An inflammatory model of dry eye syndrome using scopolamine

International audience

Lipides, santé et vieillissement DMLA et pathologies oculaires

International audience

A pro-diabetic diet triggers early functional and structural changes in the rat retina

International audience; Purpose : Diabetic retinopathy (DR) is the leading cause of blindness in industrial countries before the age of 50 years. The early consequences of diabetes on the retina are nevertheless poorly known. We therefore aimed at characterizing the early effects of a high fructose and high fat diet on the function and structure of the rat retina. Methods : Male Brown Norway rats (6 weeks of age) were fed for 8 days (n=16), 4 weeks (n=16) and 12 weeks (n=8) with 60% fructose+10% lipid rich diet (HFHF), or a standard chow (n=8). At each time point, intraperitoneal insulin tolerance test (ITT-0.5 U/ml) and intraperitoneal glucose tolerance test (GTT-2g/kg body weight) were ca…

Micronutrition : de la théorie à l'application en clinique

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…

Intérêt des oméga 3 pour la rétine

Genetic variation of the cholesterol 24-hydroxylase (CYP46) gene in patients with agre-related macular degeneration or primary open-angle glaucoma

International audience

Time Course of Inflammation and Apoptosis in a Scopolamine–Induced Dry Eye Rat Model

International audience; Purpose: : Dry eye syndrome is due to tear secretion deficiency or excessive tear evaporation leading to tear film instability. The aim of this study was to evaluate the time course of inflammation and apoptosis in a scopolamine–induced dry eye rat model. Methods: : Osmotic pumps continuously delivering scopolamine (12.5mg/d) were implanted subcutaneously in female Lewis rats for 1, 2, 3, 7, 10, 17 and 28 days. During the treatment, the corneal status was assessed by fluorescein impregnation and tears were collected for prostaglandin E2 (PGE2) immunoassay. At the end of the treatment period, the animals were sacrificed and the ocular tissues and the lacrimal glands w…

Alimentation et vision : entre promotion et protection du vieillissement de la rétine

National audience; La nutrition trouve un écho important dans la recherche translationnelle en ophtalmologie. Au-delà de placer la nutrition au chevet du patient, il s’agit de comprendre en quoi et comment la nutrition participe au fonctionnement de la rétine et à prévenir le développement pathologique. Les nutriments lipophiles occupent une place importante dans cette recherche d’association. Ils peuvent être considérés à la fois comme promoteurs du vieillissement rétinien et comme protecteurs de ses évolutions pathologiques.

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…

Mieux manger pour mieux voir

National audience

The ApoB100,LDLR-/- mouse model as an experimental model to study aging of the retina: focus on autophagy, inflammation and oxidative stress

International audience

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…

What is driving the decision to perform filtering surgery in glaucoma patients?

Purpose: To assess what is driving the decision to perform a filtering procedure in glaucoma patients. Methods: Retrospective study in one single University center. All the indications for filtering glaucoma surgeries (alone or combined with cataract extraction) performed in 2013 by the same surgeon were reviewed. The indications were as follows: clinical evaluation of the optic disc, visual field progression, progression on imaging (OCT), poor tolerance to medical treatment, poor control of intraocular pressure (IOP) and cataract. Results: The filtering surgeries (n = 159) were as follows: 78 trabeculectomies, 45 combined cataract and deep sclerectomy, 24 combined cataract and trabeculecto…

Analysis of the vitreomacular interface in a French population-based study (The MONTRACHET study: Maculopathy, Optic Nerve, nuTRition, neurovAsCular and HEarT diseases)

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…

Lipides et rétine - Aspects biologiques

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

Impact of perinatal high fat diet on metabolic parameters, visual function and behaviour in adulthood

National audience

Ultrastructural changes in the outer retina and retinal pigment epithelium of the apob100,LDLR-/- mouse, a murine model of aging of the human retina

Ultrastructural changes in the outer retina and retinal pigment epithelium of the apob100,LDLR-/- mouse, a murine model of aging of the human retina. annual meeting of the association-for-research-in-vision-and-ophthalmology (ARVO)

High fat-high fructose diet triggered metabolic syndrome and retinal neovascular complications in the rat

