{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:09:17Z","timestamp":1779242957025,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T00:00:00Z","timestamp":1458086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We examined the effect of all\u2010<jats:italic>trans<\/jats:italic> retinoic acid on collagen degradation mediated by corneal fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rabbit corneal fibroblasts were cultured with or without all\u2010<jats:italic>trans<\/jats:italic> retinoic acid in a three\u2010dimensional collagen gel, and the extent of collagen degradation was determined by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Matrix metalloproteinase expression was examined by immunoblot analysis and gelatin zymography. The abundance and phosphorylation state of the endogenous nuclear factor\u2010kappaB inhibitor I\u03baB\u2010\u03b1 were examined by immunoblot analysis. Corneal ulceration was induced by injection of lipopolysaccharide into the central corneal stroma of rabbits and was assessed by observation with a slitlamp microscope.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All\u2010<jats:italic>trans<\/jats:italic> retinoic acid inhibited interleukin\u20101\u03b2\u2010induced collagen degradation by corneal fibroblasts in a concentration\u2010 and time\u2010dependent manner. It also attenuated the release and activation of matrix metalloproteinases as well as the phosphorylation and degradation of I\u03baB\u2010\u03b1 induced by interleukin\u20101\u03b2 in these cells. Topical application of all\u2010<jats:italic>trans<\/jats:italic> retinoic acid suppressed corneal ulceration induced by injection of lipopolysaccharide into the corneal stroma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>All\u2010<jats:italic>trans<\/jats:italic> retinoic acid inhibited collagen degradation mediated by corneal fibroblasts exposed to interleukin\u20101\u03b2, with this effect being accompanied by suppression of nuclear factor\u2010kappaB signalling as well as of matrix metalloproteinase release and activation in these cells. All\u2010<jats:italic>trans<\/jats:italic> retinoic acid also attenuated lipopolysaccharide\u2010induced corneal ulceration in vivo. Our results therefore suggest that all\u2010<jats:italic>trans<\/jats:italic> retinoic acid might prove effective for the treatment of patients with corneal ulceration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.12709","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T13:48:38Z","timestamp":1454420918000},"page":"502-508","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition by all\u2010<i>trans<\/i> retinoic acid of collagen degradation mediated by corneal fibroblasts"],"prefix":"10.1111","volume":"44","author":[{"given":"Kazuhiro","family":"Kimura","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Yamaguchi University, Graduate School of Medicine  Yamaguchi Japan"},{"name":"Senju Pharmaceutical Co.  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