and as a result it accumulates in tissues and serum. Phytanic acid has the same structure as the side chain of the tocopherols (vitamin E), and some of the signs and symptoms seen in patients with severe and chronic vitamin E deficiency are similar to those seen in adult Refsum disease. For these reasons it has been suggested that an accumulation of phytanic acid in membranes may interfere with vitamin E function. Alternatively phytanic acid may exert its pathological effect through alteration of membrane composition and structure, thereby affecting membrane functions. These hypotheses were investigated by studying the effect of modulating phytanic acid and α-tocopherol concentrations on the lipid composition and certain functional parameters of retinal cell lines in culture. Methods were established and validated for (i) the supplementation of the cell lines with reproducible concentrations of phytanic acid and α-tocopherol, (ii) the quantification of various membrane components of interest, (iii) the measurement of membrane fluidity and the membrane transport of choline, and (iv) the determination of the susceptibility of altered membranes to in vitro lipid peroxidation. Results showed a) the phospholipid fraction of retinal cells readily incorporated phytanic acid resulting in an altered membrane fatty acid composition b) there was no competition in uptake between phytanic acid and α-tocopherol, c) the incorporation of phytanic acid increased membrane fluidity and the transport of choline, and d) the incorporation of phytanic acid did not appear to affect the susceptibility of membranes to in vitro lipid peroxidation. Taken together these results suggested that phytanic acid did not interfere with the incorporation and function of α-tocopherol in retinal membranes but directly affected retinal membrane composition, structure and function.

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