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.; Purpose : On the contrary to type II diabetes, the consequences of metabolic syndrome (MetS) in the retina are poorly documented. MetS includes insulin resistance, glucose intolerance, dyslipidemia and abdominal adiposity. Vascular changes are strongly associated to metabolic diseases. Thus, we tested the hypothesis that feeding rats with high fructose (60%) and high fat (10%) would contribute to the development of MetS and neovascular retinal complications.Methods : Male Brown Norway rats (6 weeks of age) were fed with a regular chow diet or a 60% rich fructose+10% lipid-rich di…

In senescence accelerated mouse (SAM) heart, the protective effect of postconditioning is associated with a decrease in oxidative stress

Supplément vol.27, World Congress of Cardiology 2006; International audience; The senescent heart susceptibility to ischemia (I) triggers multiple processes especially oxidative stress but precise mechanisms remain unclear. New animal’s models such as "Senescence Accelerated Mouse" Prone 8 (SAM-P8) and their control (SAM-R1) can be useful for a better understanding of aging process. We studied heart adaptation of these mice to I/reperfusion (R) sequence and a putative cardioprotector effect of post-conditioning (PC). Isolated working mice (8 months) hearts were subjected to a global total ischemia (20 minutes at 38°C), followed by 40 minutes of reperfusion. 4 groups of hearts were constitut…

Retinopathy of prematurity screening: evaluation of a first screening

Purpose: Retinopathy of prematurity (ROP) screening concerns preterm infants born before 32 weeks of amenorrhea and/or weighting less than 1500 grams. First screening occurs usually 4 to 6 weeks after birth and always after 31 weeks of amenorrhea. The purpose of this study was to investigate the number of examinations performed before the first signs of retinopathy, in order to determine the best time for first screening.Methods: This retrospective study enrolled preterm infants born before 32 weeks of amenorrhea and/or weighting less than 1500 grams in the University Hospital of Dijon, France, between 11/15/2012 and 12/31/2013. All preterm babies benefited from a ROP screening by fundus ph…

Mice display cholesterol deposits in the retina and reduced electroretinographic response

International audience

Micronutrition : de la théorie à l'application en clinique

National audience; Les prévisions démographiques s'attendent à un accroissement important de la population âgée et très âgée dans les décennies à venir. La prévalence des pathologies oculaires occupe la deuxième place dans cette frange de la population, laissant entrevoir une réelle explosion du coût social et économique associé à la prise en charge des patients. Pourtant, des données théoriques suggèrent que certains nutriments, en particulier lipophiles, pourraient participer à prévenir les effets du vieillissement sur la rétine et le développement pathologique. Ces hypothèses sont corroborées par des données épidémiologiques qui renforcent l'association entre la consommation d'acides gra…

Effects of 24s-hydroxycholesterol on primary glial Müller cells. New insights on Müller cells function and cholesterol homeostasis in the retina

Purpose: Müller cells are macroglial cells in the retina. These cells express various proteins known to undergo glutamate clearance, which dysfunction may be involved in the loss of retinal ganglion cells (RGC) in the course of glaucoma. In neurons and especially in RGC, 24S-hydroxycholesterol (24SOH) is a metabolite produced by conversion of cholesterol by cholesterol 24S-hydroxylase (CYP46A1). This process participates to cholesterol homeostasis by facilitating the removal of cholesterol from neurons. 24SOH might be a signal molecule ensuring the cross-talk between neurons and glia, and putatively between RGC and glia. The aim of our study was to emphasize the response of primary Müller c…

Lionel Brétillon et son équipe récompensés par la Fondation de France

Le 2 février dernier, au Collège de France, à Paris, Lionel Brétillon, Directeur de l’unité CSGA et Responsable de l’équipe « Œil, nutrition et signalisation cellulaire », a reçu le Prix de la Fondation de l’Œil pour des recherches qui ont mis en évidence le lien entre la consommation d’Omégas 3 et la protection de la rétine de l'œil.Ce prix doté de 50 000 € couronne le travail mené avec son équipe depuis 2004. Ces recherches marquent une étape importante dans la prévention de la dégénérescence maculaire liée à l'âge (DMLA).En tout, 18 équipes de chercheurs ont été primées pour un total de 406 000 euros dédiés à la recherche médicale. Ces équipes ont été soutenues par 11 associations rassem…

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

International audience

Cholesterol metabolism in glaucoma

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

Effect of intravitreal injection of Indocyanine Green, Triamcinolone Acetonide and Trypan Blue on the electroretinographic response of rats

