{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:02:17Z","timestamp":1791838937031,"version":"4.3.4"},"reference-count":21,"publisher":"American Veterinary Medical Association (AVMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To compare the efficacy of various concentrations and combinations of serum, EDTA, 3 tetracyclines, and <jats:italic>N<\/jats:italic>-acetylcysteine (NAC) for collagenase inhibition in an in vitro corneal degradation model.<\/jats:p>\n<jats:p><jats:bold>SAMPLE<\/jats:bold> Grossly normal corneas from recently euthanized dogs and horses and fresh serum from healthy dogs and horses.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> Serum was pooled by species for in vitro use. For each species, sections of cornea were dried, weighed, and incubated with clostridial collagenase (800 U\/mL) in 5 mL of a 5mM calcium chloride-saline (0.9% NaCl) incubation solution and 500 \u03bcL of 1 of 19 treatments (homologous serum; 0.3%, 1.0%, or 2% EDTA; 0.1%, 0.5%, or 1.0% tetracycline, doxycycline, or minocycline; 0.5%, 1.0%, or 5.0% NAC; serum with 0.5% tetracycline; serum with 1.0% EDTA; or 1.0% EDTA with 0.5% tetracycline). Positive and negative control specimens were incubated with 5 mL of incubation solution with and without collagenase, respectively. Each control and treatment was replicated 4 times for each species. Following incubation, corneal specimens were dried and reweighed. The percentage corneal degradation was calculated and compared among treatments within each species.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> Treatments with tetracyclines at concentrations \u2265 0.5%, with EDTA at concentrations \u2265 0.3%, and with NAC at concentrations \u2265 0.5% were more effective at preventing corneal degradation than serum in both species. The efficacy of each combination treatment was equal to or less than that of its components.<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> Results suggested EDTA, tetracyclines, and NAC may be beneficial for topical treatment of keratomalacia, but in vivo studies are required.<\/jats:p>","DOI":"10.2460\/ajvr.79.5.555","type":"journal-article","created":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T16:08:48Z","timestamp":1524586128000},"page":"555-561","source":"Crossref","is-referenced-by-count":30,"title":["Comparison of the efficacy of various concentrations and combinations of serum, ethylenediaminetetraacetic acid, tetracycline, doxycycline, minocycline, and N-acetylcysteine for inhibition of collagenase activity in an in vitro corneal degradation model"],"prefix":"10.2460","volume":"79","author":[{"given":"Beth A.","family":"Kimmitt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Stiles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"J Cell Physiol","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1002\/jcp.24266","article-title":"\u03b1-2-macroglobulin: a physiological guardian","volume":"228","author":"Rehman","year":"2013"},{"key":"ref2","series-title":"FASEB J","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.1096\/fasebj.6.15.1281457","article-title":"\u03b12-macroglobulin, a multifunctional binding protein with targeting characteristics","volume":"6","author":"Borth","year":"1992"},{"key":"ref3","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1046\/j.1463-5224.2003.00271.x","article-title":"Inhibition of collagenase breakdown of equine corneas by tetanus antitoxin, equine serum and acetylcysteine","volume":"6","author":"Haffner","year":"2003"},{"key":"ref4","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.2460\/ajvr.2003.64.1081","article-title":"Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis","volume":"64","author":"Ollivier","year":"2003"},{"key":"ref5","series-title":"Invest Ophthalmol Vis Sci","first-page":"1569","article-title":"Inhibition of purified collagenase from alkali-burned rabbit corneas","volume":"30","author":"Burns","year":"1989"},{"key":"ref6","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"627","DOI":"10.2460\/ajvr.77.6.627","article-title":"Comparison of the in vitro anti-collagenase efficacy of homologous serum and plasma on degradation of corneas of cats, dogs, and horses","volume":"77","author":"Conway","year":"2016"},{"key":"ref7","series-title":"Acta