Dietary 20:4n-6 and 22:6n-3 Modulates the Profile of Long- and Very-Long-Chain Fatty Acids, Rhodopsin Content, and Kinetics in Developing Photoreceptor Cells

Suh, Miyoung; Wierzbicki, A.; Lien, Eric L.; Clandinin, Michael T.

doi:10.1203/00006450-200010000-00017

Cited by 37 publications

(16 citation statements)

References 40 publications

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“…STG3 is an autosomal dominant genetic disorder with deficient VLC-PUFAs associated with macular dystrophy and loss of central vision, suggesting a regional importance of these lipids in the macula. VLC-PUFAs are presumed to improve membrane fluidity and packing density, potentially stabilizing the unique folding pattern of outer segment discs, which may allow adequate shedding of rods and cones photoreceptor outer segments (Agbaga et al, 2010; Suh et al, 2000, 2009). Aging eyes are substantially depleted in VLC-PUFA, and their levels are further reduced in age-related macular degeneration (AMD) (Liu et al, 2010).…”

Section: Retinal Lipid Compositionmentioning

confidence: 99%

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

Joyal

Gantner

Smith

2018

Progress in Retinal and Eye Research

111

110

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Section: Retinal Lipid Compositionmentioning

confidence: 99%

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

Joyal

Gantner

Smith

2018

Progress in Retinal and Eye Research

111

110

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“…Dietary long-chain PUFAs have long been recognized to modify the fatty acid composition of phospholipids in the developing retina (150,151). Gangliosides are sialic acid-containing glycosphingolipids that are present in the outer leaflets of all mammalian plasma membranes, where they participate in recognition and www.annualreviews.org • Nutrition and Lipid Rafts signaling activities.…”

Section: Dietary Gangliosides Polyunsaturated Fatty Acids and Retinmentioning

confidence: 99%

The Nutritional Significance of Lipid Rafts

Yaqoob

2009

Annu. Rev. Nutr.

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The structure, size, stability, and functionality of lipid rafts are still in debate, but recent techniques allowing direct visualization have characterized them in a wide range of cell types. Lipid rafts are potentially modifiable by diet, particularly (but not exclusively) by dietary fatty acids. However, it is not clear whether dietary polyunsaturated fatty acids (PUFAs) are incorporated into raft lipids or whether their low affinity to cholesterol disallows this and causes phase separation from rafts and displacement of raft proteins. This review examines the potential for dietary modification of raft structure and function in the immune system, brain and retinal tissue, the gut, and in cancer cells. Although there is increasing evidence to suggest that membrane microdomains, and their modulation, have an impact in health and disease, it is too early to judge whether modulation of lipid rafts is responsible for the immunomodulatory effects of n-3 PUFA. In addition to dietary fatty acids, gangliosides and cholesterol may also modulate microdomains in a number of tissues, and recent work has highlighted sphingolipids in membrane microdomains as potential targets for inhibition of tumor growth by n-3 PUFA. The roles of fatty acids and gangliosides in cognitive development, age-related cognitive decline, psychiatric disorders, and Alzheimer's disease are poorly understood and require clarification, particularly with respect to the contribution of lipid rafts. The roles of lipid rafts in cancer, in microbial pathogenesis, and in insulin resistance are only just emerging, but compelling evidence indicates the growing importance of membrane microdomains in health and disease.

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“…41,42 The importance of docosahexaenoic acid in modulating visual function and in maintaining a healthy retina remains undetermined. Suh et al 43 demonstrated that supplementing rats with ARA plus docosahexaenoic acid altered the fatty acid composition of developing photoreceptors, elevated the rhodopsin content of the retina, and altered the postbleaching kinetics of rhodopsin. These results indicated that structural changes in components of the retina (ie, increased membrane unsaturation in rod outer segments) are associated with an increased efficiency of rhodopsin function.…”

Section: Commentmentioning

confidence: 99%

Biological Safety Assessment of Docosahexaenoic Acid Supplementation in a Randomized Clinical Trial for X-Linked Retinitis Pigmentosa

Wheaton

Hoffman²,

Locke³

et al. 2003

Arch Ophthalmol

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Background: In a 4-year placebo-controlled trial to elevate blood docosahexaenoic acid levels in patients with X-linked retinitis pigmentosa (XLRP), the goal was to assess the potential benefit of docosahexaenoic acid supplementation in altering disease progression. However, docosahexaenoic acid (22:63) is a highly unsaturated fatty acid and considered a target molecule for free-radical oxidative damage. Thus, nutritional provision of docosahexaenoic acid might lead to an increase in antioxidant stress. Additional concerns, such as decreased platelet aggregation, increased bleeding time, and alterations in lipoprotein cholesterol levels, have been reported in supplementation studies with long-chain polyunsaturates.Objective: To assess the biological safety of long-term docosahexaenoic acid supplementation.Design: Forty-four male patients (mean age, 16 years) enrolled in a randomized, double-masked, clinical trial and received docosahexaenoic acid, 400 mg/d, or placebo. Blood samples were collected every 6 months. Biological safety analysis included fatty acids, vitamin A and E concentrations, antioxidant capacity, platelet aggregation, alanine aminotransferase activity, and lipoprotein cholesterol and triglyceride profiles.Results: Mean plasma docosahexaenoic acid levels were elevated 2.5-fold by supplementation compared with baseline. Patients receiving placebo capsules exhibited no change (P = .35) in plasma docosahexaenoic acid content. All adverse events reported were minor and equivalently distributed between groups. Plasma vitamin A concentrations remained unchanged during the trial. Mean plasma vitamin E concentrations were correlated with age (P = .005), such that as patients with XLRP matured, plasma vitamin E concentrations increased to approach normal values. There was a trend (P =.10) toward lower mean vitamin E concentrations in the docosahexaenoic acidsupplemented group after 4 years. Docosahexaenoic acid supplementation did not compromise plasma antioxidant capacity, platelet aggregation, liver function enzyme activity, or plasma lipoprotein lipid content in patients with XLRP. Conclusion:Long-term docosahexaenoic acid supplementation to patients with XLRP was associated with no identifiable safety risks in this 4-year clinical trial.

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Dietary 20:4n-6 and 22:6n-3 Modulates the Profile of Long- and Very-Long-Chain Fatty Acids, Rhodopsin Content, and Kinetics in Developing Photoreceptor Cells

Cited by 37 publications

References 40 publications

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

The Nutritional Significance of Lipid Rafts

Biological Safety Assessment of Docosahexaenoic Acid Supplementation in a Randomized Clinical Trial for X-Linked Retinitis Pigmentosa

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