An inflammatory model of dry eye syndrome using scopolamine

International audience

No consequence of dietary omega-3 polyunsaturated fatty acid deficiency on the severity of scopolamine-induced dry eye

International audience; Purpose:Epidemiological studies suggest that dietary omega-3 polyunsaturated fatty acids (PUFAs) may protect against prevalence of dry eye. This work aimed to evaluate whether a dietary deficiency in omega-3 PUFAs may increase the severity of dry eye in a scopolamine-induced rat model. Methods:Three consecutive generations of Lewis rats were bred under diets deprived of omega-3 PUFAs. Dry eye was experimentally induced by continuous scopolamine delivery in female animals from the third deficient generation and in female Lewis rats fed for three generations with a balanced diet. After 14 days of treatment, the clinical signs of ocular dryness were evaluated in vivo us…

Identification of lipid accumulation in lacrimal gland from NOD mice

International audience; Purpose: : The NOD mouse is an established animal model of the human disease, Sjögren’s syndrome. The lacrimal gland of male NOD mouse becomes significantly infiltrated with inflammatory cells by 12 weeks of age. Dacryadenitis is associated with massive lipid deposition in the lacrimal acinar cells, a process which starts by 6 weeks of age and is accompanied by onset of inflammatory infiltrates. The aim of this study was to identify the lipids that accumulate in lacrimal glands from NOD mice. Methods: : Lacrimal glands were excised from 12-week-old male NOD (n = 8) and BALB/c mice (n = 10). Lipids were extracted and lipid class distribution examined. Then the lipid c…

Decreasing dietary linoleic acid promotes long chain omega-3 fatty acid incorporation into rat retina and modifies gene expression

International audience; Age-related macular degeneration (AMD) may be partially prevented by dietary habits privileging the consumption of ω3 long chain polyunsaturated fatty acids (ω3s) while lowering linoleic acid (LA) intake. The present study aimed to document whether following these epidemiological guidelines would enrich the neurosensory retina and RPE with ω3s and modulate gene expression in the neurosensory retina. Rat progenitors and pups were fed with diets containing low or high LA, and low or high ω3s. After scotopic single flash and 8-Hz-Flicker electroretinography, rat pups were euthanized at adulthood. The fatty acid profile of the neurosensory retina, RPE, liver, adipose tis…

Plasmalogens and cell‐cell communication between retinal glial cells

National audience; Purpose Plasmalogens are glycerophospholipids containing a vinyl‐ether bond at sn‐1 position of their glycerol backbone and polyunsaturated fatty acids (PUFAs) at sn‐2. We have previously shown that plasmalogens are involved in the regulation of perinatal retinal vascular development and particularly in astrocyte template formation (Saab et al, PLoSONE 2012 9(6):e101076). Since retinal Müller cells and astrocytes can communicate through calcium waves and connexin 43‐rich gap junctions, the aim of our study was to determine whether a reduction of plasmalogen levels affects communication between retinal glial cells. Methods Primary Müller cells and astrocyte were isolated f…

Lipid and fatty acid profile of the retina, RPE/choroid and lacrimal gland, and associations with dietary fatty acids in human subjects

Purpose The contribution of dietary lipids to the accumulation of lipids in the retina during ageing and in the course of age related maculopathies remains under debate. Our objective was to establish associations between fatty acid profiles of ocular structures, and adipose tissue as a surrogate for the past dietary intake of the subjects. Methods Lipids and fatty acids were analyzed by tandem thin-layer chromatography-flame ionization detection and gas chromatography-flame ionization detection from the neural retina, RPE/choroid, lacrimal gland and adipose tissue, collected from 19 women and 8 men, aged 59–95 years. Results DHA concentrations in the neural retina were positively associate…

The role of plasmalogens in the photoreactivity of human retinal lipid extracts of different age groups

Purpose: Plasmalogens (PLs) constitute a specific subclass of phospholipids characterized by a vinyl-ether bond in SN-1 position of the glycerol backbone and account for 10% of total phospholipids in the retina, where are considered as sacrificial antioxidants. PLs above 50% of other phospholipids present in the retina contain polyunsaturated fatty acid (PUFA) chain in SN-2 position. In this work we analyzed the influence of PLs on of phospholipids naturally occurring in the human retina (SRL) in a model system and in retinal pigment epithelium cells in vitro. Methods: Lipid composition of human retinal extracts (RLE) has been determined by GC and LC/MS analysis. RLE and SRL with and withou…

