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 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)

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…

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…

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…

Impact of dietary fatty acids on autophagy in the retina

Cholesterol metabolism, autophagy and aging

National audience

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…

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 …

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…

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…

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…

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

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

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

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…

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…

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