| First Author | Mellal K | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 12903 |
| PubMed ID | 31501473 | Mgi Jnum | J:284026 |
| Mgi Id | MGI:6389331 | Doi | 10.1038/s41598-019-49472-8 |
| Citation | Mellal K, et al. (2019) Immunometabolic modulation of retinal inflammation by CD36 ligand. Sci Rep 9(1):12903 |
| abstractText | In subretinal inflammation, activated mononuclear phagocytes (MP) play a key role in the progression of retinopathies. Little is known about the mechanism involved in the loss of photoreceptors leading to vision impairment. Studying retinal damage induced by photo-oxidative stress, we observed that cluster of differentiation 36 (CD36)-deficient mice featured less subretinal MP accumulation and attenuated photoreceptor degeneration. Moreover, treatment with a CD36-selective azapeptide ligand (MPE-001) reduced subretinal activated MP accumulation in wild type mice and preserved photoreceptor layers and function as assessed by electroretinography in a CD36-dependent manner. The azapeptide modulated the transcriptome of subretinal activated MP by reducing pro-inflammatory markers. In isolated MP, MPE-001 induced dissociation of the CD36-Toll-like receptor 2 (TLR2) oligomeric complex, decreasing nuclear factor-kappa B (NF-kappaB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. In addition, MPE-001 caused an aerobic metabolic shift in activated MP, involving peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation, which in turn mitigated inflammation. Accordingly, PPAR-gamma inhibition blocked the cytoprotective effect of MPE-001 on photoreceptor apoptosis elicited by activated MP. By altering activated MP metabolism, MPE-001 decreased immune responses to alleviate subsequent inflammation-dependent neuronal injury characteristic of various vision-threatening retinal disorders. |
