Fat mass and obesity‐associated protein alleviates Aβ1–40 induced retinal pigment epithelial cells degeneration via PKA/CREB signaling pathway

• DOI: 10.1002/cbin.11959
• Publication Date: 2022-11-15T18:05:25Z
• Authors: Yifan Hu; Jieqiong Chen; Yuwei Wang; Junran Sun; Peirong Huang; Jingyang Feng; Te Liu; Xiaodong Sun
• Keywords: N6-Methyladenosine

Abstract Amyloid‐β (Aβ) is thought to be a critical pathologic factor of retinal pigment epithelium (RPE) degeneration in age‐related macular (AMD). Aβ induces inflammatory responses RPE cells and recent studies demonstrate the N6‐methyladenosine (m6A) regulatory role cell inflammation. m6A reversible epigenetic posttranslational modification, but its relationship with Aβ‐induced yet thoroughly investigated. The present study explored mechanism model. This model was induced via intravitreally injecting oligomeric morphology retina analyzed. One demethylases, fat mass obesity‐associated (FTO) gene expression, assessed. An m6A‐messenger RNA (mRNA) epitranscriptomic microarray employed for further bioinformatic analyses. It confirmed that FTO upregulation within RPE. Hypopigmentation alterations structural disorganization were observed Aβ‐treated eyes, inhibition exacerbated impairment. Moreover, m6A‐mRNA suggested protein kinase A ( PKA ) target FTO, PKA/cyclic AMP‐responsive element binding (CREB) signaling pathway involved degeneration. m6A‐RNA immunoprecipitation demethylated eyes. Altered expression downstream targets (CREB brain‐derived neurotrophic factor) by quantitative reverse‐transcription polymerase chain reaction Western blot Hence, this study's findings shed light on FTO‐mediated modification indicate potential therapeutic AMD.