Dietary prevention of visual function and cognitive decline by omega-3 polyunsaturated fatty acids in Senescence Accelerated Mouse P8 (SAM P8)

International audience; Purpose: : Neuronal tissues such as the brain and the retina contain elevated amounts of long-chain omega-3 polyunsaturated fatty acids (PUFAs) and particularly docosahexaenoic acid (DHA). DHA concentrations are known to decrease in the aging brain and are associated with cognitive decline. The senescence-accelerated mouse prone 8 (SAM P8) is a mouse model for aging that exhibits deficits in cognitive performances as well as alterations of retinal functionality (ARVO 2004 E-abstract 797). The aim of this study was to evaluate the effects of a dietary supplementation with DHA on mood, cognition and visual functionality of SAM P8 during aging. Methods: : SAM P8 mice we…

Geometry of conjugated double bonds of CLA isomers in a commercial mixture and in their hepatic 20∶4 metabolites

Rats were fed a fat-free diet for 2 wk. After this period, while maintaining the animals on the same diet, the rats were given intragastrically 180 mg per day of a mixture of conjugated linoleic acids (CLA) as triacylglycerols. Gas chromatography mass spectrometry (GC-MS) analyses of this mixture, as well as hydrazine reduction and GC-MS and GC-Fourier transform infrared analyses of the resulting monoenes, revealed the presence of two major isomers, the 9c,11t- and the 10t,12c-18:2 accompanied by smaller amounts of the 8t, 10c and the 11c, 13t-18:2 isomers. Minor quantities of cis,cis and trans,trans conjugated isomers also were detected. The total fatty acid methyl esters from the liver li…

Plasmalogens and cell-cell communication between retinal glial cells

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.; Purpose: Plasmalogens (or ether-lipids) are a particular class of glycerophospholipids characterized by the presence of a vinyl-ether bond at the sn-1 position of the glycerol backbone and by the preferential esterification of polyunsaturated fatty acids (PUFAs) at the sn-2 position. Plasmalogens are found at high concentrations in retinal macroglial cells such as Müller cells and astrocytes. Müller cells and astrocytes are known to communicate by the way of intracellular calcium waves and gap junctions. Connexin 43 is the major protein of these communicating junctions. The aim o…

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

SUMMARYOmega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in epidemiological studies, but the mechanisms by which a n-3 PUFA dietary imbalance affects CNS development are poorly understood. Active microglial engulfment of synaptic elements is an important process for normal brain development and altered synapse refinement is a hallmark of several neurodevelopmental disorders. Here, we identify …

Lipid profile of tenon's capsule in glaucoma patients

International audience; Purpose: To provide data on the lipid profile of the Tenon’s capsule in Human glaucomatous eyes and to establish possible relationships with the short term outcome of filtration surgery. Methods: Fragments of Tenon’s capsule were collected during glaucoma surgery in patients suffering from open angle glaucoma (10 trabeculectomies and 17 non penetrating deep sclerectomies). The lipid profile of the human samples was determined by gas chromatography. A successful outcome after glaucoma surgery was defined by an intraocular pressure (IOP) ≤ 15 mmHg at 6 months without any IOP‐lowering agent. Results: We included 27 patients (12 males, 15 females) with a mean age of 65.5…

Changes in meibomian fatty acids and ocular surface in patients with meibomian gland dysfunction after minocycline treatment

International audience; Purpose:Tear film lipid layer (TFLL) is a very structured layer with essential functions. Its structure is highly dependent on chemical and physical characteristics of lipids composing the TFLL We previously published alterations in the composition of TFLL in patients suffering from meibomian gland dysfunction (MGD). Branched chain fatty acids (BCFA) were significantly increased, suggesting that BCFA may be associated with the disease. The aim of this study was to evaluate the effect of a treatment by oral minocycline associated to lid hygiene versus lid hygiene only on changes in ocular surface abnormalities and in meibomian fatty acid composition in patients suffer…

Lipid and fatty acid profile of the retina, retinal pigment epithelium/choroid, and the lacrimal gland, and associations with adipose tissue fatty acids in human subjects

