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A\u03b2 induces inflammatory responses in RPE cells and recent studies demonstrate the N6\u2010methyladenosine (m6A) regulatory role in RPE cell inflammation. m6A is a reversible epigenetic posttranslational modification, but its relationship with A\u03b2\u2010induced RPE degeneration is yet to be thoroughly investigated. The present study explored the role and mechanism of m6A in A\u03b2\u2010induced RPE degeneration model. This model was induced via intravitreally injecting oligomeric A\u03b2 and the morphology of its retina was analyzed. One of m6A demethylases, the fat mass and obesity\u2010associated (FTO) gene expression, was assessed. An m6A\u2010messenger RNA (mRNA) epitranscriptomic microarray was employed for further bioinformatic analyses. It was confirmed that A\u03b2 induced FTO upregulation within the RPE. Hypopigmentation alterations and structural disorganization were observed in A\u03b2\u2010treated eyes, and inhibition of FTO exacerbated retinal degeneration and RPE impairment. Moreover, the m6A\u2010mRNA epitranscriptomic microarray suggested that protein kinase A (<jats:italic>PKA<\/jats:italic>) was a target of FTO, and the PKA\/cyclic AMP\u2010responsive element binding (CREB) signaling pathway was involved in A\u03b2\u2010induced RPE degeneration. m6A\u2010RNA binding protein immunoprecipitation confirmed that FTO demethylated <jats:italic>PKA<\/jats:italic> within the RPE cells of A\u03b2\u2010treated eyes. Altered expression of PKA and its downstream targets (CREB and brain\u2010derived neurotrophic factor) was confirmed by quantitative reverse\u2010transcription polymerase chain reaction and Western blot analyses. Hence, this study's findings shed light on FTO\u2010mediated m6A modification in A\u03b2\u2010induced RPE degeneration and indicate potential therapeutic targets for AMD.<\/jats:p>","DOI":"10.1002\/cbin.11959","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T18:05:25Z","timestamp":1668535525000},"page":"584-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Fat mass and obesity\u2010associated protein alleviates A\u03b2<sub>1\u201340<\/sub> induced retinal pigment epithelial cells degeneration via PKA\/CREB signaling pathway"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9332-1852","authenticated-orcid":false,"given":"Yifan","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), National Clinical Research Center for Ophthalmic Diseases, 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