0000000001173065
AUTHOR
Laurent Leclere
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
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…
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…
Incorporation and metabolism of dietary trans isomers of linolenic acid alter the fatty acid profile of rat tissues
To study the influence on lipid metabolism and platelet aggregation of the fatty acid isomerization that occurs during heat treatment, weanling rats were fed for 8 wk a diet enriched with 5% isomerized (experimental group) or normal (control group) canola oil. Geometrical isomers of alpha-linolenic acid representing 0.2 g/100 g of the experimental diet were incorporated into liver, platelets, aorta and heart, at the expense of their cis homologue and of 18:2(n-6). The major isomer, 9c,12c,15t-18:3, was also metabolized to 5c,8c,11c,14c,17t-20:5 and to an unknown compound, found in liver, platelets and aorta, which has been identified tentatively as 7c, 10c,13c,16c,19t-22:5. The greater 20:4…
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…
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 …
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 …
Incorporation and metabolism of trans 20∶5 in endothelial cells. Effect on prostacyclin synthesis
To study the ability of long-chain trans fatty acids (FA) to be incorporated and metabolized into endothelial cells, bovine aortic endothelial cells were incubated with medium enriched eicosapentaenoic acid (EPA) bound to albumin (M2) or one of its geometrical isomers: 20:5 5c,8c,11t,14c,17c (M3), 20:5 5c,8c,11c,14c,17t (M4), or 20:5 5c,8c,11t,14c,17t (M5). After 48 h of incubation, supernatant and cells were harvested and their lipids were analyzed, including prostacyclin synthesis. EPA and 22:5n-3 of endothelial cells incubated with M2 were, respectively, three and two times higher than in control cells (incubated in M1, without any fatty acid added), whereas 22:6n-3 increased only in the…
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…
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…
Proteomic analysis of sub-retinal deposits in age-related macular degeneration
National audience
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.
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
Cholesterol homeostasis and retinal stress in anterior ischemic optic neuropathy
International audience
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…
Gap junction intercellular communication (GJIC) is regulated by plasmalogens in retinal macroglial cells
International audience