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
- 1 Departments of Pediatrics, Ophthalmology, and Pharmacology, Research Center, Hospitals Ste. Justine and Maisonneuve-Rosemont, Université de Montréal, Montreal, Quebec, Canada
- 2 Inserm, U872, Paris, F-75006 France
- 3 Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris 6, UMR S 872, Paris, F-75006 France
- 4 Université Paris Descartes, UMR S 872, Paris, F-75006 France
- 5 Faculty of Pharmacy, University de Montreal, Montreal, Quebec, Canada
- 6 Departments of Chemistry, University de Montreal, Montreal, Quebec, Canada
- 7 Departments of Ophthalmology, McGill University, Montreal, Quebec, Canada
- 8 Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 4412, USA
- 9 APHP, Département d'Ophthalmologie Hôtel Dieu, Paris, France
Received: October 20, 2010 Accepted: November 7, 2010 Published: November 9, 2010
https://doi.org/10.18632/aging.100218How to Cite
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.