{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:47:35Z","timestamp":1774421255065,"version":"3.50.1"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00333553"],"award-info":[{"award-number":["RS-2024-00333553"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2022-NR067329"],"award-info":[{"award-number":["RS-2022-NR067329"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-02213506"],"award-info":[{"award-number":["RS-2025-02213506"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Age-related macular degeneration (AMD) represents a multifactorial disease that is influenced by age, genetic, and environmental factors. AMD is characterized by dysfunction of the retinal pigment epithelium (RPE) resulting from oxidative stress, inflammation, and complement activation. As the disease progresses, the loss of the RPE and photoreceptors leads to geographic atrophy, which is a hallmark of dry AMD. Although research is ongoing, there is currently no established effective treatment for dry AMD. Notably, circular RNAs (circRNAs) have been studied in various diseases; however, the role of circRNAs in eye diseases remains poorly understood. To fill this gap, this study aimed to investigate circRNAs as potential therapeutic targets for dry AMD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified candidate circRNAs using a laser-induced choroidal neovascularization (CNV) model. The function of circAFF3 was investigated through knockdown experiments in ARPE-19 cells, followed by transcriptomic analysis, pathway enrichment, and functional assays, including qPCR, western blotting, immunofluorescence, monocyte adhesion, and measurements of ROS, iron, lipid peroxidation, and apoptosis. Interaction between circAFF3 and p53 was explored using binding prediction, RNA-binding protein immunoprecipitation, and cycloheximide chase assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that circAff3 levels were downregulated in RPE samples at day 3 after laser injury. Moreover, silencing circAFF3 induced an inflammatory response in ARPE-19 cells. Based on these results, a subsequent transcriptomic analysis of circAFF3 knockdown in ARPE-19 cells was conducted to further elucidate its function. These analyses showed that genes downregulated by circAFF3 knockdown in ARPE-19 cells were significantly associated with retinal degeneration. Additionally, reduced circAFF3 expression promoted a decrease in ID2 levels, resulting in increased oxidative stress and cell death. Our study further demonstrated that circAFF3 directly interacts with p53, thereby regulating ID2 expression in ARPE-19 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, our study reveals that circAFF3 plays a crucial role in RPE dysfunction by modulating a circAFF3\/p53\/ID2 pathway, suggesting that circAFF3 can serve as a key regulator with therapeutic potential in dry AMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1733888","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:33:10Z","timestamp":1774416790000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CircAFF3 modulation of p53\u2013ID2 signaling in the retinal pigment epithelium links inflammation with cell death in dry age-related macular degeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Yeongseo","family":"Ryu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Chonnam National University Medical School","place":["Hwasun, Jeollanam-do, Republic of Korea"]},{"name":"BioMedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School","place":["Hwasun, Jeollanam-do, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dahee","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chonnam National University Medical School","place":["Hwasun, Jeollanam-do, Republic of Korea"]},{"name":"BioMedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School","place":["Hwasun, Jeollanam-do, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Hun","family":"Kim","sequence":"additional","affiliation":[{"name":"Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital","place":["Seoul, Republic of Korea"]},{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Department of Ophthalmology, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Kook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chonnam National University Medical School","place":["Hwasun, Jeollanam-do, Republic of Korea"]},{"name":"BioMedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School","place":["Hwasun, Jeollanam-do, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","first-page":"31","article-title":"Cell death in age-related macular degeneration","volume":"5","author":"Adler","year":"1999","journal-title":"Mol. 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