International audience; Accumulation of lipids within Bruch’s membrane (BrM) and between BrM and retinal pigment epithelium (RPE) accounts for one of the biological changes associated with normal aging and may contribute to the development of age-related maculopathies. The origin of these lipids is still being actively investigated. The relative contribution of plasma lipids and lipids coming from the neural retina remains a matter of controversy. Low-density lipoproteins (LDLs) have been reported to significantly participate in the retina’s lipid supply, after active remodeling within RPE. Meanwhile, RPE expresses the enzymatic machinery for synthesizing lipoprotein-like particles. The obj…

INHIBITION OF FATTY ACID DESATURASES INDrosophila melanogasterLARVAE BLOCKS FEEDING AND DEVELOPMENTAL PROGRESSION

International audience; Fatty acid desaturases are metabolic setscrews. To study their systemic impact on growth in Drosophila melanogaster, we inhibited fatty acid desaturases using the inhibitor CAY10566. As expected, the amount of desaturated lipids is reduced in larvae fed with CAY10566. These animals cease feeding soon after hatching, and their growth is strongly attenuated. A starvation program is not launched, but the expression of distinct metabolic genes is activated, possibly to mobilize storage material. Without attaining the normal size, inhibitor-fed larvae molt to the next stage indicating that the steroid hormone ecdysone triggers molting correctly. Nevertheless, after moltin…

Genetic variability in metabolic and behavioral responses to Western life style: analysis of the transcortin-deficient mouse after high fat diet and chronic stress

National audience

Red blood cell plasmalogens and docosahexaenoic acid are independently reduced in primary open-angle glaucoma

International audience; Among several theories involved in the pathogenesis of primary open-angle glaucoma (POAG), the vascular theory considers the disease to be a consequence of reduced ocular blood flow associated with red blood cell abnormalities. Red blood cell membrane structure and function are influenced by their phospholipid composition. We investigated whether specific lipid entities that may affect the membrane physiology, namely, polyunsaturated fatty acids (PUFAs) and plasmalogens, are modified in POAG and whether these potential variations are related to the stage of glaucoma. Blood samples were collected from 31 POAG patients and 10 healthy individuals. The stage of glaucoma …

Circulating plasmalogens in patients with primary open angle glaucoma

Purpose: Neuronal tissues such as the retina contain high amounts of particular phospholipids named “ether-lipids”. Since abnormal blood levels of ether-lipids have been associated with several neurological disorders, we wanted to check whether ether-lipid levels were modified and associated with the severity of POAG. Methods: Blood samples were collected from 41 healthy subjects and 64 POAG patients. Following lipid extraction from erythrocytes, total phospholipids including ether-lipids were isolated using silica cartridges. The fatty acid profile of phospholipids was determined using capillary column gas chromatography (GC). The individual molecular species of phospholipids and ether-lip…

Causal Link between n-3 Polyunsaturated Fatty Acid Deficiency and Motivation Deficits

International audience; Reward-processing impairment is a common symptomatic dimension of several psychiatric disorders. However, whether the underlying pathological mechanisms are common is unknown. Herein, we asked if the decrease in the n-3 polyunsaturated fatty acid (PUFA) lipid species, consistently described in these pathologies, could underlie reward-processing deficits. We show that reduced n-3 PUFA biostatus in mice leads to selective motivational impairments. Electrophysiological recordings revealed increased collateral inhibition of dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) onto dopamine D1 receptor-expressing MSNs in the nucleus accumbens, a main brain regio…

Plasmalogen depletion in Müller glia alters both Cx43 expression and gap junction intercellular communication with neighbouring astrocytes

International audience

Erythrocyte Phospholipid and Polyunsaturated Fatty Acid Composition in Diabetic Retinopathy

Background: Long chain polyunsaturated fatty acids (LCPUFAs) including docosahexaenoic acid and arachidonic acid are suspected to play a key role in the pathogenesis of diabetes. LCPUFAs are known to be preferentially concentrated in specific phospholipids termed as plasmalogens. This study was aimed to highlight potential changes in the metabolism of phospholipids, and particularly plasmalogens, and LCPUFAs at various stages of diabetic retinopathy in humans. Methodology and Principal Findings: We performed lipidomic analyses on red blood cell membranes from controls and mainly type 2 diabetes mellitus patients with or without retinopathy. The fatty acid composition of erythrocytes was det…

Impact of dietary fatty acids on autophagy in the retina

Impact of diets unbalanced in n-3 polyunsaturated fatty acids on the mouse olfactory function

