Immunometabolic modulation of retinal inflammation by CD36 ligand

摘要: In subretinal inflammation, activated mononuclear phagocytes (MP) play a key role in the progression of retinopathies. Little is known about mechanism involved loss photoreceptors leading to vision impairment. Studying retinal damage induced by photo-oxidative stress, we observed that cluster differentiation 36 (CD36)-deficient mice featured less MP accumulation and attenuated photoreceptor degeneration. Moreover, treatment with CD36-selective azapeptide ligand (MPE-001) reduced wild type preserved layers function as assessed electroretinography CD36-dependent manner. The modulated transcriptome reducing pro-inflammatory markers. isolated MP, MPE-001 dissociation CD36-Toll-like receptor 2 (TLR2) oligomeric complex, decreasing nuclear factor-kappa B (NF-κB) NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. addition, caused an aerobic metabolic shift involving peroxisome proliferator-activated receptor-γ (PPAR-γ) activation, which turn mitigated inflammation. Accordingly, PPAR-γ inhibition blocked cytoprotective effect on apoptosis elicited MP. By altering metabolism, decreased immune responses alleviate subsequent inflammation-dependent neuronal injury characteristic various vision-threatening disorders.