{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:02:32Z","timestamp":1777903352078,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":363,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20211052"],"award-info":[{"award-number":["BK20211052"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018636","name":"Xuzhou Science and Technology Program","doi-asserted-by":"publisher","award":["KC23071"],"award-info":[{"award-number":["KC23071"]}],"id":[{"id":"10.13039\/501100018636","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ophthalmology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      The purpose of this study was to explore the protective effect of caffeine on oxidative damage of RPE cells and NaIO\n                      <jats:sub>3<\/jats:sub>\n                      \u2010induced retinal degeneration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      was used to induce the oxidative damage in ARPE\u201019 cells. Cell viability was measured by the CCK\u20108 assay. The morphology of ARPE\u201019 cells was observed by optical microscope. The apoptosis of ARPE\u201019 cells was analyzed by Annexin V\/PI staining, and DNA fragmentation was detected using the TUNEL assay. The protein levels of apoptosis markers BAX and BCL2 as well as senescence marker p21 were detected by Western blot. DNA damage was indicated by immunofluorescence staining of \u03b3\u2010H2AX and observed by fluorescence microscopy. Transcriptome profiling of ARPE\u201019 cells was performed by RNA\u2010seq.\n                      <jats:italic>In vivo<\/jats:italic>\n                      model of retinal oxidative damage was constructed by injecting NaIO\n                      <jats:sub>3<\/jats:sub>\n                      into the tail vein of C57BL\/6 mice. H&amp;E staining was performed after removing the eyeballs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The CCK\u20108 assay showed that caffeine could significantly increase the cell viability inhibited by 200\u2009\u03bcM H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      . Caffeine significantly reduced H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      \u2010induced DNA fragmentation and apoptosis in ARPE\u201019 cells, as demonstrated by the TUNEL assay and Annexin V\/PI staining. The results of Western blot showed that caffeine modulated key proteins associated with apoptosis by decreasing BAX and p21 levels while increasing BCL2 expression in H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      \u2010treated ARPE\u201019 cells, thereby suggesting its cytoprotective effects. In terms of mechanism, caffeine reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) produced by H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      . Caffeine treatment attenuated the accumulation of \u03b3\u2010H2AX, a marker of DNA damage, in ARPE\u201019 cells. Importantly, transcriptome profiling revealed that caffeine might affect complement cascade and lipid metabolism in H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      \u2010treated ARPE\u201019 cells. Finally,\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiment suggested that chronic administration of caffeine could alleviate oxidative damage of the RPE layer and improve the structure of the entire retina in mice with NaIO\n                      <jats:sub>3<\/jats:sub>\n                      \u2010induced retinal degeneration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Caffeine can reduce oxidative damage of RPE cells and improve NaIO\n                      <jats:sub>3<\/jats:sub>\n                      \u2010induced retinal degeneration.\n                    <\/jats:p>\n                  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