title: CD36 plays an important role in the clearance of oxLDL and associated age-dependent sub-retinal deposits.
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 RPEin 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.
authors.affiliation: Department of Pediatrics, Hospitals Ste. Justine and Maisonneuve-Rosemont, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Emilie
authors.initials: E
authors.lastname: Picard
authors.forename: Marianne
authors.initials: M
authors.lastname: Houssier
authors.forename: Kim
authors.initials: K
authors.lastname: Bujold
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sapieha
authors.forename: William
authors.initials: W
authors.lastname: Lubell
authors.forename: Allison
authors.initials: A
authors.lastname: Dorfman
authors.forename: Julie
authors.initials: J
authors.lastname: Racine
authors.forename: Pierre
authors.initials: P
authors.lastname: Hardy
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
authors.forename: Pierre
authors.initials: P
authors.lastname: Lachapelle
authors.forename: Huy
authors.initials: H
authors.lastname: Ong
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D016570:Bruch Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004041:Dietary Fats / Q000378:metabolism; D004195:Disease Models, Animal; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D004041:Dietary Fats; C468852:EP80317; D008077:Lipoproteins, LDL; D009842:Oligopeptides; C099252:oxidized low density lipoprotein