ArticleThe Journal of clinical investigation2025
Endothelial cell-specific postnatal deletion of Nos3 preserves intraocular pressure homeostasis via macrophage recruitment and NOS2 upregulation.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Schlemm's Canal Development and Implications for Glaucoma Treatment.Annual review of vision science · 2026Review
- Engineering a Membrane-Anchored CreER Recombinase With Reduced Basal Activity for In Vitro Recombination.Biotechnology journal · 2026Article
- Principles of resident tissue macrophages revealed by the eye.Advances in immunology · 2026Review
- Intracameral Puncture Lowers Intraocular Pressure and Triggers an Immune Response in the Conventional Outflow Tract.Investigative ophthalmology & visual science · 2025Article
- Glaucoma discovery on a chip.Nature cardiovascular research · 2025Article
- Glaucoma and cardiovascular disease: a bidirectional two-sample Mendelian randomization analysis.Experimental biology and medicine (Maywood, N.J.) · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
Polymorphisms in Nos3 increase risk for glaucoma, the leading cause of irreversible blindness worldwide. A key modifiable risk factor for glaucoma is intraocular pressure (IOP), which is regulated by NO - a product of nitric oxide synthase 3 (encoded by Nos3) - in Schlemm's canal of the conventional outflow pathway. We studied the effects of a conditional, endothelial cell-specific postnatal deletion of Nos3 (Endo-SclCre-ERT;Nos3fl/fl) on tissues of the outflow pathway. We observed that Cre-ERT expression spontaneously and gradually increased with time in vascular endothelia including in Schlemm's canal, beginning at P10, with complete Nos3 deletion occurring around P90. Whereas outflow resistance was reduced in global Nos3-KO mice, outflow resistance and IOP in Endo-SclCre-ERT;Nos3fl/fl mice were normal. We observed - coincident with Nos3 deletion - recruitment of macrophages to and induction of both ELAM1 and NOS2 expression by endothelia in the distal portion of the outflow pathway, which increased vessel diameter. These adjustments reduced outflow resistance to maintain IOP in these Endo-SclCre-ERT;Nos3fl/fl mice. Selective inhibition of iNOS by 1400W resulted in narrowing of distal vessels and IOP elevation. Together, the results emphasize the pliability of the outflow system and the importance of NO signaling in IOP control, and imply an substantial role for macrophages in IOP homeostasis.
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Registered trials
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