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This study evaluated the potential of pirfenidone (PFD), an FDA-approved drug, to inhibit inflammation in the human cornea using an\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Healthy cadaver human corneas and standard\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      corneal inflammation models were used. Primary human corneal stromal fibroblasts (hCSFs) generated from donor corneas were used in the entire study. The dose-dependent assays identified optimal lipopolysaccharide (LPS; 0\u2013150 ng\/ml) concentration to induce inflammation and PFD\u2019s (0\u2013500 \u00b5g\/mL) half-maximal inhibitory concentration (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) to hCSF. The quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, Western blotting, and reactive oxygen species (ROS) commercial kits studied changes in inflammatory response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A significant upregulation of inflammatory markers in hCSF at 48 h was noted at 50 ng\/ml of LPS concentration. The IC\n                      <jats:sub>50<\/jats:sub>\n                      of PFD was found to be 200 \u00b5g\/mL for hCSFs. Topical treatments of PFD (200 \u00b5g\/mL) significantly reduced LPS (50 \u00b5g\/mL)-induced levels of pro-inflammatory (TNF\u03b1, IL1\u03b1, IL1\u03b2, IL6, and cyclooxygenase 2) markers and oxidative stress (glutathione peroxidase 1 [GPX1], GPX4, and catalase) genes (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001 or\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.0001) in human corneas\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Moreover, PFD significantly inhibited LPS-increased ROS production (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001) in hCSF. PFD treatment reduced LPS-induced inflammatory stimulation and tumor necrosis factor alpha and I\u03baB alpha phosphorylation in hCSF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      PFD inhibits corneal inflammation\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      by reducing pro-inflammatory cytokines and oxidative stress. Comprehensive preclinical animal testing is warranted to define the potential of PFD to treat corneal symptoms\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      in traumatic eyes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10807683261452067","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T16:30:21Z","timestamp":1780072221000},"page":"556-563","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pirfenidone Inhibits Inflammatory Mediators in Human Cornea\n                    <i>In Vitro<\/i>"],"prefix":"10.1177","volume":"42","author":[{"given":"Alexandria C.","family":"Hofmann","sequence":"first","affiliation":[{"name":"Harry S. Truman Memorial Veterans\u2019 Hospital, Columbia, Missouri, USA."},{"name":"Mason Eye Institute, School of Medicine, University of Missouri, Columbia, Missouri, United States."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4660-5534","authenticated-orcid":false,"given":"Nishant R.","family":"Sinha","sequence":"additional","affiliation":[{"name":"Harry S. 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