The LDL receptor in the retina: the missing link in aging, the new target in dietary prevention

National audience; Purpose: The discovery of the LDL receptor (LDLR) in 1985 by Brown and Goldstein was awarded by a Nobel Prize. The LDLR has initially been identified for its role in mediating the endocytosis of LDL particles in the vascular endothelium. The deposition of lipids, including cholesterol and cholesteryl esters in Bruch’s Membrane in the one hand, and in the vessel intima in the other hand, is one of the common features of age related macular degeneration (AMD) and cardiovascular disease (CVD). Dietary habits with high intakes of omega 3 long chain fatty acids (LCFA) have been associated with AMD prevention. Similar effects have been demonstrated in CVD prevention. The mechan…

Les actualités du GEMO : partie 1, données récentes sur nutrition et stress oxydatif rétinien

Nutrition lipidique et rétine

Impairment of the wave-amplitudes of the scotopic ERG in rats fed for 21 months with small amounts of trans alpha-linolenic acid

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…

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

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

Involvement of plasmalogens and iPLA2 in the control of post-natal retinal vascular development in the mouse. 16. GEM - 10. GERLI lipidomics meeting: from membranes to pathologies

Polyunsaturated fatty acids and Plasmalogens in diabetics

Purpose Plasmalogens (PLS) are phospholipids characterized by a vinyl ether bond and a preferential esterification of polyunsaturated fatty acids (PUFA). We have previously shown that the lack of PLS leads to retinal hyper-capillarization. We hypothesize that PLS are negative regulators of vascular development, and aimed to check their circulating levels in diabetic patients. Methods Blood samples were collected from 88 patients and 14 control subjects. Among diabetics we had 14 patients without diabetic retinopathy (DR), 12 with a mild non proliferative DR, 12 with a moderate non proliferative DR, 22 with a severe non proliferative DR and 24 with a proliferative DR (PDR). Erythrocytes were…

Plasmalogens in the regulation of retinal vascular development: design of a mouse model with chemical inhibition of IPLA2

Plasmalogens in the regulation of retinal vascular development: design of a mouse model with chemical inhibition of IPLA2. annual meeting of the association-for-research-in-vision-and-ophthalmology (ARVO)

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…

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

International audience

The implication of omega-3 polyunsaturated fatty acids in retinal physiology

International audience; Neuronal tissues such as the retina and the brain are characterized by their high content in phospholipids. In the retina, phospholipids can account for until 80% of total lipids and are mainly composed by species belonging to phosphatidyl-choline and phosphatidyl-ethanolamine sub-classes. Within fatty acids esterified on retinal phospholipids, omega-3 PUFAs are major components since docosahexaenoic acid (DHA) can represent until 50% of total fatty acids in the photoreceptor outer segments.For long time, DHA is known to play a major role in membrane function and subsequently in visual processes by affecting permeability, fluidity, thickness and the activation of mem…

Serum omega-3 fatty acids are not associated with age-related macular degeneration

Revue non indexée dans le JCR.; International audience; Evaluation of: Kabasawa S, Mori K, Horie-Inoue K et al. Associations of cigarette smoking but. not serum fatty acids with age-related macular degeneration in a Japanese population. Ophthalmology 118(6), 1082–1088 (2011). Age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly. in developed countries. Risk factors for AMD are classified into endogenous nonmodifiable. factors, including genetics and environmental factors such as smoking and dietary habits. Both. epidemiological and experimental studies suggest that dietary omega-3 long-chain fatty acids. would participate to prevent from the develo…

New insight into the genetics of age-related macular degeneration in connection with lipid metabolism

Evaluation of: Zerbib J, Seddon JM, Richard F et al. rs5888 variant of SCARB1 gene is a possible susceptibility factor for age-related macular degeneration. PLoS ONE 4(10), e7341 (2009).Age-related macular degeneration (AMD) is the leading cause of visual loss in elderly populations of Western countries. According to demographic forecasts, and owing to the improvement in life expectancy, the number of people suffering from this pathology is expected to dramatically increase in the near future, thereby becoming a significant socioeconomic burden. There has been great progress in defining risk factors for AMD over the last few decades. Beyond advanced age, environmental and genetic factors ha…