International audience; Purpose:: Indocyanine Green (ICG) and Tripan Blue (TB) are commonly used in macular surgery by making easier the internal limiting membrane (ILM) removing. However, the innocuousness of these dyes is not actually established notably for ICG. Then, several authors proposed the use of triamcinolone acetonide (TA) as an alternative to the use of intraoperative dyes for visualizing the ILM. The purpose of this study was to evaluate the effects of intravitreal injection of ICG, TB and TA on the rat electroretinogram (ERG). Methods:: Three groups of 12-week-old Sprague Dawley rats (n=6) received intravitreal injection in one eye of 0.1mL of either ICG 0.5mg/mL, TB 3mg/mL o…

Gangliosides in the retina: a comparative inventory with brain and other ocular structures

International audience

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

24-(S)-hydroxycholesterol is a potent modulator of cholesterol metabolism in rat retinal Müller glia

International audience

Cholesterol metabolism, autophagy and aging

National audience

Involvement of plasmalogens and iPLA2 in the control of post-natal retinal vascular development in mice

International audience; Purpose: The correct development of retinal blood vessels is essential to ensure vision process through sufficient oxygen and nutrient supplies to the retina. It was shown that polyunsaturated fatty acids (PUFAs) could modulate factors involved in tissue vascularization. A congenital deficiency in ether-phospholipids also termed as "plasmalogens" was shown to lead to abnormal ocular vascularization. Because plasmalogens are considered as reservoirs of PUFAs, we wanted to better understand the mechanisms by which plasmalogens may regulate retinal vascular development through the release of PUFAs by a calcium-independent phospholipase A2 (iPLA2). Methods: Retinal vascu…

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

Alimentation et vision

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 …

Traitements médicaux de la DMLA

National audience

Time course of IOP elevation, electroretinographic changes and retinal ganglion cell loss in a rat model of glaucoma induced by laser

International audience; Purpose: To evaluate the time course of intraocular pressure (IOP) elevation, electroretinographic changes and retinal ganglion cell (RGC) loss in a rat model of glaucoma induced by photocoagulation of the trabeculum and the episcleral and limbal veins. Methods: Male Sprague Dawley rats were used at 6 weeks of age. At least 3 of the episcleral veins, the trabeculum and the limbal veins were photocoagulated with a laser at 532nm (Quantel Medical, Vitra) in one eye of the animals. IOP and electroretinogram (ERG) were monitored every 2 weeks during 11 weeks after photocoagulation. Three months after laser photocoagulation, the RGC population was identified with a 5% Flu…

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

International audience

Les facteurs de risque nutritionnels dans les pathologies oculaires liées à l'âge

National 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 …

Rétine et stress olfactif : du vieillissement à la pathologie

National audience

Intégration centrale de la perception sensorielle associée à l’alimentation

Poster; National audience

Existe-t-il une place pour la micronutrition dans les glaucomes ?

National audience; Lamicronutrition a pris ses marques en ophtalmologie principalement dans la dégénérescence maculaire liée à l'âge (DMLA), mais aussi dans les maladies de la surface oculaire. Pour les glaucomes, le stade actuel est plutôt celui de la réflexion qui permet de construire un rationnel à partir des hypothèses physiopathogéniques des glaucomes. Dans ce court article, nous évoquerons ces hypothèses et nous citerons les études animales et chez l'homme qui existent déjà, en insistant sur le rôle des lipides et des acides gras essentiels.

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

International audience

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…

Role of Oxidative Stress in Aging of the Retina in the ApoB100,LDLR-/- Mouse, a Murine Model of Aging of the Human Retina

In vivo oxydation of [9-14C] cyclic fatty acids derived from linoleic acid in the rat

International audience; Abstract - Heating oils and fats may lead to cyclization of polyunsaturated fatty acids, as for example linolenic acid. Cyclohexenyl and cyclopentenyl fatty acids are subsequently present in some edible oils and these are suspected to induce metabolic disorders. In a previous experiment using [1-14C] labeled molecules, we published that these cyclic fatty acids are beta oxidized to the same extent as linolenic acid, at least for the first cycle of beta oxidation. However, it is possible that the presence of a ring could alter the ability of the organism to fully oxidize the molecule. In order to test this hypothesis, we assessed the oxidative metabolism of cyclic fat…