Nutrition for the Eye: Different Susceptibility of the Retina and the Lacrimal Gland to Dietary Omega-6 and Omega-3 Polyunsaturated Fatty Acid Incorporation

International audience; The purpose of this study was to compare the susceptibility of the retina and the exorbital lacrimal gland to dietary supplies of long-chain omega-3 (omega 3) and omega-6 (omega 6) polyunsaturated fatty acids (LC-PUFAs). Male Wistar rats were fed a 5% lipid diet containing: (1) 10% eicosapentaenoic acid (EPA) and 7% docosahexaenoic acid (DHA), or (2) 10% gamma-linolenic acid (GLA), or (3) 10% EPA, 7% DHA and 10% GLA or (4) a balanced diet deprived of EPA, DHA and GLA for 3 months. Lipids were extracted from plasma phospholipids, retina and exorbital lacrimal gland, and fatty acid composition was determined by gas chromatography. Dietary supplementation with EPA and D…

Determination of fatty acids content, global antioxidant activity and energy value of weed seeds from agricultural fields in France.

18 pages; International audience; The ecological consequences of seed size variation have been studied extensively in plants. Curiously, little attention has been paid to the qualitative and quantitative variation of the seed-stored molecules and on their ecological significance. Here, we analysed the oil content and oil composition of ca. 200 weed seed species from agricultural fields in France based on single seed accessions, concentrating on interspecies differences and ignoring within-species variation. The relationships between seed weight, oil %, fatty acids (FAs) and the energetic value of the seed and its antioxidant properties were also investigated. The antioxidant activity could …

Ether-lipid and docosahexaenoic acid (DHA) levels in erythrocytes of patients with glaucoma

International audience; Purpose: : Neuronal tissues such as the brain and the retina are known to contain elevated amounts of phospholipids with a vinyl-ether double bond (ether-lipids or plasmalogens) as well as high concentrations of long-chain omega-3 polyunsaturated fatty acids (docosahexaenoic acid or DHA). Abnormal blood levels of ether-lipids and DHA have been associated with several neurological disorders such as Alzheimer Disease. Since many observations bring up the idea of pathogenetic similarities between Alzheimer Disease and glaucoma, the aim of our work was to check whether ether-lipid and DHA levels were modified in glaucoma patients. Methods: : Blood samples were collected …

Identification of a circulating biomarker highly associated to retinal omega-3 polyunsaturated fatty acid content: the BLISAR project

International audience

A novel murine model of aging of the human retina

Purpose Accumulation of lipids, and especially of cholesteryl esters, under the retinal pigment epithelium and within Bruch’s membrane is a normal feature of aging and has also been observed in human eyes with age-related maculopathy. Our objective was to evaluate the retinal phenotype of apoB100,LDLR-/- mice, a model for lipid metabolism dysfunction and potentially of aging of the retina. Methods ApoB100,LDLR-/- mice were studied at 7 and 14 months of age by standard scotopic and photopic electroretinography by comparison to control animals. Fundus images were obtained with a confocal SLO (Heidelberg Retina Angiograph). The integrity of the vascular system was investigated by means of fluo…

Retinal enrichment in omega-3 polyunsaturated fatty acids limits choroidal neovascularization

International audience; Purpose: Age-related Macular Degeneration (AMD) is the primary cause of blindness in elderly population of western countries. Prospective epidemiologic studies have reported that omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of progression to advanced AMD, and particularly to the neovascular forms. In this study, we have investigated the beneficial effects of omega-3 PUFA on choroidal neovascularization (CNV) in mice.Methods: Fat-1 mice, endogenously converting omega-6 to omega-3 PUFA, and littermate controls were used at 4 months of age. CNV was induced unilaterally in eye fundus by photocoagulation using a 532-nm laser. Confocal scanning laser ophthal…

The Exorbital Lacrimal Gland Is 100 Times More Susceptible Than the Retina to Dietary Supplies in Long Chain Omega-6 and Omega 3 Polyunsaturated Fatty Acids

International audience; Purpose:: The purpose of this study was to compare the susceptibility of the retina and the exorbital lacrimal gland to dietary supplies in long chain omega-3 (ω3) and omega-6 (ω6) polyunsaturated fatty acids (LC-PUFAs). Methods:: Male Wistar rats were fed for 3 months with a 5% lipid-diet containing either: 1) 10% of EicosaPentaenoic Acid (EPA, ω3) and 7% of DocosaHexaenoic Acid (DHA, ω3), 2) 10% of γ-Linolenic Acid (GLA, ω6), 3) 10% of EPA, 7% of DHA and 10% of GLA or 4) a balanced diet deprived from EPA, DHA and GLA. After three months of feeding, lipids were extracted from the retina and the exorbital lacrimal gland and fatty acid composition was determined by ga…