Acides gras polyinsaturés oméga-3 et neuroprotection

National audience

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…

Involvement of plasmalogens in post-natal retinal vascular development

Objective: Proper development of retinal blood vessels is essential to ensure 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 "plasmalogens'', was shown to lead to abnormal ocular vascularization. Because plasmalogens are considered to be reservoirs of PUFAs, we wished to improve our understanding of the mechanisms by which plasmalogens regulate retinal vascular development and whether the release of PUFAs by calcium-independent phospholipase A2 (iPLA2) could be involved. [br/] Methods and Results: By characterizi…

Cohen Syndrome-Associated Cataract Is Explained by VPS13B Functions in Lens Homeostasis and Is Modified by Additional Genetic Factors

International audience; Purpose: Cohen syndrome (CS) is a rare genetic disorder caused by variants of the VPS13B gene. CS patients are affected with a severe form of retinal dystrophy, and in several cases cataracts also develop. The purpose of this study was to investigate the mechanisms and risk factors for cataract in CS, as well as to report on cataract surgeries in CS patients.Methods: To understand how VPS13B is associated with visual impairments in CS, we generated the Vps13b∆Ex3/∆Ex3 mouse model. Mice from 1 to 3 months of age were followed by ophthalmoscopy and slit-lamp examinations. Phenotypes were investigated by histology, immunohistochemistry, and western blot. Literature anal…

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…

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…

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…

Actualités en micronutrition : dans la famille oméga-3, je voudrais...

National audience

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

Article publié par l'Organisation nationale interprofessionnelle des graines et fruits oléagineux (Paris, France)

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…

Cholesterol metabolism via cyp46a1 in glaucoma

Cholesterol metabolism via cyp46a1 in glaucoma. International society for eye research (ISER) annual meeting

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

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…

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

National audience

Les propriétés anti-angiogéniques des oméga-3

Les oméga-3 dans la DMLA : quand la science confirme la clinique

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)

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 …

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…

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…

Involvement of plasmalogens and polyunsaturated fatty acids in the pathogenesis of glaucoma

Lipides : qui êtes-vous ?

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

Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down-Regulation of CXCL12-Induced T Cell Migration

Pantethine, a natural low-molecular-weight thiol, shows broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We showed recently that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, wit…

Rev-Erb modulates retinal visual processing and behavioral responses to light

International audience; The circadian clock is thought to adjust retinal sensitivity to ambient light levels, yet the involvement of specific clock genes is poorly understood. We explored the potential role of the nuclear receptor subfamily 1, group D, member 1 (REV-ERB; or NR1D1) in this respect. In light-evoked behavioral tests, compared with wild-type littermates, Rev-Erb(-/-) mice showed enhanced negative masking at low light levels (0.1 lx). Rev-Erb(-/-) mouse retinas displayed significantly higher numbers of intrinsically photosensitive retinal ganglion cells (ipRGCs; 62% more compared with wild-type) and more intense melanopsin immunostaining of individual ipRGCs. In agreement with a…

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…

Plasmalogens, polyunsaturated fatty acids (PUFA), and glaucoma

ERG in retinal Research III (Applications)

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

International audience

Alteration of plasmalogens in erythrocytes of patients with diabetic retinopathy

Purpose Plasmalogens are phospholipids characterized by a vinyl ether bond and the preferential esterification of polyunsaturated fatty acids (PUFA). We have shown that the lack of plasmalogens leads to abnormal retinal vascularisation. Because we hypothesize that plasmalogens are negative regulators of vascular development, we aimed to check their circulating levels in patients having a retinal pathology with vascular proliferation. Methods Blood samples were collected from 4 control subjects and 42 patients having proliferative or non-proliferative diabetic retinopathy (DR). Patients were classified according to the stage of DR. The plasmalogen content and the fatty acid composition of er…

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

RESVEGA, a Nutraceutical Omega-3/Resveratrol Supplementation, Reduces Angiogenesis in a Preclinical Mouse Model of Choroidal Neovascularization

Age-related macular degeneration (AMD) is an eye disease that is characterized by damage to the central part of the retina, the macula, and that affects millions of people worldwide. At an advanced stage, a blind spot grows in the center of vision, severely handicapping patients with this degenerative condition. Despite therapeutic advances thanks to the use of anti-VEGF, many resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether supplementation with Resvega®, a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, a well-known polyphenol in grapes, was able to counteract laser-induced choroidal neovascularizat…

A mouse model of in vivo chemical inhibition of retinal calcium-independent phospholipase A2 (iPLA2).

