PROX1 loss in adult mouse Schlemm’s canal causes permanent ocular hypertension
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Le résumé fourni par la source
Glaucoma is associated with ocular hypertension and lowering intraocular pressure is a key objective of glaucoma therapies. Recent studies have established a role for the Schlemm's canal endothelium in this pressure increase and have shown it to have a unique, lymphatic-like, hybrid phenotype. However, the role of these lymphatic phenotypes in the adult canal remains uncertain. Long-term functional studies have been limited by systemic importance of lymphatic genes and lack of Schlemm's canal-specific animal models. Here, we designed and validated a strategy using 4OH-tamoxifen-loaded nanocarriers to generate targeted, Schlemm's canal specific knockout mice lacking lymphatic phenotypes. Using this system, we selectively deleted Prox1, the master transcription factor governing lymphatic fate. Within four weeks, intraocular pressure significantly increased, and ocular hypertension was maintained for at least 24 weeks. Unlike lymphatic vessels, which degenerate following Prox1 deletion, Schlemm's canal reverted to a less functional vein-like phenotype with no change in size or morphology. These results highlight the utility of nanocarriers for tissue-specific genetic recombination and demonstrate that changes in lymphatic phenotypes alter intraocular pressure, providing new targets for glaucoma therapy. Moreover, as we found that PROX1 was downregulated with age in human Schlemm's canal, these canal-specific conditional Prox1 knockout mice are a valuable new adult-onset model of ocular hypertension that captures key features of age-related human disease.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- PROX1 loss in adult mouse Schlemm’s canal causes permanent ocular hypertension
- Date Crossref
- 05/05/2026
- Éditeur
- American Society for Clinical Investigation
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Northwestern University Department of Biomedical Engineering pays non établi dans la noticeUniversité ou école supérieure
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Boston University Department of Ophthalmology and Department of Anatomy and Neurobiology pays non établi dans la noticeUniversité ou école supérieure
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Massachusetts Eye and Ear Infirmary pays non établi dans la noticeÉtablissement de santé
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University of Virginia Department of Biomedical Engineering pays non établi dans la noticeUniversité ou école supérieure
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Renal Research Institute pays non établi dans la noticeStructure de recherche
Department of Biomedical Engineering — Northwestern University, Department of Ophthalmology and Department of Anatomy and Neurobiology — Boston University et Massachusetts Eye and Ear Infirmary, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.