Comparision of fatty acids in the tear film lipid layer of normal individuals and patients suffering from chronic blepharitis

International audience

Toxicity of Branched-Chain Fatty Acids in Conjunctival Cell Line

International audience; Purpose:: Tear film lipid composition is modified in patients suffering from chronic blepharitis. We previously found that branched chain fatty acids (BCFA) were significantly increased in tears of these patients, suggesting that BCFA may be involved in the disease. The toxicity of different BCFA as potent inducers of apoptosis has already been established in various cell lines but not in the conjunctiva. The aim of this work was to assess the toxic effects of BCFA in cultures of Chang conjunctival cells. Methods:: Chang’s human conjunctival cells were cultured during 4 or 24h with various concentrations of IsoC16 and IsoC20 as BCFA (from 50 to 200µM), by comparison …

Regio- and stereo-selectivity in the induction of peroxisome proliferation by substituted hexanoic acids

Summary Quantitative structure-activity relationship is an effective tool in order to predict drug potency. A similar approach is actually developed for peroxisome proliferation induced by substituted carboxylic acids issued from plasticizer metabolism in rats. The study is focused on acids found in rat urine after adipic diester dosings. Size, location of the substituted group and length of the chain have been studied. 3-D structure has also been taken in account for 2-ethyl hexanoic acids. The results obtained so far demonstrate that peroxisome proliferation potencies of the considered acids are modified according structure changes. At this time location of the group along the chain appea…

Association of a predictor of retinal omega-3 polyunsaturated fatty acids with advanced age-related macular degeneration: the BLISAR project

International audience

Dietary ω3 fatty acids & metabolic syndrome in the rat: consequences on sensitivity and retinal functionality

International audience; Purpose: High fructose diets have been widely used to trigger metabolic syndrome (MetS) in rodents. Insulin resistance is a major risk factor for the development of type 2 diabetes leading in 30 to 40% of the cases to the development of diabetic retinopathy in humans. In the other hand, ω3 fatty acids have been associated with the prevention of MetS. Few studies have been interested in the early changes occurring in the retina after induction of MetS and to potential of ω3 fatty acids to reverse those effects. Methods: 96 male Brown Norway rats (6 weeks of age) were fed for 3 and 8 days with either of the four following diets (n=8 in each group): a regular chow diet …

Response of genetically obese Zucker rats to ciprofibrate, a hypolipidemic agent, with peroxisome proliferation activity as compared to Zucker lean and Sprague-Dawley rats.

Genetically obese Zucker (fa/fa) rats were used as an experimental model to study the effects of hypolipidemic agents on peroxisome proliferation; comparison was made with Zucker lean phenotype (Fa/-) and Sprague-Dawley strain/phenotype. The pharmacokinetics of a single administration of ciprofibrate (1 or 3 mg/kg), appeared to be similar in all strains/phenotypes. After a 2-week oral administration at the same dosages, there were dosage-related increases in hepatocellular peroxisomal yield and in the hepatic enzymes' cyanide-insensitive acyl-CoA oxidase and catalase. The peroxisomal yield was less increased in Zucker than in Sprague-Dawley rats, while the enzyme activities were similarly i…

Decreasing the dietary intake of linoleic acid promotes the efficacy of dietary long chain omega-3 fatty acids to incorporate the rat retina and modifies gene expression

Decreasing the dietary intake of linoleic acid promotes the efficacy of dietary long chain omega-3 fatty acids to incorporate the rat retina and modifies gene expression. annual meeting of the association-for-research-in-vision-and-ophthalmology (ARVO)

Dietary fatty acids and the prevention of Age-related Macular Degeneration: retinal incorporation and beyond

International audience

ApoB100,LDLR-/- mice exhibit reduced electroretinographic response and cholesteryl esters deposits in the retina

