Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice

Sapieha, Przemysław; Chen, J.; Stahl, Andreas; Seaward, Molly R.; Favazza, Tara L.; Juan, Aimee M.; Hatton, Colman J.; Joyal, J-S; Krah, Nathan M.; Dennison, R. J.; Tang, Jie; Kern, Timothy S.; Akula, James D.; Smith, Lois E.H.

doi:10.1038/nutd.2012.10

Cited by 61 publications

(46 citation statements)

References 45 publications

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“…In the db / db mouse, which develops a disease similar to type 2 diabetes due to leptin receptor deficiency, massive reductions in b-wave amplitude have been recorded at ∼6 months of age (35). These findings coincide with vascular defects, including morphological abnormalities and abnormal leakage.…”

Section: Discussionmentioning

confidence: 99%

Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet–Induced Diabetic Retinopathy

et al. 2016

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Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet–induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat–fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat–fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat–fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease.

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Section: Discussionmentioning

confidence: 99%

Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet–Induced Diabetic Retinopathy

et al. 2016

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“…The biological impact of altering lipid intake is thought to be primarily through modification of membrane microdomain composition and specific receptors. Dietary ω3 to ω6 fatty acids may, therefore, impact retinal function and retinal neovascularization (Connor et al, 2007; Fu et al, 2015; Gong et al, 2015, 2016a, 2016b, 2017; Hård et al, 2013; Rezende et al, 2014; Sapieha et al, 2011, 2012; Shao et al, 2014; Stahl et al, 2010). There is no evidence these essential fatty acids are used for fuel, and without adequate synthetic machinery, it would be surprising if they were not used primarily in other capacities.…”

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

123

110

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“…The ω-3 LCPUFA, docosahexaenoic acid (DHA) and ω-6 LCPUFA, arachidonic acid (AA), are present in retinal neural and vascular cell membrane phospholipids 12 . DHA is present in the retina at a higher concentration (20% of lipids) than in any other tissue, and adequate dietary intake is associated with a reduced risk of ROP, DR and AMD 13–16 . Proliferative retinopathy and neovascular AMD are respectively modeled in the mouse eye by oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) 17, 18 .…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 Oxidase 2C Inhibition Adds to ω-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization

Gong

Edin

et al. 2016

ATVB

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Objective Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal and choroidal neovascularization, but ω-3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of ω-3 LCPUFA on neovascular eye diseases. Approach and Results The mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) were used to investigate pathological angiogenesis in the retina and choroid respectively. The plasma levels of ω-3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and ω-3 LCPUFA derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of ω-3 LCPUFA on retinal and choroidal neovascularization by 30% and 20% respectively. In CYP2C8 over-expressing mice fed a ω-3 LCPUFA diet, montelukast suppressed retinal and choroidal neovascularization by 36% and 39% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C ω-3 LCPUFA-derived active metabolites, increased OIR and CNV in vivo. Exposure to selected ω-3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast. Conclusion Inhibition of CYP2C activity adds to the protective effects of ω-3 LCPUFA on pathological retinal and choroidal neovascularization.

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Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice

Cited by 61 publications

References 45 publications

Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet–Induced Diabetic Retinopathy

Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet–Induced Diabetic Retinopathy

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

Cytochrome P450 Oxidase 2C Inhibition Adds to ω-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization

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