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Eye, nutrition and cell signalling


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Researchers

L. Bretillon, M-A. Bringer, A. Bron, S. Gambert Nicot, E. Masson.

Enginneers and technicians

B. Buteau, S. Grégoire, L. Leclere, M-A. Maire, L. Martine.

PhD students

L. Arnould, J-B. Bizeau, P. Gabrielle, R. Karadayi, G. Vasku.

Lipids display a large variety of functions in the retina: structure, functionality, pathophysiological associations, therapeutic value. In order to improve scientific knowledge and identify novel applications in the relationships between diet and retinal pathophysiology, the Eye, Nutrition and Cell Signalling Research Group aims at studying the roles of lipids in the physiology and dysfunctions of the retina in relation to retinopathies. One if not the main strength of our group stands in its translational research approach that is led at experimental level and in human studies. Since the group gathers clinicians and researchers, the projects timely benefits from both fundamental science and clinical concerns.

Key words : Retina, lipid, diet, ageing, membrane dynamics, angiogenesis, neurodegeneration, autophagy.

Thematic : Lipids and retina
Our projects aim at better understanding how lipid and lipid metabolism intervene in the functioning and dysfunctions of the retina.

Research group in detail Open all the tabs

Our objective is to decipher and better understand how lipids and lipid metabolism participate in the functionning of the retina, and whether their are implicated in its age-associated disorders.

Theme 1 : Roles of lipids in the functions and dysfunctions in the retina

    Lipids represent a large variety of molecules with various properties. Amon them, the Eye, Nutrition and Signalling research group focuses on the role of plasmalogens, cholesterol and gangliosides in the retina, in relation to aging processes and dysfunctions.
    The projects are channelled in two axes:
  • - Lipids and cell interactions
    The objective is to better understand the role of cell dynamics and cell signalling in the death and survival of retinal ganglion cells. We aim at deciphering the mechanisms that surround the interactions between retinal ganglion cells, which death is responsible for visual field loss in glaucoma, and glial cells in the retina. A peculiar attention is paid on the importance of gangliosides and 24S-hydroxycholesterol, a metabolite of cholesterol formed by cholesterol-24S-hydroxylase, in the response of glial cells to retinal ganglion cell death, with special emphasis on ganglioside-rich lipid rafts as cell signalling platforms.
  • - Lipids and vascular development
    Plasmalogens account for an important part of phospholipids in the retina, an as such are considered as reservoirs of polyunsaturated fatty acids. The objective is to better understand the role of plasmalogens in the metabolism of glial cells (astrocytes, Müller cells) and the interactions during vascular development.

Theme 2 : Diet and retina

  • - Lipid intakes, structure and functionning of the retina during the lifespan
    Diet is one of the environmental factors that participate in the functionning and aging of the retina. The objective is to characterize the importance of dietary factors (macro- and micronutrient intakes) in the risk of retinal pathologies (Age-related Macular Degeneration, Diabetic Retinopathy, Glaucomas) in clinical studies.
  • - Dietary disbalances, autophagy and pathophysiology
    The objective is to elucidate how the retina adapts to disbalanced dietary intakes, and define the long-term consequences. The role of autophagy as an adaptive mechanism and the long term consequences in neovascular complications are especially studied.

Analytical chemistry

Lipid analysis using thin layer, gas or liquid chromatography coupled with FID (total lipids, fatty acids and sterols), UV (carotenoïds), Corona (phospholipids), mass spectrometer (oxysterols, phospholipids, plasmalogens and gangliosides).

Physiology

in vivo exploration of retina structure and function using angiography and electroretinography.

Others

preparation of lipid rafts

Human model

- Healthy subjects and patients (plasma, red blood cells)
- Deceased donors (retina and other ocular structures, plasma, red blood cells)

Rodent

- Rats and mice
- Induced models of retinal diseases : glaucoma (accute hypertonia induced by ischemia-reperfusion and chronic hypertonia induced by laser photocoagulation), age-related macular degeneration (choroïdal neovascularisation induced by laser impacts).
-  Genetic models : ApoB100,LDLR-/- ; DHAPAT-/- ; GM2 synthase -/- et GD3 synthase -/- mice.