International audience; PURPOSE. To evaluate the retinal phenotype of 7- and 14-month-old apoB100,LDLR–/– mice, a relevant animal model of lipid metabolism dysfunction. METHODS. Single-flash electroretinograms were obtained from 7- and 14-month-old apoB100,LDLR–/– and control mice fed a standard diet under both scotopic and photopic conditions. Visual cycle retinoids were analyzed in eyes from dark-adapted mice. Retinal and choroidal vascularization was evaluated with scanning laser ophthalmoscopy. Fatty acids were analyzed in the retina. Esterified and free cholesterol was detected in eye cryosections. RESULTS. Scotopic and photopic b-wave amplitudes were significantly reduced in apoB100,L…

Lipid composition of lacrimal glands in rats: comparison with human lacrimal glands and possible nutritional modulation

International audience; Purpose:: Prostaglandins (PGs) have been found in tears of patients with ocular surface disorders, and are powerful markers of inflammation. The lacrimal gland has been reported to synthesize PGs. Polyunsaturated fatty acids esterified in phospholipids are the precursors of pro- and anti-inflammatory PGs. The aim of this study was to compare the phospholipid content of the lacrimal gland in human and in different rat species. Moreover the changes in fatty acids of the lacrimal glands of Lewis rats were studied after a nutritional intervention. Methods:: Lacrimal glands were excised from Wistar, Sprague-Dawley and Lewis rats (3 month-old) and from Humans 3 to 36 hours…

Saliva lipidome: A new source of sensory perception and eating habits markers?

International audience

Anti-inflammatory effects of GLA and EPA on a scopolamine-induced dry eye rat model

International audience; Purpose:: The aim of this study was to evaluate the potential anti-inflammatory effects of dietary γ-linolenic acid (GLA) and eicosapentaenoic acid (EPA) in a scopolamine-induced dry eye rat model. Methods:: Female Lewis rats were fed with 5%-lipid diets containing 10% of either GLA or EPA. After two months of feeding, we induced dry eye syndrome using scopolamine continuously delivered via osmotic pumps for 2, 10 and 28 days. At the end of the treatment period, we performed fluorescein staining on the cornea. We sacrificed the animals and excised the ocular tissues and the exorbital lacrimal glands. We immunostained MHCII and mucin MUC5AC on ocular sphere cryosectio…

Electroretinographic and retinal lipid modifications in a rat model of glaucoma

International audience

Short-Term Long Chain Omega3 Diet Protects from Neuroinflammatory Processes and Memory Impairment in Aged Mice

Regular consumption of food enriched in omega3 polyunsaturated fatty acids (oméga3 PUFAs) has been shown to reduce risk of cognitive decline in elderly, and possibly development of Alzheimer's disease. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are the most likely active components of oméga3-rich PUFAs diets in the brain. We therefore hypothesized that exposing mice to a DHA and EPA enriched diet may reduce neuroinflammation and protect against memory impairment in aged mice. For this purpose, mice were exposed to a control diet throughout life and were further submitted to a diet enriched in EPA and DHA during 2 additional months. Cytokine expression together with a thoroug…

Long-term intake of Lacticaseibacillus helveticus enhances bioavailability of omega-3 fatty acids in the mouse retina

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. They could also help to prevent or delay the development of retinopathies. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lacticaseibacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helv…

Metabolic syndrome triggered by high-fructose diet favors choroidal neovascularization and impairs retinal light sensitivity in the rat

Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulatio…

Encapsulation de la lutéine et du DHA sous forme d’émulsions sèches : intérêt pour les pathologies rétiniennes

International audience

Modulation of brain PUFA content in different experimental models of mice.

International audience; The relative amounts of arachidonic acid (AA) and docosahexaenoic acid (DHA) govern the different functions of the brain. Their brain levels depend on structures considered, on fatty acid dietary supply and the age of animals. To have a better overview of the different models available in the literature we here compared the brain fatty acid composition in various mice models (C57BL/6J, CD1, Fat-1, SAMP8 mice) fed with different n-3 PUFA diets (deficient, balanced, enriched) in adults and aged animals. Our results demonstrated that brain AA and DHA content is 1) structure-dependent; 2) strain-specific; 3) differently affected by dietary approaches when compared to gen…

Bioavailability of dietary omega-3 DHA and lutein for the retina: results from a preclinical study in mini-pigs with encapsulated nutrients

Purpose: Epidemiological studies support the hypothesis that dietary omega-3 long chain polyunsaturated fatty acids and carotenoids prevent from Age-related Macular Degeneration (AMD). AREDS2 failed to find benefits of omega-3 supplementation on the progression to advanced AMD. However, lower risk progression was reported in AMD patients of the NAT2 study whom omega-3 incorporation in red blood cells and plasma was the highest. Our purpose was to test whether feeding mini-pigs with encapsulated docosahexaenoic acid (DHA) and lutein would promote the bioavailability of the nutrients in plasma and tissues including the retina. Methods: Microparticles containing lutein and DHA were formed by s…

Analyse de la composition en acides gras du film lacrymal chez des patients souffrant de blépharite chronique, de syndrome sec et chez des patients normaux

National audience

Lipid composition of the human eye: are red blood cells a good mirror of retinal and optic nerve fatty acids?

