Retina and Omega-3

Querques, Giuseppe; Forte, Raimondo

doi:10.1155/2011/748361

Cited by 70 publications

(45 citation statements)

References 96 publications

(105 reference statements)

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“…DHA accounts for a significant fraction of omega-3 fats in the retina, and studies have found links between reduction in DHA with altered retinal function, including in RP [56,57]. This result is consistent with the numerous suggested protective roles of DHA in the retina, including anti-inflammatory, anti-angiogenesis, and anti-neurotoxic mechanisms [58].…”

Section: Metabolite/lipid Imaging Of Retinal Tissue Sections -To Invesupporting

confidence: 77%

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

Wert

Vélez

Vijayalakshmi

et al. 2019

Preprint

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One Sentence Summary: The study shows protein and metabolite pathways affected during neurodegeneration and that replenishing metabolites provides a neuroprotective effect on the retina. Abstract: 244Main Text: 9,039References: 83 AbstractNeurodegenerative diseases are debilitating, incurable disorders caused by progressive neuronal cell death.Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in retinal photoreceptor cell death and progresses to the loss of the entire neural retinal network. We previously found that proteomic analysis of the adjacent vitreous serves as way to indirectly biopsy the neural retina and identify changes in the retinal proteome. We therefore analyzed protein expression in liquid vitreous biopsies from autosomal recessive retinitis pigmentosa (arRP) patients with PDE6A mutations and arRP mice with Pde6ɑ mutations. Proteomic analysis of retina and vitreous samples identified molecular pathways affected at the onset of photoreceptor cell death. Based on affected molecular pathways, arRP mice were treated with a ketogenic diet or metabolites involved in fatty-acid synthesis, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle. Dietary supplementation of a single metabolite, ɑ-ketoglutarate, increased docosahexaeonic acid (DHA) levels, provided neuroprotection, and enhanced visual function in arRP mice. A ketogenic diet delayed photoreceptor cell loss, while vitamin B supplementation had a limited effect. Finally, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) revealed restoration of key metabolites that correlated with our proteomic findings: pyrimidine and purine metabolism (uridine, dihydrouridine, and thymidine), glutamine and glutamate (glutamine/glutamate conversion), and succinic and aconitic acid (TCA cycle). This study demonstrates that replenishing TCA cycle metabolites via oral supplementation prolongs vision and provides a neuroprotective effect on the photoreceptor cells and inner retinal network.

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Section: Metabolite/lipid Imaging Of Retinal Tissue Sections -To Invesupporting

confidence: 77%

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

Wert

Vélez

Vijayalakshmi

et al. 2019

Preprint

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“…It is of interest to note that dietary LPC-EPA markedly increased the omega 3 FAs not only in the brain but also in the retina, where Mfsd2a-mediated uptake is known to play a critical role (16). The protective role of EPA and DHA against retinopathies has been shown by several studies (41)(42)(43). The retina is unique in having very long-chain omega 3 FAs that give rise to pro-homeostatic molecules called elavonoids, which are essential for the integrity of the retinal pigmental epithelial cells (44).…”

mentioning

confidence: 99%

Dietary lysophosphatidylcholine-EPA enriches both EPA and DHA in the brain: potential treatment for depression

