title: Lack of paraoxonase 1 alters phospholipid composition, but not morphology and function of the mouse retina.
abstract: OBJECTIVE
  Biochemical and genetic analyses established a contribution of lipid metabolism to AMD pathology. Paraoxonase 1 (PON1) is an antioxidative protein involved in high density lipoprotein (HDL) function and was found to be associated with AMD. Here, we used Pon1(-/-) mice to study the influence of PON1 on retinal physiology and to reveal the potential impact of PON1 on AMD etiology.
  
  
  METHODS
  Laser capture microdissection served to isolate single retinal layers. Retinal function was assessed by ERG. Retinal and RPE morphology were monitored by fundus imaging, fluorescein angiography, light and transmission electron microscopy, and immunofluorescence microscopy. Levels of mRNA and composition of phospholipid species were determined by real-time PCR and LC-MS, respectively.
  
  
  RESULTS
  Adult (8 weeks old) Pon1(-/-) mice displayed normal retinal function and morphology, but their retinas contained reduced amounts of lysophosphatidylcholines (LPCs) compared to controls. Aged (12 months old) Pon1(-/-) animals did not show any morphologic or molecular signs of photoreceptor or RPE degeneration, or of accelerated aging. Photoreceptors of Pon1(-/-) and control mice were similarly susceptible to light damage.
  
  
  CONCLUSIONS
  Results indicated that PON1 is not essential for normal development, function, ageing, and the defense against light damage of the mouse retina. Reduced levels of LPCs in eyes of Pon1(-/-) mice may reflect a decreased activity of phospholipase A2 or altered antioxidative activity in aged eyes.
authors.affiliation: Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Zurich, Switzerland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Oczos
authors.affiliation: Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland Institute of Clinical Chemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Iryna
authors.initials: I
authors.lastname: Sutter
authors.affiliation: Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kloeckener-Gruissem
authors.affiliation: Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland Zurich Center of Neuroscience (ZNZ), Zurich, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Berger
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Meliana
authors.initials: M
authors.lastname: Riwanto
authors.affiliation: Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland Institute of Clinical Chemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Rentsch
authors.affiliation: Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland Institute of Clinical Chemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hornemann
authors.affiliation: Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland Institute of Clinical Chemistry, University of Zurich, Zurich, Switzerland.
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.affiliation: Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Zurich, Switzerland Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland Zurich Center of Neuroscience (ZNZ), Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D043303:Aryldialkylphosphatase / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D004596:Electroretinography; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005786:Gene Expression Regulation; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010743:Phospholipids / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D010743:Phospholipids; D012333:RNA, Messenger; D043303:Aryldialkylphosphatase
keywords: age-related macular degeneration; paraoxonase 1; phospholipids; retina