{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:37:21Z","timestamp":1788813441244,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The association between modern lifestyle factors and dry eye disease (DED) pathogenesis has garnered increasing scientific attention. Emerging evidence implicates circadian disruption\u2014a prevalent consequence of contemporary living patterns\u2014as a significant yet not fully clarified pathogenic factor in DED development. To address this knowledge gap, we developed a circadian disruption mouse model using chronic jet lag exposure. Mice subjected to chronic jet lag exhibited conjunctival clock gene dysregulation and upregulated pro\u2010inflammatory mediators, such as TNF\u2010\u03b1, IL\u20106, and IL\u201017. Transcriptomic profiling demonstrated marked activation of IL\u201017\u2010mediated inflammatory pathways within the conjunctival tissue. Therapeutic IL\u201017 neutralization substantially attenuated ocular surface inflammation, improved corneal epithelial integrity, and decreased apoptotic cell density in circadian disruption\u2010induced dry eye mouse model. Moreover, REV\u2010ERB\u03b1 agonism potently suppressed IL\u201017 transcription, whereas BMAL1 deficiency exacerbated IL\u201017\u2010driven inflammatory responses through REV\u2010ERB\u03b1 downregulation. Chronic jet lag additionally induced ocular surface microbiota dysbiosis, characterized by Firmicutes overproliferation. Melatonin administration effectively suppressed conjunctival IL\u201017 expression through BMAL1\u2010REV\u2010ERB\u03b1 pathway activation while reducing the relative abundance of Firmicutes to restore ocular surface microbiota balance. Our study reveals that circadian disruption induces ocular surface inflammation through the BMAL1\u2010REV\u2010ERB\u03b1\u2010IL\u201017 signaling axis and exacerbates dysbiosis of the ocular surface microbiota. Melatonin mitigates these pathological alterations via dual\u2010directional modulation of circadian\u2010immune signaling crosstalk and restoration of microbiota balance. Importantly, this study establishes melatonin as a multifaceted therapeutic agent for combating lifestyle\u2010associated DED, while elucidating the underlying mechanisms governing circadian rhythm\u2010microbiome axis dynamics in ocular surface pathogenesis.<\/jats:p>","DOI":"10.1111\/jpi.70076","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T08:12:13Z","timestamp":1757664733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Melatonin Ameliorates Circadian Disruption\u2010Associated Dry Eye via Modulation of BMAL1\u2010REV\u2010ERB\u03b1\u2010IL\u201017 Axis and Ocular Surface Microbiota Homeostasis"],"prefix":"10.1111","volume":"77","author":[{"given":"Bowen","family":"Wang","sequence":"first","affiliation":[{"name":"Beijing Tongren Eye Center, Beijing Tongren Hospital Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences  Beijing 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