{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:12:48Z","timestamp":1789827168735,"version":"4.0.1"},"reference-count":42,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"General Projects of Department of science and Technology of Shaanxi Province","award":["2024SF-YBXM-334"],"award-info":[{"award-number":["2024SF-YBXM-334"]}]},{"name":"Key Research and Development Program of Shaanxi","award":["2023-YBSF-586"],"award-info":[{"award-number":["2023-YBSF-586"]}]},{"name":"Natural Science Basic Research Plan of Shaanxi Province of China","award":["2017JM8043"],"award-info":[{"award-number":["2017JM8043"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Benzalkonium chloride (BAK), a quaternary ammonium antimicrobial agent widely utilized in ophthalmic formulations, is associated with chronic ocular surface toxicity. BAK induces corneal epithelial inflammation and autophagic impairment, yet their interrelationship remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Mouse corneal epithelial cell lines (MCECs) were subjected to short-term BAK exposure (10\u201320 \u03bcg\/mL, 15 min + 8 h recovery). TLR4\/MyD88\/NF-\u03baB pathway activation and proinflammatory cytokines (Il-1\u03b1, Il-1\u03b2, Il-6) were assessed. Autophagic flux was evaluated via LC3-II\/I ratio, p62 accumulation, GFP-RFP-LC3 autolysosome formation assay, and lysosomal function. Pharmacological interventions with rapamycin (mTOR blockade) and TAK-242 (TLR4 inhibition) were used to dissect pathway interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Short-term BAK exposure dose-dependently activated the TLR4\/MyD88\/NF-\u03baB pathway and elevated proinflammatory cytokines. Concurrently, BAK inhibited autophagic flux through mTOR hyperactivation, evidenced by reduced LC3-II\/I ratio, p62 accumulation, impaired autolysosome formation, and lysosomal dysfunction. Both rapamycin and TAK-242 significantly attenuated BAK-induced MyD88\/NF-\u03baB activation and inflammation. Critically, BAK activates parallel TLR4-MyD88 and mTOR pathways that synergistically amplify NF-\u03baB signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>These results unveil mTOR as a therapeutic target for mitigating BAK-induced corneal damage, thereby proposing mTOR suppression or autophagic activation as viable interventions for BAK-associated ocular surface disorders. Particularly at lower concentration (0.001%) and shorter exposure (15 min) of BAK.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10807683261486972","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:56:14Z","timestamp":1789635374000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["mTOR\/Autophagy\/\/NF-\u03baB Axis Drives Benzalkonium Chloride-Induced Inflammatory Response in Corneal Epithelial Cells"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8090-629X","authenticated-orcid":false,"given":"Jing","family":"Du","sequence":"first","affiliation":[{"name":"Shaanxi Eye Hospital, Xi\u2019an People\u2019s Hospital (Xi\u2019an Fourth Hospital), Affiliated People\u2019s Hospital, Northwest University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0783-4179","authenticated-orcid":false,"given":"Zhe","family":"Yu","sequence":"additional","affiliation":[{"name":"Shaanxi Eye Hospital, Xi\u2019an People\u2019s Hospital (Xi\u2019an Fourth Hospital), Affiliated People\u2019s Hospital, Northwest University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Shaanxi Eye Hospital, Xi\u2019an People\u2019s Hospital (Xi\u2019an Fourth Hospital), Affiliated People\u2019s Hospital, Northwest University, Xi\u2019an, China."},{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Shaanxi Eye Hospital, Xi\u2019an People\u2019s Hospital (Xi\u2019an Fourth Hospital), Affiliated People\u2019s Hospital, Northwest University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengsheng","family":"Wei","sequence":"additional","affiliation":[{"name":"Shaanxi Eye Hospital, Xi\u2019an People\u2019s Hospital (Xi\u2019an Fourth Hospital), Affiliated People\u2019s Hospital, Northwest University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Shaanxi Eye Hospital, Xi\u2019an People\u2019s Hospital (Xi\u2019an Fourth Hospital), Affiliated People\u2019s Hospital, Northwest University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Optometry Teaching and Research Section, College of Medical Technology, Xi\u2019 an Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"issue":"2","key":"e_1_3_2_2_1","first-page":"e54028","article-title":"Dry eye disease: An overview of its risk factors, diagnosis, and prevalence by age, sex, and race","volume":"16","author":"Deo N","year":"2024","unstructured":"1.Deo N, , Nagrale P. 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