| eNOS, a pressure-dependent regulator of intraocular pressure. | |
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MedLine Citation:
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PMID: 22039240 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Pathology in the primary drainage pathway for aqueous humor in the eye is responsible for ocular hypertension, the only treatable risk factor in patients with glaucoma. Unfortunately, the mechanisms that regulate pressure-dependent drainage of aqueous humor and thus intraocular pressure (IOP) are unknown. To better understand one possible underlying molecular factor that regulates IOP, nitric oxide (NO), pressure-dependent drainage in transgenic mice overexpressing endothelial NO synthase (eNOS) was studied. METHODS: IOP was measured by rebound tonometry in mice, and pressure versus flow data were measured by ex vivo perfusion at multiple pressures between 8 and 45 mm Hg, using mock AH ±100 μM L-NAME. A subset of eyes was examined histologically using standard techniques or was assayed for fusion protein expression by Western blot analysis. RESULTS: IOP was lower (9.6 ± 2.7 vs. 11.4 ± 2.5 mm Hg; mean ± SD; P = 0.04) and pressure-dependent drainage was higher (0.0154 ± 0.006 vs. 0.0066 ± 0.0009 μL/min/mm Hg; P = 0.002) in the transgenic mice than in the wild-type animals; however, pressure-independent drainage was unaffected. The NOS inhibitor L-NAME normalized pressure-dependent drainage in transgenic animals. For IOP >35 mm Hg, the slope of the pressure-flow curve in wild-type mice increased to match that seen in transgenic mice. Shear stress in the pressure-dependent pathway at elevated pressures was calculated to be in a range known to affect eNOS expression and activity in vascular endothelia. CONCLUSIONS: Endothelial NOS overexpression lowers IOP by increasing pressure-dependent drainage in the mouse eye. Data are consistent with NO's having a mechanoregulatory role in aqueous humor dynamics, with eNOS induction at elevated IOPs leading to increased pressure-dependent outflow. |
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Authors:
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W Daniel Stamer; Yuan Lei; Alexandra Boussommier-Calleja; Darryl R Overby; C Ross Ethier |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-09 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 52 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2011 |
Date Detail:
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Created Date: 2011-12-14 Completed Date: 2012-01-31 Revised Date: 2012-03-05 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 9438-44 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology and Vision Science, University of Arizona, Tucson, Arizona, USA. dan.stamer@duke.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aqueous Humor / physiology Blotting, Western DNA / genetics* Disease Models, Animal Endothelium, Corneal / enzymology*, pathology Gene Expression Regulation* Genotype Intraocular Pressure / physiology* Mice Mice, Inbred C57BL Nitric Oxide Synthase Type III / biosynthesis, genetics* Ocular Hypertension / enzymology, genetics*, physiopathology Polymerase Chain Reaction Tonometry, Ocular |
| Grant Support | |
ID/Acronym/Agency:
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EY17007/EY/NEI NIH HHS; EY19696/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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9007-49-2/DNA; EC 1.14.13.39/Nitric Oxide Synthase Type III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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