Jadwiga Oczos1, Iryna Sutter2, Barbara Kloeckener-Gruissem3, Wolfgang Berger4, Meliana Riwanto5, Katharina Rentsch2, Thorsten Hornemann2, Arnold von Eckardstein2, Christian Grimm6. 1. Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Zurich, Switzerland. 2. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland Institute of Clinical Chemistry, University of Zurich, Zurich, Switzerland. 3. Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland Department of Biology, ETH Zurich, Zurich, Switzerland. 4. 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. 5. Institute of Physiology, University of Zurich, Zurich, Switzerland. 6. 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.
Abstract
PURPOSE: 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. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: 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. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Maya Barben; Divya Ail; Federica Storti; Katrin Klee; Christian Schori; Marijana Samardzija; Stylianos Michalakis; Martin Biel; Isabelle Meneau; Frank Blaser; Daniel Barthelmes; Christian Grimm Journal: Cell Death Differ Date: 2018-04-17 Impact factor: 15.828
Authors: Federica Storti; Katrin Klee; Vyara Todorova; Regula Steiner; Alaa Othman; Saskia van der Velde-Visser; Marijana Samardzija; Isabelle Meneau; Maya Barben; Duygu Karademir; Valda Pauzuolyte; Sanford L Boye; Frank Blaser; Christoph Ullmer; Joshua L Dunaief; Thorsten Hornemann; Lucia Rohrer; Anneke den Hollander; Arnold von Eckardstein; Jürgen Fingerle; Cyrille Maugeais; Christian Grimm Journal: Elife Date: 2019-03-13 Impact factor: 8.140