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

Cholesterol homeostasis and retinal stress in anterior ischemic optic neuropathy

Purpose: Anterior ischemic optic neuropathy (AION) is characterized by acute stress of retinal ganglion cells (RGC). Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in RGC where it may exert neuroprotective properties by preventing from cholesterol accumulation via catalyzing the formation of 24S-hydroxycholesterol. Previous findings hypothesize the housekeeping importance of CYP46A1 in the maintenance of cholesterol in the retina. In order to better understand the role of CYP46A1 in the retina, we aimed to define whether CYP46A1 expression and 24S-hydroxycholesterol levels were modified during RGC stress in AION.Methods: Ninety nine male Sprague Dawley rats were randomized …

Oxysterols Incorporate in Primary Porcine Retinal Pigment Epithelial Cells and Induce Inflammation and Oxidative Stress

International audience; Purpose: : Aging is associated with an accumulation of cholesterol in the Bruch’s membrane. Cholesterol is prone to undergo oxidation and to generate oxysterols that have cytotoxic properties. The aim of this study was to evaluate the effects of oxysterols on cell viability, oxidative stress and inflammation and to measure oxysterol incorporation in primary porcine retinal pigment epithelial (RPE) cell cultures. Methods: : Porcine RPE cells were incubated with oxysterols (24S–hydroxycholesterol, 24OH ; 25–hydroxycholesterol, 25OH and 7–ketocholesterol, 7K) (100µg, 50µM) for 24 and 48h. Cell viability was evaluated by measuring mitochondrial succinate dehydrogenase (S…

Ether-Lipids Are Involved in Retinal Vegf Expression and in Postnatal Hyaloid Vessel Regression

Purpose:Ether-lipids are phospholipids that represent about 13% of retinal lipids and whose exact functions remain unknown. However, the preferential esterification of polyunsaturated fatty acids (PUFAs) at the sn-2 position of ether-lipids and their liberation by an ether-lipid-specific phospholipase A2 suggest their involvement in cell signaling processes. Based on the data showing the persistence of the hyaloid vasculature in ether-lipid-deficient mice (DAPAT-/- mice, Rodemer et al Hum Mol Genet 2003), we further investigated the molecular mechanisms by which ether-lipids may regulate hyaloid vessels regression during post-natal development. Methods:C57BL/6 mice were treated at birth eit…

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

International audience

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…

Rôle de l’alimentation dans le fonctionnement, le vieillissement et les pathologies liées à l’âge de la rétine

International audience

Nutrition and prevention of aging and pathology of the retina - From concept to clinical application

National audience

Plasmalogens in the pathogenesis of glaucomatous optic neuropathy

Neuronal tissues such as the retina contain high amounts of plasmalogens. One of their particularities is to concentrate polyunsaturated fatty acids (PUFA) before releasing them specifically. Several data from our laboratory suggest that plasmalogens are involved in the pathophysiology of primary open angle glaucoma (POAG), the second leading cause of blindness worldwide. The different experiments were carried out on human patients with POAG as well as on rodent models of glaucoma. They concerned either the identification of specific alterations of plasmalogen metabolism, or the efficacy of PUFAs to prevent retinal damage. The results have shown a loss of several circulating plasmalogens in…

Acides gras polyinsaturés de la rétine : ont-ils une origine alimentaire ? Lipid Nutri+

National audience; L’objectif du présent article est de faire le point sur l’origine des acides gras polyinsaturés dans la rétine neurale, en se focalisant en particulier sur le DHA. Nous appuierons notre propos en particulier sur nos données récentes obtenues sur des sujets décédés chez qui la rétine neurale et le couple EPR/choriocapillaire ont été prélevés et analysés pour leur contenu en lipides. Le profil en acides gras du tissu adipeux nous a servi de marqueur de consommation. Nous avons ainsi pu rechercher si les teneurs en AGPI de la rétine neurale sont le reflet des habitudes alimentaires des sujets.

Increased oxidative stress is responsible for ether-lipid loss in the retina of senescence accelerated mouse (SAM)

International audience; Purpose: Ether–lipids represent an important class of retinal phospholipids but their exact functions are still unknown. They might act as antioxidants since the vinyl–ether double bond they contain could be the target for newly formed oxygenated radicals. In this work, we investigated the status of ether–lipids and aldehydes, their oxidative degradation products in the retina of a mouse model for aging, the senescence–accelerated mouse prone 8 (SAM P8), in which we reported a reduction of retinal function following 12 months of age (ARVO 2004 E–abstract 797). We completed this study by evaluating the oxidative stress in the retina. Methods: The quantification of eth…

