{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:18:14Z","timestamp":1792642694237,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>Dry eye disease (DED) is an emerging health issue affecting people worldwide. There have been rapid advances in the development of novel molecules and targeted therapies for the treatment of DED in the recent past. For testing and optimizing these therapies, it is necessary to have reliable experimental animal models of DED. One such approach is the use of benzalkonium chloride (BAC). Several BAC-induced DED models of rabbits and mice have been described in literature. BAC induces high levels of proinflammatory cytokines in the cornea and conjunctiva, along with epithelial cell apoptosis and reduction of mucins, which leads to tear film instability, thereby successfully simulating human DED. The stability of these models directs whether the treatment is to be applied while BAC is being instilled or after its cessation. In this review, we summarize the previously described BAC animal models of DED and present original data on rabbit DED models created using 0.1%, 0.15%, and 0.2% BAC administration twice daily for two consecutive weeks. The 0.2% BAC model sustained DED signs for 3 weeks, while 0.1% and 0.15% models sustained DED signs for 1\u20132 weeks after BAC discontinuation. Overall, these models look promising and continue to be used in various studies to investigate the efficacy of therapeutic drugs for DED treatment.<\/jats:p>","DOI":"10.4103\/ijo.ijo_2791_22","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T11:10:52Z","timestamp":1680952252000},"page":"1256-1262","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Benzalkonium chloride-induced dry eye disease animal models: Current understanding and potential for translational research"],"prefix":"10.4103","volume":"71","author":[{"given":"Minal","family":"Thacker","sequence":"first","affiliation":[{"name":"Brien Holden Center for Eye Research (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India"},{"name":"Centre for Ocular Regeneration, L V Prasad Eye Institute, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Brien Holden Center for Eye Research (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India"},{"name":"Centre for Ocular Regeneration, L V Prasad Eye Institute, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Aniruth","family":"Reddy","sequence":"additional","affiliation":[{"name":"Brien Holden Center for Eye Research (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran K","family":"Bokara","sequence":"additional","affiliation":[{"name":"CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Singh","sequence":"additional","affiliation":[{"name":"Brien Holden Center for Eye Research (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India"},{"name":"Ophthalmic Plastic Surgery Services, LV Prasad Eye Institute, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayan","family":"Basu","sequence":"additional","affiliation":[{"name":"Brien Holden Center for Eye Research (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India"},{"name":"The Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Singh","sequence":"additional","affiliation":[{"name":"Brien Holden Center for Eye Research (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India"},{"name":"Centre for Ocular Regeneration, L V Prasad Eye Institute, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"R1-20240828","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jtos.2019.02.007","article-title":"Incidence, demographics, types and risk factors of dry eye disease in India:Electronic medical records driven big data analytics report I","volume":"17","author":"Donthineni","year":"2019","journal-title":"Ocul Surf"},{"key":"R2-20240828","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II Definition and Classification Report","volume":"5","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"key":"R3-20240828","doi-asserted-by":"crossref","first-page":"108538","DOI":"10.1016\/j.exer.2021.108538","article-title":"Rabbit models of dry eye disease:Current understanding and unmet needs for translational research","volume":"206","author":"Singh","year":"2021","journal-title":"Exp Eye Res"},{"key":"R4-20240828","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/ICO.0000000000001867","article-title":"Impact of nanostructured lipid carriers as an artificial tear film in a rabbit evaporative dry eye model","volume":"38","author":"Niamprem","year":"2019","journal-title":"Cornea"},{"key":"R5-20240828","first-page":"660","article-title":"In vivo biomicroscopy and photography of meibomian