{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T07:23:06Z","timestamp":1787383386336,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009944","name":"American College of Veterinary Ophthalmologists Vision for Animals Foundation","doi-asserted-by":"publisher","award":["VAF2023\u20101"],"award-info":[{"award-number":["VAF2023\u20101"]}],"id":[{"id":"10.13039\/100009944","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Ophthalmology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Corneal fibrosis is a leading cause of blindness in mammalian species and may result in compromised performance in sports and daily functions. This study evaluated the safety and anti\u2010fibrotic effects of the FDA\u2010approved drugs, angiotensin\u2010converting enzyme inhibitor (ACE\u2010I) lisinopril and rho\u2010kinase inhibitor (ROCK\u2010I) fasudil, alone and in combination, on the canine cornea using an established in\u00a0vitro model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To test the safety and efficacy of lisinopril and fasudil, primary canine corneal fibroblasts (CCFs) generated from donor corneas of healthy dogs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920) were used. A series of dose\u2010dependent and time\u2010dependent assays with lisinopril (1\u201350\u2009\u03bcM) and fasudil (1\u201310\u2009nM) were performed. qRT\u2010PCR, immunofluorescence (IF) staining, cell viability assay, cell proliferation assay, LIVE\/DEAD viability\/cytotoxicity assay, TUNEL assay, and total cell count were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A 25\u2010\u03bcM lisinopril and 3\u2010nM fasudil dose were safe, nontoxic, and optimal for therapeutic evaluations in\u00a0vitro. Treatments of lisinopril or fasudil, alone or in\u2010combination, to CCFs grown in the presence of TGF\u2010\u03b21 (5\u2009ng\/mL) showed inhibition of myofibroblast formation based on phase\u2010contrast microscopy. The qRT\u2010PCR and IF studies showed a significant decrease in expression of profibrotic markers, including \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001), fibronectin (FN;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.0002), tenascin C (TNC;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001), Collagen I (Col\u2010I;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001), Collagen IIIA1 (Co\u2010IIIA1;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001), and Collagen IV (Co\u2010lV;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>An ophthalmic formulation consisting of lisinopril and fasudil may offer a safe and effective method to treat canine corneal fibrosis. Additional studies evaluating safety and efficacy of this formulation in\u00a0vivo are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/vop.13304","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T21:14:28Z","timestamp":1732655668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Anti\u2010fibrotic effects of lisinopril (\n                    <scp>ACE<\/scp>\n                    inhibitor) and fasudil (\n                    <scp>ROCK<\/scp>\n                    inhibitor) in combination for canine corneal fibrosis in\u00a0vitro"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2045-2023","authenticated-orcid":false,"given":"Brayden L.","family":"Routh","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, One\u2010Health One\u2010Medicine Ophthalmology and Vision Research Center University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7398-8115","authenticated-orcid":false,"given":"Ratnakar","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, One\u2010Health One\u2010Medicine Ophthalmology and Vision Research Center University of Missouri  Columbia Missouri USA"},{"name":"Harry S. 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