Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland
Katrin Klee
Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
Vyara Todorova
Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland; Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland
Regula Steiner
Institute of Clinical Chemistry, University of Zurich, Schlieren, Switzerland
Alaa Othman
Institute of Clinical Chemistry, University of Zurich, Schlieren, Switzerland
Saskia van der Velde-Visser
Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
Marijana Samardzija
Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland
Isabelle Meneau
Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland
Maya Barben
Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland
Duygu Karademir
Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
Valda Pauzuolyte
Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland
Department of Ophthalmology, University of Florida, Gainesville, United States
Frank Blaser
Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland
Christoph Ullmer
Roche Pharma Research and Early Development, Roche Innovation Center Basel, F Hoffmann-La Roche Ltd., Basel, Switzerland
Joshua L Dunaief
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, United States
Thorsten Hornemann
Institute of Clinical Chemistry, University of Zurich, Schlieren, Switzerland
Lucia Rohrer
Institute of Clinical Chemistry, University of Zurich, Schlieren, Switzerland
Anneke den Hollander
Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands; Department of Ophthalmology, Radboud University Medical Center, Nijmegen, Netherlands
Arnold von Eckardstein
Institute of Clinical Chemistry, University of Zurich, Schlieren, Switzerland
Jürgen Fingerle
Natural and Medical Sciences Institute, University of Tübingen, Tübingen, Germany
Cyrille Maugeais
Roche Pharma Research and Early Development, Roche Innovation Center Basel, F Hoffmann-La Roche Ltd., Basel, Switzerland
Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Schlieren, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland
Age-related macular degeneration (AMD) is a progressive disease of the retinal pigment epithelium (RPE) and the retina leading to loss of central vision. Polymorphisms in genes involved in lipid metabolism, including the ATP-binding cassette transporter A1 (ABCA1), have been associated with AMD risk. However, the significance of retinal lipid handling for AMD pathogenesis remains elusive. Here, we study the contribution of lipid efflux in the RPE by generating a mouse model lacking ABCA1 and its partner ABCG1 specifically in this layer. Mutant mice show lipid accumulation in the RPE, reduced RPE and retinal function, retinal inflammation and RPE/photoreceptor degeneration. Data from human cell lines indicate that the ABCA1 AMD risk-conferring allele decreases ABCA1 expression, identifying the potential molecular cause that underlies the genetic risk for AMD. Our results highlight the essential homeostatic role for lipid efflux in the RPE and suggest a pathogenic contribution of reduced ABCA1 function to AMD.