Supplémentation en acide folique, vitamines B6 et B12 et incidence de la DMLA

National audience

Role of 24-S-hydroxycholesterol in membrane dynamics during retinal gliosis in glaucoma

International audience; Purpose : Glaucoma is a severe and irreversible ocular disease characterized by progressive optic neuropathy with the loss of retinal ganglion cells (RGC). One of the established causes of RGC apoptosis is Müller Glial Cell (MGC) activation, called “retinal gliosis”. MGC are the most numerous glial cells in the retina and one of their roles is to maintain cholesterol homeostasis. A lack or an excess of cholesterol in neurons can cause neuro-degeneration. Cholesterol 24S-hydroxylase (CYP46A1) is present in RGC where it catalyses the formation of 24S-hydroxycholesterol (24S-OHC), and thereby participates to cholesterol elimination. CYP46A1 is overexpressed during glauc…

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

Modulation of lipid membrane organization of Müller Glial Cells (MGC) by 24-(S)-hydroxycholesterol (24-S-OHC) in glaucoma

Modulation of lipid membrane organization of Müller Glial Cells (MGC) by 24-(S)-hydroxycholesterol (24-S-OHC) in glaucoma. Session 3: Nutrition and oxysterols biological activities. ENOR Symposium

Problématiques de la nutrition en ophtalmologie – application à la dégénérescence maculaire liée à l’âge nutrition in ophthalmology – clinical application to age-related macular degeneration

« Let food be your medicine. » This contribution from Hippocrates is still timely addressed, especially in the field of ophthalmology. Observational epidemiology reports close associations between food habits and the risk or prevention of several ocular pathologies such as cataract or Age-related Macular Degeneration (AMD). Anti-oxidant vitamins, minerals and lipids are the nutrients that have been the most widely studied. Interventional epidemiology and experimental works partially corroborated these findings. Unexpectedly, the benefit of long chain omega 3 polyunsaturated fatty acids in the prevention of late AMD was not firmly established in Age-Related Eye Disease Study 2 (AREDS2). Neve…

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…

Dietary superoxide dismutase protects against light-induced retinal oxidative stress in young senescence accelerated mice (SAM)

International audience

Retinas of the Diurnal RodentArvicanthis ansorgeiAre Highly Resistant to Experimentally Induced Stress and Degeneration

International audience; PURPOSE. Environmentally induced stress plays a significant role in retinal degeneration and blindness both in animals and in humans. Among such sources of stress, phototoxicity is well studied and has been shown to lead to photoreceptor-specific loss in a number of species. However, the vast majority of studies have been conducted in nocturnal, albino rod-dominant rat and mouse strains, and the pertinence of such findings to human pathology and cone loss is debatable. The authors examined retinal vulnerability to damage in the diurnal murid rodent Arvicanthis ansorgei, a pigmented species with a large number of cones. METHODS. The authors used established protocols …

Cholesterol homeostasis and retinal stress in anterior ischemic optic neuropathy

International audience

Evaluation of an experimental model of dry eye in the rat

International audience

PRÉDICTION DU CONTENU DE LA RÉTINE EN ACIDES GRAS POLYINSATURÉS OMÉGA-3 À TRAVERS LE DOSAGE DE 7 MOLÉCULES D'ESTERS DE CHOLESTÉROL

La présente invention concerne une méthode de détermination du contenu en acides gras polyinsaturés oméga-3 de la rétine d’un sujet comprenant la détermination de la teneur en au moins un ester de cholestérol dans un échantillon sanguin dudit sujet, le contenu en acides gras polyinsaturés oméga-3 de la rétine étant corrélé à la teneur dudit au moins un ester de cholestérol, ledit au moins un ester de cholestérol étant le cholesteryl 5,8,11,14,17-eicosapentaenoate.

Characterization of cholesterol metabolism in an experimental model of glaucoma in rats

International audience; Glaucoma is a neurodegenerative pathology characterized by retinal ganglion cell death. Cholesterol homeostasis disruption has been implicated in several neurodegenerative diseases such as Alzheimer and Huntington. However, its specific role in the retina and association with glaucoma remain unclear. The aim of this study was to characterize the modifications of cholesterol metabolism occurring during an experimental model of glaucoma in rats. Eight-weeks old male rats were subjected to laser photocoagulation of episcleral veins, limbus and trabecular meshwork to elevate intraocular pressure. At a short (3 days) and a long (2 months) time period post-laser, the retin…

Dietary omega 3 fatty acids and metabolic syndrome in the rat retina: consequences on retinal functionality and complications

