CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

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Version: Final published version
Serval ID
serval:BIB_48D756028659
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.
Journal
Plos Medicine
Author(s)
Houssier M., Raoul W., Lavalette S., Keller N., Guillonneau X., Baragatti B., Jonet L., Jeanny J.C., Behar-Cohen F., Coceani F., Scherman D., Lachapelle P., Ong H., Chemtob S., Sennlaub F.
ISSN
1549-1676 (Electronic)
ISSN-L
1549-1277
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
5
Number
2
Pages
e39
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
METHODS AND FINDINGS: 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.
Keywords
Animals, Antigens, CD36/genetics, Antigens, CD36/physiology, Cells, Cultured, Choroid Diseases/enzymology, Choroid Diseases/genetics, Cyclooxygenase 2/genetics, Cyclooxygenase 2/metabolism, Down-Regulation/genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Rats, Rats, Inbred SHR, Rats, Wistar, Retinal Degeneration/enzymology, Retinal Degeneration/genetics
Pubmed
Web of science
Open Access
Yes
Create date
27/08/2013 10:17
Last modification date
20/08/2019 13:55
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