title: Defective ceramide synthases in mice cause reduced amplitudes in electroretinograms and altered sphingolipid composition in retina and cornea.
abstract: Complex sphingolipids are strongly expressed in neuronal tissue and contain ceramides in their backbone. Ceramides are synthesized by six ceramide synthases (CerS1-6). Although it is known that each tissue has a unique profile of ceramide synthase expression and ceramide synthases are implicated in several neurodegenerative disorders, the expression of ceramide synthase isoforms has not been investigated in the retina. Here we demonstrate CerS1, CerS2 and CerS4 expression in mouse retina and cornea, with CerS4 ubiquitously expressed in all retinal neurons and Müller cells. To test whether ceramide synthase deficiency affects retinal function, we compared electroretinograms and retina morphology between wild-type and CerS1-, CerS2- and CerS4-deficient mice. Electroretinograms were strongly reduced in amplitude in ceramide synthase-deficient mice, suggesting that signalling in the outer retina is affected. However, the number of photoreceptors and cone outer segment length were unaltered and no changes in retinal layer thickness or synaptic structures were found. Mass spectrometric analyses of ceramides, hexosyl-ceramides and sphingomyelins showed that C20 to C24 acyl-containing species were decreased whereas C16-containing species were increased in the retina of ceramide synthase-deficient mice. Similar but smaller changes were also found in the cornea. Thus, we hypothesize that the replacement of very long-chain fatty acyl residues by shorter C16 residues may affect the electrical properties of retina and cornea, and alter receptor-mediated signal transduction, vesicle-mediated synaptic transmission or corneal light transmission. Future studies need to identify the molecular targets of ceramides or derived sphingolipids in light signal transduction and transmission in the eye.
authors.affiliation: Neurobiology, University of Oldenburg, 26111, Oldenburg, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Brüggen
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kremser
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bickert
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ebel
authors.affiliation: Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, Bonn, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Vom Dorp
authors.affiliation: Neurobiology, University of Oldenburg, 26111, Oldenburg, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Schultz
authors.affiliation: Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dörmann
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.affiliation: Neurobiology, University of Oldenburg, 26111, Oldenburg, Germany.|Research Center Neurosensory Science, University of Oldenburg, Oldenburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Dedek
mesh_terms: D000818:Animals; D002518:Ceramides / Q000378:metabolism; D003315:Cornea / Q000201:enzymology / Q000378:metabolism*; D004596:Electroretinography; D055537:Light Signal Transduction; D051379:Mice; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D002518:Ceramides; D013107:Sphingolipids; D010088:Oxidoreductases; C108138:dihydroceramide desaturase
keywords: cell membrane; cornea; electroretinogram; photoreceptor; retinal circuitry; sphingolipids