International audience; BACKGROUND: The assessment of blood lipids is very frequent in clinical research as it is assumed to reflect the lipid composition of peripheral tissues. Even well accepted such relationships have never been clearly established. This is particularly true in ophthalmology where the use of blood lipids has become very common following recent data linking lipid intake to ocular health and disease. In the present study, we wanted to determine in humans whether a lipidomic approach based on red blood cells could reveal associations between circulating and tissue lipid profiles. To check if the analytical sensitivity may be of importance in such analyses, we have used a do…

Validation of the use of a circulating biomarker of retinal omega-3 polyunsaturated fatty acids in supplementation conditions: the BLISAR project

Profile of Fatty Acids, Tocopherols, Phytosterols and Polyphenols in Mediterranean Oils (Argan Oils, Olive Oils, Milk Thistle Seed Oils and Nigella Seed Oil) and Evaluation of their Antioxidant and Cytoprotective Activities

Background: The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined. Objective: To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO). Methods: The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant …

Quality of dietary supplements in ophthalmology

International audience; Purpose: A rising number of dietary supplements are available to prevent age–related ocular pathologies such as AMD or dry eye syndrome. The purpose of this work was to evaluate the quality of dietary supplements containing omega–3 polyunsaturated fatty acids in terms of lipid, vitamin E and heavy metals composition. Dietary supplements designed for improving mental well–being were included in this study since they should share some similarities.Methods: Twenty dietary complements were analyzed (6 for dry eye prevention, 4 for AMD prevention and 10 for improving mental well–being). Lipids and lipophilic vitamins were extracted. The distribution of the lipid classes w…

Docosahexaenoic acid protects human RPE cells against oxidative stress via PI3K/Akt m-TOR/p70-p85S6K pathways

Purpose Oxidative Stress (OS) plays a critical role in the pathogenesis of age-related macular degeneration (AMD), especially by targeting the retinal pigment epithelium (RPE). Dietary habits with high consumption of docosahexaenoic acid (DHA) have been shown to prevent the development and evolution of AMD. Nevertheless, it is still unclear how DHA affects AMD. Our study aimed to investigate the involvement of the PI3K/Akt and m-TOR/p70-p85S6K pathways in human RPE cells after induction of OS, and then to assess the effect of DHA in the signaling pathways and in the protection against RPE cell death. Methods For this purpose, we used ARPE-19 cells exposed to the prooxidant agent, tert-butyl…

Effect of growing area on tocopherols, carotenoids and fatty acid composition ofPistacia lentiscusedible oil

International audience; In this investigation, we aim to study, for the first time, the effect of the growing area on tocopherols, carotenoids and fatty acid content of Pistacia lentiscus fixed oil. Fruits were harvested from eight different sites located in the north and the centre of Tunisia. Tocopherols, carotenoids and fatty acid content of the fixed oils were determined. The highest carotenoid content was exhibited by Feija oil (10.57 mg/kg of oil). Oueslatia and Tabarka oils displayed the highest alpha-tocopherol content (96.79 and 92.79 mg/kg of oil, respectively). Three major fatty acids were determined: oleic, palmitic and linoleic acids. Oleic acid was the main fatty acid presenti…

Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition

PMCID: PMC6970973; International audience; Understanding the molecular mechanisms underlying the changes observed during aging is a prerequisite to design strategies to prevent age-related diseases. Aging is associated with metabolic changes, including alteration in the brain lipid metabolism. These alterations may contribute to the development of pathophysiological conditions. Modifications in the gut microbiota composition are also observed during aging. As communication axes exist between the gut microbiota and the brain and knowing that microbiota influences the host metabolism, we speculated on whether age-associated modifications in the gut microbiota could be involved in the lipid ch…

Plasmalogen levels are reduced in erythrocytes from patients with diabetic retinopathy

