{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:01:00Z","timestamp":1780470060995,"version":"3.54.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007259","name":"Stony Brook University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007259","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Drug Deliv."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The symptoms of dry eye disease (DED) result from activation of ocular sensory nerves and constitute the dominant component of its clinical presentation. We assessed the effect of phosphosulindac (PS), a small molecule efficacious in the treatment of DED in preclinical models, on corneal sensitivity (CS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CS was determined with a Cochet-Bonnet esthesiometer in New Zealand white (NZW) and Dutch-belted black (DBB) rabbits. DED was induced by Concanavalin A injections into the rabbits\u2019 lacrimal glands. Changes in CS, tear osmolarity, tear break up time (TBUT) and Schirmer tear test were measured before and after DED induction. PS in various formulations (emulsions, nanoparticles and hydrogels) and other ocular drugs were applied in eye drop form to normal rabbits and those with DED.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>nduction of DED caused a decrease in the CS, TBUT time as measured by fluorescein dye, in tear production as measured by Schirmer\u2019s tear test and an increase in tear osmolarity. PS markedly restored the suppressed CS in dry eyes. The effect was immediate, fully reversible, lasted \u223c26\u00a0h and appeared dissociated from its anti-inflammatory properties. The most efficacious formulation was a Carbopol-based hydrogel; cyclodextrin-based and emulsion formulations were also effective. The most optimal dose of PS was 0.2% and the optimal pH was 6.2. None of 7 compounds structurally related to PS affected CS nor did cyclosporine, lifitegrast and artificial tears. PS does not have an anesthetic effect on the cornea. In normal eyes, PS suppressed CS and this effect was concentration-, formulation-, and pH-dependent. Two non-steroidal anti-inflammatory drugs (NSAIDs), ketorolac and bromfenac, and lidocaine suppressed CS in normal but not in dry eyes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PS restores the suppressed CS in dry eyes possiblely by a direct effect on corneal nerves. This effect appears unique to PS, distinct from all tested compounds including the two currently approved drugs for DED. PS, in addition to affecting CS of DED, may improve its symptoms and merits further evaluation for the treatment of DED.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fddev.2026.1778440","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:01:47Z","timestamp":1780466507000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphosulindac (OXT-328) restores the suppressed corneal sensitivity in rabbits with dry eye disease: therapeutic implications"],"prefix":"10.3389","volume":"6","author":[{"given":"Wei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Stony Brook University","place":["Stony Brook, NY, United States"]},{"name":"Department of Medicine, Stony Brook University","place":["Stony Brook, NY, United States"]},{"name":"Department of Cornea and Ocular Surface, Changsha Aier Eye Hospital","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stony Brook University","place":["Stony Brook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Tourmouzis","sequence":"additional","affiliation":[{"name":"Barts and the London School of Medicine and Dentistry","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stony Brook University","place":["Stony Brook, NY, United States"]},{"name":"Medicon Pharmaceuticals, Inc.","place":["Setauket, NY, United States"]},{"name":"Apis Therapeutics LLC","place":["Setauket, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanford M.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Apis Therapeutics LLC","place":["Setauket, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Natke","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stony Brook University","place":["Stony Brook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Honkanen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stony Brook University","place":["Stony Brook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil","family":"Rigas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stony Brook University","place":["Stony Brook, NY, United States"]},{"name":"Department of Preventive Medicine, Stony Brook University","place":["Stony Brook, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/s0008-4182(04)80071-1","article-title":"Correlation between corneal sensitivity, subjective dry eye symptoms and corneal staining in sjogren's syndrome","volume":"39","author":"Adatia","year":"2004","journal-title":"Can. 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