In vitro

- Cultures primaires humaine et murine (astrocytes, cellules de Müller, cellules de l’épithélium pigmentaire rétinien, cellules endothéliales, monocytes)
- Lignées (ARPE-19, HUVEC, C13NJ, THP-1, HeLa-LC3GFP)

ANR BLISAR : Biomarkers of lipid status and metabolism during retinal aging

LabEx LipSTIC : Lipoproteins and health : prevention and treatment of non vascular inflammatory diseases and cancer

Masson E, Sibille E, Martine L, Chaux-Picquet F, Bretillon L and Berdeaux O (2015). Apprehending ganglioside diversity: a comprehensive methodological approach. J Lipid Res 56 (9): 1821-1835.

Thierry M, Pasquis B, Buteau B, Fourgeux C, Dembele D, Leclere L, Gambert-Nicot S, Acar N, Bron AM, Creuzot-Garcher CP and Bretillon L (2015). Early adaptive response of the retina to a pro-diabetogenic diet: Impairment of cone response and gene expression changes in high-fructose fed rats. Exp Eye Res 135: 37-46.

Saab S, Buteau B, Leclère L, Bron A, Creuzot-Garcher C, Bretillon L and Acar N (2014). Involvement of plasmalogens in post-natal retinal vascular development. PLoS ONE 9 (6): e101076.

Thierry M, Pasquis B, Acar N, Grégoire S, Febvret V, Buteau B, Gambert-Nicot S, Bron A, Creuzot-Garcher C and Bretillon L (2014). Metabolic syndrome triggered by high-fructose diet favors choroidal neovascularization and impairs retinal light sensitivity in the rat. PLoS ONE 9 (11): e112450.

Fares-Taie L, Gerber S, Chassaing N, Clayton-Smith J, Hanein S, Silva E, Serey M, Serre V, Gérard X, Baumann C, Plessis G, Demeer B, Brétillon L, Bole C, Nitschke P, Munnich A, Lyonnet S, Calvas P, Kaplan J, Ragge N and Rozet J-M (2013). ALDH1A3 Mutations Cause Recessive Anophthalmia and Microphthalmia. Am J Hum Genet 92 (2): 265-270.

Acar N, Berdeaux O, Gregoire S, Cabaret S, Martine L, Gain P, Thuret G, Creuzot-Garcher C, Bron A and Bretillon L (2012). Lipid Composition of the Human Eye: Are Red Blood Cells a Good Mirror of Retinal and Optic Nerve Fatty Acids? PLoS ONE 7 (4): e35102.

Fourgeux C, Dugas B, Richard F, Björkhem I, Acar N, Bron AM, Korobelnik J-F, Leveziel N, Zerbib J, Puche N, Creuzot-Garcher CP, Souied E and Bretillon L (2012). Single Nucleotide Polymorphism in the Cholesterol-24S-Hydroxylase (CYP46A1) Gene and Its Association with CFH and LOC387715 Gene Polymorphisms in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 53 (11): 7026-7033.

Lafourcade M, Duffaud A, Mato S, Sepers M, Matias I, De Smedt V, Labrousse V, Bretillon L, Matute C, Rodríguez-Puertas R, Layé S and Manzoni O (2011). Nutritional Omega-3 deficiency abolishes endocannabinoid mediated neuronal functions. Nature Neurosci 14 (3): 345-350.

Simon E, Bardet B, Gregoire S, Acar N, Bron AM, Creuzot-Garcher CP and Bretillon L (2011). Decreasing dietary linoleic acid promotes long chain omega-3 fatty acid incorporation into rat retina and modifies gene expression. Exp Eye Res 93 (11): 628-635.

Fliesler SJ and Bretillon L (2010). The ins and outs of cholesterol in the vertebrate retina. J Lipid Res 51 (12): 3399-3413.

  • ANR
  • Bourgogne
  • FEDER