Ophthalmol","doi-asserted-by":"publisher","first-page":"e605","DOI":"10.1111\/aos.12710","article-title":"Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies","volume":"93","author":"Anitua","year":"2015"},{"key":"ref8","series-title":"Arch Soc Esp Oftalmol","first-page":"376","article-title":"Autologous serum and blood derivatives in ophthalmology","volume":"87","author":"Lopez-Garcia","year":"2012"},{"key":"ref9","series-title":"Agents Actions","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/BF01966597","article-title":"Metal ion-tetracycline interactions in biological fluids. Part 5. Formation of zinc complexes with tetracycline and some of its derivatives and assessment of their biological significance","volume":"17","author":"Brion","year":"1985"},{"key":"ref10","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/j.1463-5224.2008.00662.x","article-title":"Doxycycline levels in preocular tear film of horses following oral administration","volume":"11","author":"Baker","year":"2008"},{"key":"ref11","series-title":"Vet Ophthalmol","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/vop.12479","article-title":"The presence of minocycline in the tear film of normal horses following oral administration and its anticollagenase activity","volume":"21","author":"Monk","year":"2018"},{"key":"ref12","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"508","DOI":"10.2460\/javma.249.5.508","article-title":"Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs","volume":"249","author":"Collins","year":"2016"},{"key":"ref13","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"378","DOI":"10.2460\/javma.237.4.378","article-title":"In vivo effects of adjunctive tetracycline treatment on refractory corneal ulcers in dogs","volume":"237","author":"Chandler","year":"2010"},{"key":"ref14","series-title":"Int Ophthalmol Clin","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1097\/00004397-197501540-00006","article-title":"Collagenase inhibitors: rationale for their use in treating corneal ulceration","volume":"15","author":"Berman","year":"1975"},{"key":"ref15","series-title":"J Ocul Pharmacol Ther","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1089\/jop.2008.0098","article-title":"Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells","volume":"25","author":"Epstein","year":"2009"},{"key":"ref16","series-title":"Eur J Pharm Biopharm","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/S0939-6411(98)00069-1","article-title":"Ocular tolerance of preservatives on the murine cornea","volume":"47","author":"Furrer","year":"1999"},{"key":"ref17","series-title":"Invest Ophthalmol","first-page":"496","article-title":"Characterization and inhibition of corneal collagenase","volume":"10","author":"Hook","year":"1971"},{"key":"ref18","series-title":"Eye (Lond)","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/eye.2012.135","article-title":"Effects of N-acetylcysteine on matrix metalloproteinase-9 secretion and cell migration of human corneal epithelial cells","volume":"26","author":"Ramaesh","year":"2012"},{"key":"ref19","series-title":"Invest Ophthalmol Vis Sci","first-page":"2958","article-title":"Effects of acetylcysteine on rabbit conjunctival and corneal surfaces. A scanning electron microscopy study","volume":"32","author":"Thermes","year":"1991"},{"key":"ref20","series-title":"Ophthalmic Res","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1159\/000074070","article-title":"Effect of acetylcysteine on experimental corneal wounds in dogs","volume":"35","author":"Aldavood","year":"2003"},{"key":"ref21","series-title":"Biochemistry","doi-asserted-by":"publisher","first-page":"7406","DOI":"10.1021\/bi00419a035","article-title":"Preparation and reconstitution with divalent metal ions of class I and class II Clostridium histolyticum apocollagenases","volume":"27","author":"Angleton","year":"1988"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/79\/5\/ajvr.79.5.555.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/79\/5\/ajvr.79.5.555.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/79\/5\/ajvr.79.5.555.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:42:51Z","timestamp":1741351371000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/79\/5\/ajvr.79.5.555.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":21,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.79.5.555","relation":{},"ISSN":["0002-9645"],"issn-type":[{"value":"0002-9645","type":"print"}],"subject":[],"published":{"date-parts":[[2018,5]]}}}