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Research Paper|Volume 2, Issue 12|pp 981—989

CD36 plays an important role in the clearance of oxLDL and associated age-dependent sub-retinal deposits

Emilie Picard1, Marianne Houssier2,3,4, Kim Bujold5, Przemyslaw Sapieha1, William Lubell6, Allison Dorfman7, Julie Racine7, Pierre Hardy1, Maria Febbraio8, Pierre Lachapelle7, Huy Ong5, Florian Sennlaub2,3,4,9, Sylvain Chemtob1
  • 1Departments of Pediatrics, Ophthalmology, and Pharmacology, Research Center, Hospitals Ste. Justine and Maisonneuve-Rosemont, Université de Montréal, Montreal, Quebec, Canada
  • 2Inserm, U872, Paris, F-75006 France
  • 3Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris 6, UMR S 872, Paris, F-75006 France
  • 4Université Paris Descartes, UMR S 872, Paris, F-75006 France
  • 5Faculty of Pharmacy, University de Montreal, Montreal, Quebec, Canada
  • 6Departments of Chemistry, University de Montreal, Montreal, Quebec, Canada
  • 7Departments of Ophthalmology, McGill University, Montreal, Quebec, Canada
  • 8Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 4412, USA
  • 9APHP, Département d'Ophthalmologie Hôtel Dieu, Paris, France

* * Equal contribution

Received: October 20, 2010Accepted: November 7, 2010Published: November 9, 2010
https://doi.org/10.18632/aging.100218

Copyright: © 2010 Picard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Age-related macular degeneration (AMD) represents the major cause of vision loss in industrialized nations. Laminar deposits in Bruch's membrane (BM) are among the first prominent histopathologic features, along with drusen formation, and have been found to contain oxidized lipids. Increases in concentrations of oxidized LDL (oxLDL) in plasma are observed with age and high fat high (HFHC) cholesterol diet. CD36 is the principal receptor implicated in uptake of oxLDL, and is expressed in the retinal pigment epithelium (RPE). We determined if CD36 participates in oxLDL uptake in RPE and correspondingly in clearance of sub-retinal deposits. Uptake of oxLDL by RPE in vitro and in vivo was CD36-dependent. CD36 deficiency in mice resulted in age-associated accumulation of oxLDL and sub-retinal BM thickening, despite fed a regular diet. Conversely, treatment of HFHC-fed ApoE null mice with a CD36 agonist, EP80317 (300 μg/kg/day), markedly diminished thickening of BM, and partially preserved (in part) photoreceptor function. In conclusion, our data uncover a new role for CD36 in the clearance of oxidized lipids from BM and in the prevention of age-dependent sub-retinal laminar deposits.