Dietary omega 3 fatty acids and metabolic syndrome in the rat retina: consequences on retinal functionality and complications. International society for the study of fatty acids and lipids

Maternal n-3 long chain polyunsaturated fatty acids increase n-3 fatty acids in brain glial cells and retina in the rat and improve rod sensitivity

International audience; Purpose: To evaluate the efficacy of long chain n-3 polyunsaturated fatty acids (LC-PUFA) given to female rats during gestation and lactation on the incorporation of n-3 PUFA in the retina and brain glial cells of the newborn rat, and to evaluate the consequences on the electroretinographic (ERG) response. Methods: Sprague Dawley rats were fed during gestation and lactation with a 20%-lipid rich diet containing 0.75% of EPA and 0.55% of DHA. The fatty acid profile was analyzed in the eyeball and in brain glial cells of the litters sacrificed at birth. The retina and brain glial cell phospholipids were similarly analyzed in 14 day-old rats and in the mothers. Standard…

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…

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…

Prevalence of Age-Related Macular Degeneration in Europe

Manuscript no. 2016-1147 Supplemental material is available at www.aaojournal.org/; International audience; [u]Purpose:[/u] Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. [u]Design:[/u] Meta-analysis of prevalence data. [u]Participants:[/u] A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohor…

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

International audience

Identification and quantification of phosphatidylcholines containing very long chain polyunsaturated fatty acid (VLC-PUFA) in bovine and human retina by liquid chromatography/tandem mass spectrometry

The retina is one of the vertebrate tissues with the highest content in polyunsaturated fatty acids (PUFA). A large proportion of the retinal glycerophospholipids, especially those found in photoreceptor membranes, are dipolyunsaturated molecular species. Among them, dipolyunsaturated phosphatidylcholine molecular species are known to contain very long chain polyunsaturated fatty acids (VLC-PUFA) from the n-3 and n-6 series and having 24 to 36 carbon atoms (C24 to C36) and four to six double bonds. Recent interest in the role of VLC-PUFA arose from the findings that a protein named ELOngation of Very Long chain fatty acids 4 (ELOVL4) is involved in their biosynthesis and that mutations in E…

Effect of dietary omega-3 and omega-6 fatty acids on IOP elevation, electroretinographic changes and retinal ganglion cell loss in a laser-induced rat model of glaucoma

International audience; Purpose:To test the efficacy of dietary omega-3 and omega-6 fatty acids in a rat model of glaucoma induced by laser photocoagulation.Methods:Male Sprague Dawley rats were fed for 3 months with a diet containing either: 1) 17% of omega-3 fatty acids (10% EPA + 7% DHA), 2) 10% of omega-6 fatty acids (as GLA), or 3) a combination of both omega-3 and omega-6 fatty acids (10% EPA + 7% DHA + 10% GLA), by comparison with a control group of animals fed with a standard diet deprived of EPA, DHA and GLA (n=10 in each group). After 3 months of diet, glaucoma was induced in one eye of each animal by laser photocoagulation (532nm) of the episcleral veins, the trabeculum and the l…

Micronutrition et dégénérescence de la rétine

National audience

The contribution of tear osmolarity measurement to ocular surface assessment in contact lens wearers

Purpose: To determine whether tear osmolarity using the TearLabTM Osmolarity System contributes to the assessment of the ocular surface in contact lens (CL) wearers.Methods: Data were collected from 44 CL wearers (28 tolerant and 16 intolerant) and 34 healthy subjects. Every patient underwent a thorough ophthalmic examination and tear osmolarity test, conjunctival impression cytology and meibomian lipid sampling. Symptoms, break-up time (BUT), tear osmolarity, conjunctival expression of HLA-DR and meibomian fatty acid composition were evaluated.Results: Tear osmolarity was significantly higher in the controls compared to tolerant and intolerant CL wearers (p=0.0007). Flow cytometry results …

Le rôle des lipides dans les maladies de l’œil

Le rôle des lipides dans les maladies de l’œil

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

International audience

Associations between erythrocyte and ciliary epithelium phosphatidylcholine concentrations in healthy humans

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

Amélioration de la teneur en acides gras polyinsaturés longue chaîne n-3 dans différentes viandes/chairs, détermination de leurs propriétés nutritionnelles chez un animal modèle et acceptabilité par les consommateurs

Cholestérol et rétine

Article de vulgarisation; 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