International audience; Numerous studies have reported the implication of calcium-independent phospholipase A2 (iPLA2) in various biological mechanisms. Most of these works have used in vitro models and only a few have been carried out in vivo on iPLA2(-/-) mice. The functions of iPLA2 have been investigated in vivo in the heart, brain, pancreatic islets, and liver, but not in the retina despite its very high content in phospholipids. Phospholipids in the retina are known to be involved in several various key mechanisms such as visual transduction, inflammation or apoptosis. In order to investigate the implication of iPLA2 in these processes, this work was aimed to build an in vivo model of…

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…

Actualités en micronutrition : micrunotrition, oméga-3 et diabète

Lipid nutrition and eye health

 Revue non indexée dans le JCR.; International audience; According to demographic forecasts, the elderly population will represent a growing part of the developed societies in the near future. Eye diseases are the second most prevalent pathologies after the age of 65 years. Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in western countries. The number of people suffering from ocular pathologies is expected to increase sharply in the near future, becoming a socio-economic burden. Recent data indicate that lipid nutrients may represent new tools in the prevention of eye diseases, and especially AMD.

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…

Electrophysiologie et imagerie rétiniennes chez le rongeur

National audience

In vivo consequences of cholesterol-24s-hydroxylase (CYP46A1) inhibition by voriconazole on cholesterol homeostasis and function in the rat retina

Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol in neurons and participates in cholesterol homeostasis in the central nervous system, including the retina. We aimed to evaluate the consequences of CYP46A1 inhibition by voriconazole on cholesterol homeostasis and function in the retina. Rats received daily intraperitoneal injections of voriconazole (60mg/kg), minocycline (22mg/kg), voriconazole plus minocycline, or vehicle during five consecutive days. The rats were submitted to electroretinography to monitor retinal functionality. Cholesterol and 24S-hydroxycholesterol were measured in plasma, brain and retina by gas chromatography-mass spectrometry. T…

Dietary Lipids, omega-3 fatty acids and AMD

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 …

Acides gras alimentaires oméga-3 : depuis les sources alimentaires jusqu'aux effets bénéfiques pour la rétine

Comparative study of serine-plasmalogens in human retina and optic nerve: identification of atypical species with odd carbon chains

International audience; The objective of this work was to detect and identify phosphatidylserine plasmalogen species in human ocular neurons represented by the retina and the optic nerve. Plasmalogens (vinyl-ether bearing phospholipids) are commonly found in the forms of phosphatidylcholine and phosphatidylethanolamine in numerous mammalian cell types, including the retina. While their biological functions are still unclear, the alteration of cellular plasmalogen content has been associated with several human disorders such as Rhizomelic Chondrodysplasia Punctata Type 2 and Primary Open-Angle Glaucoma.By using liquid-chromatography coupled to high resolution and tandem mass spectrometry, we…

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

International audience

Cholesterol metabolism, autophagy and aging

National 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…

Fructose diet induced short-term impairment of cone sensitivity and gene expression in rat retina

National audience; Abstract: Purpose A high fructose diet has been widely used to trigger insulin resistance in rodent; insulin resistance is one of the major risk factor for the development of type 2 diabetes. Thirty to 40% of diabetic patients develop diabetic retinopathy. In this study, we aimed to evaluate the short-term effect, at 1, 3, 5, 8 days, of a 60% fructose diet, on photoreceptor sensitivity and gene expression in the retina of Brown Norway rats. Methods: Flicker electroretinograms (8Hz) were recorded under anesthesia, from both eyes simultaneously in order to study sensitivity of photoreceptors. Then, rats were euthanized and enucleated. Retinae and posterior poles were collec…

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

Plasmalogens in the retina: From occurrence in retinal cell membranes to potential involvement in pathophysiology of retinal diseases

Plasmalogens (Pls) represent a specific subclass of glycerophospholipids characterized by the presence of a vinyl-ether bond at the sn-1 position of glycerol. Pls are quantitatively important in membranes of neuronal tissues, including the brain and the retina, where they can represent until almost two-third of ethanolamine glycerophospholipids. They are considered as reservoirs of polyunsaturated fatty acids as several studies have shown that arachidonic and docosahexaenoic acids are preferentially esterified on Pls when compared to other glycerophospholipids. Reduced levels of Pls were observed in a number of neurodegenerative disorders such as glaucoma, the second leading cause of blindn…

