title: CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.
abstract: BACKGROUND
  In the Western world, a major cause of blindness is age-related macular degeneration (AMD). Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD.
  
  
  RESULTS
  We here show that deficiency of CD36, which participates in outer segment (OS) phagocytosis by the retinal pigment epithelium (RPE) in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR) and CD36-/- mice). Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF) expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency.
  
  
  CONCLUSIONS
  CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U872, Paris, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Houssier
authors.forename: William
authors.initials: W
authors.lastname: Raoul
authors.forename: Sophie
authors.initials: S
authors.lastname: Lavalette
authors.forename: Nicole
authors.initials: N
authors.lastname: Keller
authors.forename: Xavier
authors.initials: X
authors.lastname: Guillonneau
authors.forename: Barbara
authors.initials: B
authors.lastname: Baragatti
authors.forename: Laurent
authors.initials: L
authors.lastname: Jonet
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Jeanny
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.forename: Flavio
authors.initials: F
authors.lastname: Coceani
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Pierre
authors.initials: P
authors.lastname: Lachapelle
authors.forename: Huy
authors.initials: H
authors.lastname: Ong
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D015862:Choroid Diseases / Q000201:enzymology* / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012162:Retinal Degeneration / Q000201:enzymology / Q000235:genetics
chemical_list: D018955:CD36 Antigens; D051546:Cyclooxygenase 2