The CD36 Ligand‐Promoted Autophagy Protects Retinal Pigment Epithelial Cells from Oxidative Stress
Marie‐France Dorion, Mukandila Mulumba, Shuya Kasai, Ken Itoh, William D. Lubell, Huy Ong
Abstract
The retinal pigment epithelium (RPE) performs many functions that maintain photoreceptor health. Oxidative damage to the RPE is a critical component in the pathogenesis of eye diseases such as age‐related macular degeneration (AMD). Ligands of the cluster of differentiation 36 (CD36) have previously preserved photoreceptor integrity in mouse models of AMD. The cytoprotective effect of the CD36 ligand MPE‐001 on RPE cells has now been elucidated employing a model of oxidative stress. Sodium iodate (NaIO 3 ) induced formation of reactive oxygen species and apoptosis in human RPE cells, which were decreased by MPE‐001 without affecting antioxidant enzyme transcription. Immunoblotting and immunostaining assays showed a restorative effect of MPE‐001 on the autophagic flux disrupted by NaIO 3 , which was associated with an increase in syntaxin 17‐positive mature autophagosomes. The cytoprotective effect of MPE‐001 was completely abolished by the autophagy inhibitors wortmannin and bafilomycin A1. In conclusion, we report for the first time an autophagy‐dependent protection of RPE cells from oxidative stress by a CD36 ligand.