Circulating markers of retinal and optic nerve lipids

Purpose Blood lipids are frequently used as a surrogate of lipid composition of peripheral tissues. Even if it is well accepted, such a relationship has never been clearly demonstrated for the eye. The aim of this study was to determine in human samples whether a lipidomic approach based on red blood cells could reveal associations between circulating and ocular lipid profiles. Methods Red blood cells, retinas and optic nerves were collected from 9 human donors. The lipidomic analyses on these tissues were done by both, gas chromatography and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS/MS). Results Gas chromatographic approach did not show…

Plasmalogens, erythrocyte deformability, and retinal vascular development

Rétine et lipides : de l'analyse à la physiopathologie

Revue; Rétine et lipides : de l'analyse à la physiopathologie. Colloque du Collège National de Biochimie-Biologie Moléculaire Médicale (CNBBMM)

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…

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 l…

Assessment of environmental AMD risk factors in a population of patients suffering from stroke and myocardial infarction

International audience; Purpose: Stroke and myocardial infarction are common diseases occurring in patients suffering from Age Macular Degeneration (AMD). We assessed the rate of AMD and AMD risk factors in patients suffering from recent stroke or myocardial infarction. Methods: Patients suffering from a recent stroke or myocardial infarction (less than 1 month) benefited from a thorough ophthalmic examination with the following measurements and evaluations: visual acuity, intraocular pressure, fundus photography, Raman spectroscopy and macular OCT. In the same time a food questionnaire was dispensed. Finally, blood samples to measure fatty acids and lutein were performed. Results: 74 patie…

Micronutrition et DMLA : d'où vient cette idée

Polyunsaturated fatty acids and plasmalogens in diabetics

PurposePlasmalogens are phospholipids characterized by a vinyl ether bond and a preferential esterification of polyunsaturated fatty acids (PUFA). We have previously shown that the lack of plasmalogens leads to retinal hyper-capillarization. We hypothesize that plasmalogens are negative regulators of vascular development, and aimed to check their circulating levels in diabetic patients with a retinopathy. MethodsBlood samples were collected from 88 patients and 14 control subjects. Among diabetics we had 14 patients without diabetic retinopathy (DR), 12 with a mild non proliferative DR, 12 with a moderate non proliferative DR, 22 with a severe non proliferative DR and 24 with a proliferativ…

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

International audience

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

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 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. After 3 months of diet, glaucoma was induced in one eye of the animal by laser.IOP was regularly measured and the retinal function was evaluated by electroretinography (ERG) for 3 months. At the end of the experiment, …

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 …

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)

Actualités en micronutrition : piste du cholestérol … vers un modèle animal de DMLA ?

In vivo consequences of cholesterol-24S-hydroxylase (CYP46A1) inhibition by voriconazole on cholesterol homeostasis and function in the rat retina

International audience; Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol in neurons and participates in cholesterol homeostasis in the central nervous system, including the retina. We aimed to evaluate the consequences of CYP46A1 inhibition by voriconazole on cholesterol homeostasis and function in the retina. Rats received daily intraperitoneal injections of voriconazole (60 mg/kg), minocycline (22 mg/kg), voriconazole plus minocycline, or vehicle during five consecutive days. The rats were submitted to electroretinography to monitor retinal functionality. Cholesterol and 24S-hydroxycholesterol were measured in plasma, brain and retina by gas chromatog…

Intégration centrale de la perception sensorielle associée à l’alimentation

Poster; National audience

Consequences of dietary omega-3 polyunsaturated fatty acid deficiency on retinal function and intraocular pressure in the rat

Purpose Omega-3 polyunsaturated fatty acids (ω3) are key components in nervous structures but their dietary intakes in the overall population are often below nutritional requirements. A chronic deficiency in ω3 is recognized to be associated with functional impairment of the retina. At the opposite, ω3 supplementation is associated with a reduced risk for AMD. The consequences of ω3 deficiency on other eye structures than the retina, such as ciliary bodies, are scarce. The purpose of our study was to compare the response of the retina and ciliary bodies to dietary ω3 deficiency in terms of fatty acid profile and eye functionality. Methods Two successive generations of Lewis rats (G1 and G2)…

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

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…

Early adaptive response of the retina to a pro-diabetogenic diet: Impairment of cone response and gene expression changes in high-fructose fed rats