glands in a rabbit model of meibomian gland dysfunction","volume":"22","author":"Jester","year":"1982","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R6-20240828","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1080\/02713683.2019.1594933","article-title":"A new rabbit model of chronic dry eye disease induced by complete surgical dacryoadenectomy","volume":"44","author":"Honkanen","year":"2019","journal-title":"Curr Eye Res"},{"key":"R7-20240828","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jtos.2018.05.004","article-title":"Subconjunctival dendrimer-drug therapy for the treatment of dry eye in a rabbit model of induced autoimmune dacryoadenitis","volume":"16","author":"Lin","year":"2018","journal-title":"Ocul Surf"},{"key":"R8-20240828","doi-asserted-by":"crossref","first-page":"8290","DOI":"10.1038\/s41598-017-08197-2","article-title":"Lacrimal gland repair after short-term obstruction of excretory duct in rabbits","volume":"7","author":"Lin","year":"2017","journal-title":"Sci Rep"},{"key":"R9-20240828","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1167\/iovs.07-0720","article-title":"A rabbit dry eye model induced by topical medication of a preservative benzalkonium chloride","volume":"49","author":"Xiong","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R10-20240828","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41433-021-01668-x","article-title":"Ocular benzalkonium chloride exposure:Problems and solutions","volume":"36","author":"Goldstein","year":"2022","journal-title":"Eye (Lond)"},{"key":"R11-20240828","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.preteyeres.2010.03.001","article-title":"Preservatives in eyedrops:The good, the bad and the ugly","volume":"29","author":"Baudouin","year":"2010","journal-title":"Prog Retin Eye Res"},{"key":"R12-20240828","doi-asserted-by":"crossref","first-page":"e40893","DOI":"10.1371\/journal.pone.0040893","article-title":"Localization and expression of zonula occludins-1 in the rabbit corneal epithelium following exposure to benzalkonium chloride","volume":"7","author":"Chen","year":"2012","journal-title":"PLoS One"},{"key":"R13-20240828","first-page":"361","article-title":"Cytotoxicity of ophthalmic preservatives on human corneal epithelium","volume":"9","author":"Tripathi","year":"1992","journal-title":"Lens Eye Toxic Res"},{"key":"R14-20240828","first-page":"257","article-title":"A mouse dry eye model induced by topical administration of benzalkonium chloride","volume":"17","author":"Lin","year":"2011","journal-title":"Mol Vis"},{"key":"R15-20240828","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1089\/jop.2013.0129","article-title":"Comparison of prednisolone acetate and loteprednol etabonate for the treatment of benzalkonium chloride-induced dry eye syndrome in rats","volume":"30","author":"Beyazyildiz","year":"2014","journal-title":"J Ocul Pharmacol Ther"},{"key":"R16-20240828","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1167\/iovs.03-1055","article-title":"Animal models of dry eye:A critical assessment of opportunities and limitations","volume":"45","author":"Barabino","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R17-20240828","doi-asserted-by":"crossref","first-page":"635","DOI":"10.18240\/ijo.2022.04.18","article-title":"Transgenic dry eye mouse models:Powerful tools to study dry eye disease","volume":"15","author":"Qin","year":"2022","journal-title":"Int J Ophthalmol"},{"key":"R18-20240828","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.transci.2015.05.016","article-title":"Animal models to assess the therapeutic efficacy of human serum and serum-converted platelet lysates for dry eye syndrome:Seeing is believing","volume":"53","author":"Tseng","year":"2015","journal-title":"Transfus Apher Sci"},{"key":"R19-20240828","doi-asserted-by":"crossref","first-page":"e33688","DOI":"10.1371\/journal.pone.0033688","article-title":"Research on the stability of a rabbit dry eye model induced by topical application of the preservative benzalkonium chloride","volume":"7","author":"Li","year":"2012","journal-title":"PLoS One"},{"key":"R20-20240828","doi-asserted-by":"crossref","first-page":"7204951","DOI":"10.1155\/2020\/7204951","article-title":"Optimization of a rabbit dry eye model induced by topical instillation of benzalkonium chloride","volume":"2020","author":"Carpena-Torres","year":"2020","journal-title":"J Ophthalmol"},{"key":"R21-20240828","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.3390\/polym12071465","article-title":"Mucoadhesive Bletilla striata polysaccharide-based artificial tears to relieve symptoms and inflammation in rabbit with