Cd36 Is Involved In Sub-retinal Deposits In Age-related Retinal Degeneration

Abstract

Purpose: : The first prominent histopathologic features of age-related macular degeneration, are laminar deposits in Bruch’s membrane (BM), along with drusen formation, that contain oxidized lipids. Increases in concentrations of oxidized LDL (oxLDL) in plasma are observed with age and high fat high cholesterol diet. CD36 is the principal lipid scavenger receptor implicated in uptake of oxLDL and is expressed in the retinal pigment epithelium (RPE). We have previously reported that a deficiency in CD36 leads to retinal degeneration and choroidal involution (Houssier et al. Plos Med, 2008).

Methods: : We used aged CD36-/- mice, and ApoE-/- mice known to exhibit subretinal deposits, to determined effect of CD36 deficiency in oxLDL uptake by RPE, in BM thickening determined by electron microscopy and on photoreceptors activities evaluated by electroretinography.

Results: : We determined that CD36 is essential in oxLDL uptake in RPE and correspondingly in clearance of sub-retinal deposits. In aged CD36 and to a greater extent in CD36/ApoE null mice (compared to wild type animals), subretinal deposits and BM thickening were observed. Treatment of ApoE-/- mice with a CD36 positive modulator, EP80317 (300 ug/kg/day) for 12 weeks attenuated the accumulation in sub-retinal debris and preserved in part photoreceptor function.

Conclusions: : In conclusion, we hereby demonstrate an important role for CD36 in the clearance of oxidized lipids by RPE and in the prevention of age-dependent sub-retinal laminar deposits.

Keywords: age-related macular degeneration • Bruch's membrane • lipids