The lack of plasticity of neurons to respond to dietary changes, such as high fat and high fructose diets, by modulating gene and protein expression has been associated with functional and behavioral impairments that can have detrimental consequences. The inhibition of high fat-induced rewiring of hypothalamic neurons induced obesity. Feeding rodents with high fructose is a recognized and widely used model to trigger obesity and metabolic syndrome. However the adaptive response of the retina to short term feeding with high fructose is poorly documented. We therefore aimed to characterize both the functional and gene expression changes in the neurosensory retina of Brown Norway rats fed duri…

La rétine en recherche appliquée

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

Place de l'électrophysiologie dans la recherche ophtalmologique chez l'animal

Actualités en micronutrition : Biodisponibilité des acides gras alimentaires

Electroretinographic and retinal lipid modifications in a rat model of glaucoma

International audience

Peroxydation in vivo et in vitro des acides gras polyinsaturés

It is well admitted that polyunsaturated fatty acids are the most sensitive fatty acids to oxidative damage because of their high number of double bonds. This concept could not be confirmed by in vitro, animal, or human studies since unexpected or even contradictory results were obtained. The explanation of that is probably related to the methods evaluating lipid peroxidation whose relevance is not always established, but especially to movements of polyunsaturated fatty acids within lipoproteins that results in their protection. This short review aims to discuss the main results related to this topic.

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…

Actualités en micronutrition : Nouveautés sur la lutéine

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…

Comparative study of post-natal retinal vascular development in mice models of iPLA2 inhibition and plasmalogen deficiency

Purpose: Plasmalogens are particular phospholipids characterized by the presence of a vinyl-ether bond and of a polyunsaturated fatty acid (PUFA) at sn-1 and sn-2 positions of glycerol, respectively. Even if the plasmalogen content of organs and tissues is well documented, their biological functions are still enigmatic. Plasmalogen deficiency in DAPAT-/- mice leads to developmental abnormalities in retinal vasculature (Acar et al, ARVO 2007 E-Abstract 2978) and to persistent hyaloïd arteries. We hypothesize that plasmalogens regulate retinal vascular development through the liberation of PUFA by a plasmalogen-specific calcium-independent phospholipase A2 (iPLA2). We have performed a compara…

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…

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…

Intraocular pressure and central corneal thickness in an old French population: The MONTRACHET study

Purpose: To describe the distribution of intraocular pressure (IOP) and central corneal thickness (CCT) in an old French population. Methods: About 9000 individuals 65 years and older were included in the 3C cohort study since 1999 in 3 French cities (Bordeaux, Dijon and Montpellier). In Dijon, an additional ophthalmic examination was performed 10 years after the initial inclusions to assess the relation between systemic age-related diseases and eye diseases in the MONTRACHET Study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases). In this population-based stuy a thorough eye examination and a questionnaire were undertaken in each participant. Intraocular pressure (IOP) w…

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…

Characterization of plasmalogens in retinal glial cells

Purpose: Plasmalogens (or ether-lipids) constitute a particular class of glycerophospholipids that are 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. Although their exact functions remain enigmatic, previous data from our laboratory suggest that plasmalogens play crucial functions during retinal vessel development by affecting astrocyte template formation (Saab et al PLoSONE 2014;9(6):e101076). The aim of this study was to better characterize plasmalogens in the retina and to determine which cells are responsible for plasmalogens production w…

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…

Combined effects of aging and a pro-diabetic diet on retinal function in a murine model of aging of the human eye

 ; Purpose: Improvement of life expectancy and changes in the dietary behaviour of developed populations are accompanied with the prevalence of diabetes and age-related ocular pathologies. Aging of the retina is characterized by accumulation of lipids at the basement of the retinal pigment epithelium - Bruch’s membrane complex.Meanwhile increased oxidative stress is one of the features of aging and diabetes. A fructose-rich diet induces insulin resistance and hypertriglyceridemia, mimicking diabetes. The goal of our study was to evaluate the effects of a pro-diabetic fructose-enriched diet on the retinal function of the ApoB100,LDLR-/- mice, a murine model of aging of the human eye. Methods…

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…

Subretinal drusenoid deposits in the elderly in a population-based study (the Montrachet study: Maculopathy, Optic Nerve, nuTRition, neurovAsCular and HEarT diseases)

International audience

O32 Le syndrome métabolique induit par un régime enrichi en fructose est promoteur d’un développement néovasculaire et d’altérations fonctionnelles dans la rétine

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…

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…

Exploration of CYP27A1 function in eye cholesterol signaling between glia and neurons in Drosophila.

