| First Author | Lara Ochoa S | Year | 2026 |
| Journal | JCI Insight | Volume | 11 |
| Issue | 12 | PubMed ID | 42084939 |
| Mgi Jnum | J:391818 | Mgi Id | MGI:8369955 |
| Doi | 10.1172/jci.insight.203711 | Citation | Lara Ochoa S, et al. (2026) PROX1 loss in adult mouse Schlemm's canal causes permanent ocular hypertension. JCI Insight 11(12) |
| abstractText | Glaucoma is associated with ocular hypertension, and lowering intraocular pressure is the primary objective of current therapies. Recent studies have established a key role for Schlemm's 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's canal-specific animal models. Here, we designed and validated a51 strategy using 4OH-tamoxifen-loaded nanocarriers to generate targeted, Schlemm's canal-52 specific Prox1 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 Prox1 deletion, Schlemm's 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's canal lymphatic-like phenotype in intraocular pressure regulation, providing targets for future glaucoma therapies and a mouse model of adult-onset ocular hypertension. |
