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Recent studies have established a key role for Schlemm\u2019s canal endothelium in this pressure increase and have shown that it has a unique, lymphatic-like hybrid phenotype characterized by expression of the lymphatic transcription factor PROX1. However, the functional importance of this hybrid phenotype in the adult canal remains unclear, as long-term studies have been limited by systemic requirements for lymphatic gene expression and a lack of Schlemm\u2019s canal\u2013specific animal models. Here, we designed and validated a51 strategy using 4OH-tamoxifen-loaded nanocarriers to generate targeted, Schlemm\u2019s canal-52 specific\n                    <jats:italic>Prox1<\/jats:italic>\n                    knockout mice that specifically lacked lymphatic characteristics in the canal53 endothelium. Within 4 weeks, intraocular pressure was significantly elevated, and ocular hypertension was maintained for at least 24 weeks. Unlike lymphatic vessels, which degenerate following\n                    <jats:italic>Prox1<\/jats:italic>\n                    deletion, Schlemm\u2019s canal persisted but reverted to a less functional vein-like phenotype with no change in size or morphology. Together, these findings demonstrate the utility of nanocarrier-mediated tamoxifen delivery and establish the importance of the Schlemm\u2019s canal lymphatic-like phenotype in intraocular pressure regulation, providing targets for future glaucoma therapies and a mouse model of adult-onset ocular hypertension.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.203711","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:00:31Z","timestamp":1777996831000},"source":"Crossref","is-referenced-by-count":0,"title":["PROX1 loss in adult mouse Schlemm\u2019s canal causes permanent ocular hypertension"],"prefix":"10.1172","volume":"11","author":[{"given":"Sofia","family":"Lara Ochoa","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoi-Lam","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeohn","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihang","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia C.","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, 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