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Group : Eye, Nutrition and Cell Signalling Research Group, Centre for Taste and Feeding Behaviour, AgroSup Dijon, CNRS, INRA, University of Burgundy, Dijon, France

Key members: Ségolène Gambert, Elodie Masson, Lionel Bretillon, Niyazi Acar, Lucy Martine

Contact: lionel.bretillon@inra.fr

Research activities: 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.

In connection with ENOR activities, our objective is to decipher and better understand how cholesterol homeostasis participate in the functionning of the retina, and whether it is implicated in its age-associated disorders. 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.

 

Key papers related to ENOR

Gambert, S., P.-H. Gabrielle, E. Masson, E. Leger-Charnay, A. Ferrerro, A. Vannier, C. Gendrault, M. Lachot, C. Creuzot-Garcher, A. Bron, S. Gregoire, L. Leclere, L. Martine, G. Lucchi, C. Truntzer, D. Pecqueur, and L. Bretillon. 2017. Cholesterol metabolism and glaucoma: Modulation of Muller cell membrane organization by 24S-hydroxycholesterol. Chemistry and Physics of Lipids. 207:179-191.

Filomenko, R., C. Fourgeux, L. Bretillon, and S. Gambert-Nicot. 2015. Oxysterols: Influence on plasma membrane rafts microdomains and development of ocular diseases. Steroids. 99:259–265.

Fourgeux, C., L. Martine, N. Acar, A.M. Bron, C.P. Creuzot-Garcher, and L. Bretillon. 2014. In vivo consequences of cholesterol-24S-hydroxylase (CYP46A1) inhibition by voriconazole on cholesterol homeostasis and function in the rat retina. Biochemical and Biophysical Research Communications. 446:775-781.

Fourgeux, C., B. Dugas, F. Richard, I. Bjorkhem, N. Acar, A.M. Bron, J.-F. Korobelnik, N. Leveziel, J. Zerbib, N. Puche, C.P. Creuzot-Garcher, E. Souied, and L. Bretillon. 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. Investigative Ophthalmology & Visual Science. 53:7026-7033.

Fourgeux, C., L. Martine, B. Pasquis, M.-A. Maire, N. Acar, C. Creuzot-Garcher, A. Bron, and L. Bretillon. 2012. Steady-state levels of retinal 24S-hydroxycholesterol are maintained by glial cells intervention after elevation of intraocular pressure in the rat. Acta Ophthalmologica. 90:e560-e567.

Fourgeux, C., A. Bron, N. Acar, C. Creuzot-Garcher, and L. Bretillon. 2011. 24S-hydroxycholesterol and cholesterol-24S-hydroxylase (CYP46A1) in the retina: from cholesterol homeostasis to pathophysiology of glaucoma. Chemistry and Physics of Lipids. 164:496-499.

Fourgeux, C., L. Martine, I. Bjorkhem, U. Diczfalusy, C. Joffre, N. Acar, C. Creuzot-Garcher, A. Bron, and L. Bretillon. 2009. Primary Open-Angle Glaucoma: Association with Cholesterol 24S-Hydroxylase (CYP46A1) Gene Polymorphism and Plasma 24-Hydroxycholesterol Levels. Investigative Ophthalmology & Visual Science. 50:5712-5717.

Bretillon, L., U. Diczfalusy, I. Bjorkhem, M.-A. Maire, L. Martine, C. Joffre, and N. Acar. 2007. Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in neurons of the neural retina. Current Eye Research. 32:361-366.