dry eyes syndrome","volume":"12","author":"Thacker","year":"2020","journal-title":"Polymers (Basel)"},{"key":"R22-20240828","doi-asserted-by":"crossref","first-page":"11999","DOI":"10.3390\/ijms222111999","article-title":"Efficacy of artificial tears based on an extract of artemia salina containing dinucleotides in a rabbit dry eye model","volume":"22","author":"Carpena-Torres","year":"2021","journal-title":"Int J Mol Sci"},{"key":"R23-20240828","doi-asserted-by":"crossref","first-page":"e0157982","DOI":"10.1371\/journal.pone.0157982","article-title":"Synergistic effect of artificial tears containing epigallocatechin gallate and hyaluronic acid for the treatment of rabbits with dry eye syndrome","volume":"11","author":"Tseng","year":"2016","journal-title":"PLoS One"},{"key":"R24-20240828","doi-asserted-by":"crossref","first-page":"e0153573","DOI":"10.1371\/journal.pone.0153573","article-title":"Solvent\/Detergent virally inactivated serum eye drops restore healthy ocular epithelium in a rabbit model of dry-eye syndrome","volume":"11","author":"Tseng","year":"2016","journal-title":"PLoS One"},{"key":"R25-20240828","doi-asserted-by":"crossref","first-page":"913","DOI":"10.3109\/02713683.2014.969810","article-title":"Combining sodium hyaluronate and polyvinylpyrrolidone therapies for the rabbit cornea:A new approach to relief of the human dry eye syndrome","volume":"40","author":"Ehrenberg","year":"2015","journal-title":"Curr Eye Res"},{"key":"R26-20240828","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1080\/02713683.2018.1563702","article-title":"The efficiency of cyclosporine a-eluting contact lenses for the treatment of dry eye","volume":"44","author":"Choi","year":"2019","journal-title":"Curr Eye Res"},{"key":"R27-20240828","doi-asserted-by":"crossref","first-page":"5580","DOI":"10.1039\/C9NR00376B","article-title":"Synergistically dual-functional nano eye-drops for simultaneous anti-inflammatory and anti-oxidative treatment of dry eye disease","volume":"11","author":"Li","year":"2019","journal-title":"Nanoscale"},{"key":"R28-20240828","first-page":"284","article-title":"The leaves of Diospyros kaki exert beneficial effects on a benzalkonium chloride-induced murine dry eye model","volume":"22","author":"Kim","year":"2016","journal-title":"Mol Vis"},{"key":"R29-20240828","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jep.2017.12.041","article-title":"A standardized extract of Rhynchosia volubilis Lour. exerts a protective effect on benzalkonium chloride-induced mouse dry eye model","volume":"215","author":"Kang","year":"2018","journal-title":"J Ethnopharmacol"},{"key":"R30-20240828","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.exer.2013.06.005","article-title":"Amniotic membrane extract ameliorates benzalkonium chloride-induced dry eye in a murine model","volume":"115","author":"Xiao","year":"2013","journal-title":"Exp Eye Res"},{"key":"R31-20240828","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.3390\/pharmaceutics13091366","article-title":"Effects of eye drops containing hyaluronic acid-nimesulide conjugates in a benzalkonium chloride-induced experimental dry eye rabbit model","volume":"13","author":"Chen","year":"2021","journal-title":"Pharmaceutics"},{"key":"R32-20240828","doi-asserted-by":"crossref","first-page":"e14352","DOI":"10.1111\/jfbc.14352","article-title":"Capsanthin from Capsicum annum fruits exerts anti-glaucoma, antioxidant, anti-inflammatory activity, and corneal pro-inflammatory cytokine gene expression in a benzalkonium chloride-induced rat dry eye model","volume":"46","author":"Shanmugham","year":"2022","journal-title":"J Food Biochem"},{"key":"R33-20240828","doi-asserted-by":"crossref","first-page":"e0224805","DOI":"10.1371\/journal.pone.0224805","article-title":"Cyclosporine A eyedrops with self-nanoemulsifying drug delivery systems have improved physicochemical properties and efficacy against dry eye disease in a murine dry eye model","volume":"14","author":"Bang","year":"2019","journal-title":"PLoS One"}],"container-title":["Indian Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/IJO.IJO_2791_22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:26:48Z","timestamp":1786724808000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/IJO.IJO_2791_22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.4103\/ijo.ijo_2791_22","relation":{},"ISSN":["0301-4738","1998-3689"],"issn-type":[{"value":"0301-4738","type":"print"},{"value":"1998-3689","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"2022-10-24","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-16","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}