Dietary polyunsaturated fatty acids reduce retinal stress induced by an elevation of intraocular pressure in rats.

International audience; N-6 and n-3 polyunsaturated fatty acids (PUFAs) have been shown to prevent tissue release of inflammatory molecules. We have shown that a combination of n-6 and n-3 PUFAs is more efficient than single supplementations on the long-term consequences of intraocular pressure elevation. We hypothesized that such an association is also more effective during early retinal stress by modifying retinal proinflammatory prostaglandin and cytokine productions. Rats were supplemented for 3 months with n-6 PUFAs, n-3 PUFAs, or both n-6 and n-3 PUFAs. After 3 months, a surgical elevation of intraocular pressure was induced. Retinal morphometry and glial cell activation were evaluate…

Que peut nous apprendre le pharmacien ?

Dietary polyunsaturated fatty acids, intraocular pressure, and glaucoma

Abstract Glaucoma is a progressive optic neuropathy and is the second leading cause of blindness worldwide. Estimations predict that nearly 80 million people will be affected by the disease in 2020. Increased intraocular pressure (IOP) has been recognized as a major risk factor for developing glaucoma. Although IOP-lowering agents have been shown to be effective for decreasing the progression of glaucoma, extensive research has been done to identify modifiable lifestyle factors involved in the pathogenesis of this disease. Among these factors, dietary lipids and particularly dietary polyunsaturated fatty acids (PUFAs) represent a promising approach. The aim of this chapter is to summarize t…

Acides gras polyinsaturés et oeil : données issues du congrès de l'ARVO 2007

National audience

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

Identification and quantification of phosphatidylcholines containing very-long-chain polyunsaturated fatty acid in bovine and human retina using 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 retinal phospholipids, especially those found in photoreceptor membranes, are dipolyunsaturated molecular species. Among them, dipolyunsaturated phosphatidylcholine (PC) molecular species are known to contain very-long-chain polyunsaturated fatty acids (VLC-PUFA) from the n-3 and n-6 series having 24-36 carbon atoms (C24-C36) and four to six double bonds. Recent interest in the role played by VLC-PUFA arose from the findings that a protein called elongation of very-long-chain fatty acids 4 (ELOVL4) is involved in their biosynthesis and that mutations in the ELOVL…

Incorporation of lutein and docosahexaenoic acid from dietary microalgae into the retina in quail

Abstract Lutein and docosahexaenoic acid (DHA) are associated with the prevention of age-related macular degeneration (AMD). Since microalgae are potent natural sources of these nutrients, their nutritional value should be evaluated based on the bioavailability of lutein and DHA for the retina via the plasmatic compartment. In this study, quail were fed for 5 months either with a diet supplemented or deprived with microalgae rich in lutein and DHA. In the microalgae-fed group, the retinal concentrations of lutein and zeaxanthin gradually increased whereas in plasma, these compounds started to increase from the first month of supplementation. We also observed a significant increase in retina…

24S-hydroxycholesterol and cholesterol-24S-hydroxylase (CYP46A1) in the retina: from cholesterol homeostasis to pathophysiology of glaucoma.

http://www.sciencedirect.com/; International audience; Free cholesterol is the predominant form of cholesterol in the neural retina. The vertebrate neural retina exhibits its own capacity to synthesize cholesterol and meets its demand also by taking it from the circulation. Defects in cholesterol synthesis and trafficking in the neural retina has detrimental consequences on its structure and function, highlighting the crucial importance of maintaining cholesterol homeostasis in the retina. Our purpose was to give a review on the functioning of the retina, the role of cholesterol and cholesterol metabolism therein, with special emphasis on cholesterol-24S-hydroxylase (CYP46A1). Similar to th…

Implication of 24-S-hydroxycholesterol in Muller glial cell's membrane dynamics in the rat.