Rao

Sugasini

Dasarathi

et al. 2019

Journal of Lipid Research

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The two major long-chain omega 3 FAs in animal tissues are EPA and DHA. Both of these FAs are known to have beneficial effects as anti-inflammatory agents and protect against various metabolic and neurologic diseases. Although the DHA concentration is higher than EPA in most tissues, the brain and retina are unique in having very high levels of DHA but virtually no EPA (1). The major dietary sources of EPA and DHA are fish, fish oil, and krill oil, all of which usually contain more EPA than DHA (2). However, the EPA levels in the brain are not increased significantly following the feeding of fish oil, krill oil, or even ethyl ester of EPA, although other tissues are enriched in both EPA and DHA (3-6). Interestingly, several clinical and preclinical studies showed that dietary EPA is superior to dietary DHA in the prevention and treatment of depression (7-9). It is therefore puzzling how EPA protects against depression without being incorporated appreciably into the brain. To explain this paradox, it has been proposed that the beneficial effects of EPA may result from the suppression of peripheral inflammation or from its hepatic conversion to DHA, rather than from a direct effect on the brain (10). However, the conversion of EPA to DHA cannot explain why dietary DHA does not have similar effects. The lack of enrichment of brain EPA by the dietary EPA has been explained by proposing that EPA is rapidly oxidized by the brain, in contrast to DHA (11,12). This mechanism is supported by kinetic studies with labeled FAs showing the generation of more water-soluble degradation products from EPA, compared with DHA in the brain (10,11). An alternative explanation that has not been explored is that the omega 3 FAs taken up into the brain do not Abstract EPA and DHA protect against multiple metabolic and neurologic disorders. Although DHA appears more effective for neuroinflammatory conditions, EPA is more beneficial for depression. However, the brain contains negligible amounts of EPA, and dietary supplements fail to increase it appreciably. We tested the hypothesis that this failure is due to absorption of EPA as triacylglycerol, whereas the transporter at the blood-brain barrier requires EPA as lysophosphatidylcholine (LPC). We compared tissue uptake in normal mice gavaged with equal amounts (3.3 mol/day) of either LPC-EPA or free EPA (surrogate for current supplements) for 15 days and also measured target gene expression. Compared with the no-EPA control, LPC-EPA increased brain EPA >100-fold (from 0.03 to 4 mol/g); free EPA had little effect. Furthermore, LPC-EPA, but not free EPA, increased brain DHA 2-fold. Free EPA increased EPA in adipose tissue, and both supplements increased EPA and DHA in the liver and heart. Only LPC-EPA increased EPA and DHA in the retina, and expression of brain-derived neurotrophic factor, cyclic AMP response element binding protein, and 5-hydroxy tryptamine (serotonin) receptor 1A in the brain. These novel results show that brain EPA can be increased through diet. Because LPC-EPA increase...

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“…This is in line with the reports that DHA is the most abundant polyunsaturated fatty acid in the brain 30 and that upon crossing the blood-brain-barrier it is rapidly incorporated into phospholipids in particular into phosphatidylethanolamines 31 . Molecular images of DHA in whole-body sections confirm this and also highlight its localization within retina, where DHA is known to play structural and protective roles 32 . We also examined molecular images of lysophosphatidylcholine LysoPC (22:6) or LysoPC-DHA, another storage molecule of DHA (Figure 3b, also more images in METASPACE ).…”

Section: Exploring Spatial Metabolomes On the Levels Of Tissues And Omentioning

confidence: 61%

METASPACE: A community-populated knowledge base of spatial metabolomes in health and disease

Alexandrov

Ovchinnikova²,

Palmer³

et al. 2019

Preprint

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Metabolites, lipids, and other small molecules are key constituents of tissues supporting cellular programs in health and disease. Here, we present METASPACE, a community-populated knowledge base of spatial metabolomes from imaging mass spectrometry data. METASPACE is enabled by a high-performance engine for metabolite annotation in a confidence-controlled way that makes results comparable between experiments and laboratories. By sharing their results publicly, engine users continuously populate a knowledge base of annotated spatial metabolomes in tissues currently including over 3000 datasets from human cancer cohorts, whole-body sections of animal models, and various organs. The spatial metabolomes can be visualized, explored and shared using a web app as well as accessed programmatically for large-scale analysis. By using novel computational methods inspired by natural language processing, we illustrate that METASPACE provides molecular coverage beyond the capacity of any individual laboratory and opens avenues towards comprehensive metabolite atlases on the levels of tissues and organs.

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Retina and Omega-3

Cited by 70 publications

References 96 publications

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

Dietary lysophosphatidylcholine-EPA enriches both EPA and DHA in the brain: potential treatment for depression

METASPACE: A community-populated knowledge base of spatial metabolomes in health and disease

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