摘要
Subretinal inflammation plays a critical role in retinal degenerative diseases.Although activated macrophages have been shown to play a key role in the progression of retinopathies and specifically in age-related macular degeneration,little is known about the mechanisms involved in the loss of photoreceptors leading to vision impairment.In our study on retinal damages induced by photo-oxidative stress,we have observed that CD36-deficient mice featured less subretinal macrophage accumulation with attenuated photoreceptor degeneration compared to wild-type(WT)mice.Treatment with CD36-selective azapeptide ligand(labelled MPE-001)as modulator of the inflammatory environment of the retina reduced subretinal macrophage/activated microglia accumulation with preservation of photoreceptor layers and function assessed by ERG in WT,in a CD36-dependent manner.The azapeptide modulated the transcriptome of subretinal macrophage/activated microglia by reducing pro-inflammatory markers.In isolated macrophages,the CD36-selective azapeptide induced dissociation of the CD36-TLR2/6 heterodimer complex(using FRET)altering the TLR2 signaling pathway,thus decreasing NF-κB activation and inflammasome activity.The azapeptide also incurred cytoprotection against photoreceptor apoptosis elicited by activated macrophages.These findings suggest that the azapeptide as ligand of co-receptor CD36 decreases the inflammatory response by modulating CD36-TLR2/6 complex signaling pathway in macrophages,and suggests its potential application in the treatment of retinal degenerative diseases.