Implication of 24-S-hydroxycholesterol in Muller glial cell's membrane dynamics in the rat.. Association-for-Research-in-Vision-and-Ophthalmology (ARVO)

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

Nutrition for the eye: last news from ARVO 2008 meeting. Part 1: fundamental data

National 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

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…

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…

Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding

Epidemiological observations report an increase in fat consumption associated with low intake of n-3 relative to n-6 polyunsaturated fatty acids (PUFAs) in women of childbearing age. However, the impact of these maternal feeding habits on cognitive function in the offspring is unknown. This study aims to investigate the impact of early exposure to a high-fat diet (HFD) with an unbalanced n-6/n-3 PUFAs ratio on hippocampal function in adult rats. Furthermore, we explored the effects of perinatal HFD combined with exposure to HFD after weaning. Dams were fed a control diet (C, 12% of energy from lipids, n-6/n-3 PUFAs ratio: 5) or HFD (HF, 39% of energy from lipids, n-6/n-3 PUFAs ratio: 39) th…

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…

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…

Ocular surface assessment in soft contact lens wearers; the contribution of tear osmolarity among other tests.

: Purpose:  To determine whether tear osmolarity contributes to the assessment of the ocular surface in soft contact lens (CL) wearers. Methods:  Prospective, case–control series in 44 CL wearers (28 tolerant and 16 intolerant) and 34 healthy subjects. Every patient underwent a thorough ophthalmic examination with a tear osmolarity test (TearLab System), 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 did not differ between controls and CL wearers (p = 0.23). Flow cytometry results expressed in antibody-binding capaci…

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…

Actualités en micronutrition. Partie III : nouvelles données sur oméga-3 et angiogenèse

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…

Modulation of autophagy by probiotic bacteria: selecting and engineering strains able to stimulate autophagy in intestinal epithelial cells

National audience

Steady-state levels of retinal 24S-hydroxycholesterol are maintained by glial cells intervention after elevation of intraocular pressure in the rat

Purpose: Our previous studies suggested that CYP46A1 and 24S-hydroxycholesterol. (24SOH) may be associated with glaucoma. Loss of CYP46A1-expressing retinal. ganglion cells is involved in the activation of glia, and therefore possibly in the. disbalance of cholesterol. In this context, the purpose of our present work was to. emphasize the glial and longitudinal CYP46A1 expression after an interventional. glaucoma-related stress triggered by elevated intraocular pressure (IOP). Methods: Sprague–Dawley rats were submitted to laser photocoagulation of the. trabecular meshwork, limbus and episcleral veins in one eye to induce elevated IOP. Rats were euthanized at days 3, 14, 30 and 60 (n = 10 p…

Vitamine D et DMLA : Quels mécanismes ?

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 …

The mechanisms of the action of omega-3s in the retina

Age-related Macular Degeneration (AMD) is the leading cause of visual loss in Western countries after the age of 50y. Based on large-scale epidemiologic studies, it appears now as evident that omega-3 polyunsaturated fatty acids (PUFAs) provide benefits in preventing both, early and late stages of AMD. The aim of this paper is to summarize the knowledge about the biological mechanisms by which omega-3 PUFAs may be protective for the retina. The content of this presentation will range from biochemical data about the occurrence of omega-3 PUFAs in retinal cell membranes to results from cellular and animal studies showing that omega-3 PUFAs can influence processes involved in signal transducti…

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

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

Modification of the monoaminergic neurotransmitters in frontal cortex and hippocampus by dietary trans alpha linolenic acid in piglets

International audience; The effect of partial isomerization of dietary α-linolenic acid on the monoaminergic neurotransmitters in piglets was studied. After feeding the animals for 14 days with diets containing or not trans α-linolenic acid, neurotransmitters related to the monoaminergic function were quantified in the frontal cortex and in the hippocampus. The partial isomerization of dietary α-linolenic acid resulted in increasing endogenous monoamine levels in the frontal cortex (+55% for dopamine) and was related to a very low incorporation of trans polyunsaturated fatty acids. However, feeding animals with a diet in which the imbalance generated by the isomerization of α-linolenic acid…

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

Loss of rod sensitivity and gene expression changes in the retina of fructose-fed insulin-resistant mice

Purpose: Metabolic syndrome is of major concern in Western countries since it predisposes individuals to the development of diabetes. Insulin resistance is one of the biochemical features of the metabolic syndrome. Fructose feeding has been used to elicit insulin resistance in rodents. Our purpose was to characterize the functional and gene expression changes in the retina after long term feeding mice with a fructose-enriched diet.Methods: Control and ApoB100,LDLR-/- mice, a murine model of aging of the human retina, were fed with a 60%-rich fructose diet for 8 months. Scotopic single flash and Flicker electroretinograms were recorded to monitor the response of the retina to flash stimuli. …

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)