Plasmalogen levels are reduced in erythrocytes from patients with diabetic retinopathy. annual meeting of the association-for-research-in-vision-and-ophthalmology (ARVO)

Impact of a reduction of plasmalogen levels on Muller cell metabolism

Purpose : Retinopathy of Prematurity (ROP) is the leading cause of blindness in premature children resulting from abnormal vascular development. Previous studies have shown that omega-3 polyunsaturated fatty acids (PUFAs) can modulate physiologic and pathologic angiogenesis. Data from our laboratory suggest that plasmalogens, that are phospholipids that concentrate omega-3 PUFAs, are involved in the regulation of post-natal retinal vascular development through the action of a calcium-independent phospholipase A2 (iPLA2) (Saab et al PLoSONE 2014). In the retina, Müller cells are known to play crucial functions in retinal angiogenesis as well as to be rich in plasmalogens and to express phosp…

Detection of lactobacillic acid in low erucic rapeseed oil--A note of caution when quantifying cyclic fatty acid monomers in vegetable oils.

International audience; The purpose of this work was to identify an unknown component which has been detected during the analysis of cyclic fatty acid monomers (CFAMs) in low erucic acid rapeseed oils (LEAR). A sample of crude LEAR was transformed into fatty acid methyl esters (FAMEs) and hydrogenated using PtO2. The hydrogenated sample was fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC) and the fraction containing the CFAMs transformed into picolinyl esters. Analysing these picolinyl derivatives by gas-liquid chromatography coupled to mass spectrometry (GC-MS) showed that the unknown product observed in LEAR is the 11,12-methylene-octadecanoic acid. This cyc…

RPE/Choroid and Neuroretina Differences in Lipid Profile in Humans, and Possible Correlations to Dietary Lipid Intake

International audience; Purpose: : To provide data on the differences in the lipid profile of the neural retina and RPE/choroid in healthy human eyes, and to establish plausible relationships with dietary fat intake, by comparing the lipid profile of the extra orbital fat. Methods: : Human eyes were collected from 28 human donors. The neural retina was dissected from the RPE/choroid. In 6 donors, the lacrimal gland and a piece of the extra orbital fat were collected. The lipid profile of the human samples was analyzed into classes. Phospholipids and cholesteryl esters were purified from RPE/choroid. The fatty acid composition of the retina, lipid fractions of RPE/choroid, and lacrimal gland…

Docosahexaenoic acid and ether-lipid changes and ERG alterations during retinal ischemia-reperfusion in the rat.

International audience

Oxidation-Induced Increase In Photoreactivity of Bovine Retinal Lipid Extract

Open access original paper Source : 10th EPR Workshop on Applications of EPR in Biology and Medicine, 2016 in Krakow, POLAND.; International audience; The mammalian retina contains a high level of polyunsaturated fatty acids, including docosahexaenoic acid (22:6) (DHA), which are highly susceptible to oxidation. It has been shown that one of the products of DHA oxidation-carboxyethylpyrrole (CEP), generated in situ, causes modifications of retinal proteins and induces inflammation response in the outer retina. These contributing factors may play a role in the development of age-related macular degeneration (AMD). It is also possible that some of the lipid oxidation products are photoreactiv…

Gap junction intercellular communication (GJIC) is regulated by plasmalogens in retinal macroglial cells

International audience

Nutritional n-3 polyunsaturated fatty acids deficiency affects microglia phenotype and brain cytokine production

International audience

A detailed analysis of retinal and retinal pigment epithelium phospholipid species: focus on ether-lipids

International audience

Nutritional omega-3 deficiency and emotional behaviors: a role of CB1R?

National audience

Docosahexaenoic acid and ether-lipids are correlated to ERG alterations during retinal ischemia-reperfusion in the rat

International audience

Dietary docosahexaenoic acid (DHA) protects retinal function against Ischemia-reperfusion in the rat

International audience

Quantitative analysis of fatty acids on choline- and ethanolamine-phospholipids in human ocular and non-ocular tissues by liquid chromatography/tandem mass spectrometry (LC-ESI-MS/MS)

Quantitative analysis of fatty acids on choline- and ethanolamine-phospholipids in human ocular and non-ocular tissues by liquid chromatography/tandem mass spectrometry (LC-ESI-MS/MS). annual meeting of the association-for-research-in-vision-and-ophthalmology (ARVO)