Journal article
Caveolin-1 modulates intraocular pressure: implications for caveolae mechanoprotection in glaucoma
Scientific reports, Vol.6(1), pp.37127-37127
11/14/2016
DOI: 10.1038/srep37127
PMCID: PMC5107904
PMID: 27841369
Abstract
Polymorphisms in the CAV1/2 genes that encode signature proteins of caveolae are associated with glaucoma, the second leading cause of blindness worldwide, and with its major risk factor, intraocular pressure (IOP). We hypothesized that caveolin-1 (Cav-1) participates in IOP maintenance via modulation of aqueous humor drainage from the eye. We localize caveolae proteins to human and murine conventional drainage tissues and show that caveolae respond to mechanical stimulation. We show that Cav-1-deficient (Cav-1
) mice display ocular hypertension explained by reduced pressure-dependent drainage of aqueous humor. Cav-1 deficiency results in loss of caveolae in the Schlemm's canal (SC) and trabecular meshwork. However, their absence did not appear to impact development nor adult form of the conventional outflow tissues according to rigorous quantitative ultrastructural analyses, but did affect cell and tissue behavior. Thus, when IOP is experimentally elevated, cells of the Cav-1
outflow tissues are more susceptible to plasma membrane rupture indicating that caveolae play a role in mechanoprotection. Additionally, aqueous drainage from Cav-1
eyes was more sensitive to nitric oxide (NO) synthase inhibition than controls, suggesting that excess NO partially compensates for outflow pathway dysfunction. These results provide a functional link between a glaucoma risk gene and glaucoma-relevant pathophysiology.
Details
- Title: Subtitle
- Caveolin-1 modulates intraocular pressure: implications for caveolae mechanoprotection in glaucoma
- Creators
- Michael H Elliott - Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, OK, USANicole E Ashpole - Department of Ophthalmology/Duke Eye Center, Duke University, Durham, 27710, NC, USAXiaowu Gu - Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, OK, USALeonie Herrnberger - Institute of Human Anatomy and Embryology, Universität Regensburg, 93053 Regensburg, GermanyMark E McClellan - Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, OK, USAGina L Griffith - Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, OK, USAAlaina M Reagan - Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, OK, USATimothy M Boyce - Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, OK, USAMasaki Tanito - Division of Ophthalmology, Matsue Red Cross Hospital, Matsue, Shimane 690-8506 JapanErnst R Tamm - Institute of Human Anatomy and Embryology, Universität Regensburg, 93053 Regensburg, GermanyW Daniel Stamer - Department of Ophthalmology/Duke Eye Center, Duke University, Durham, 27710, NC, USA
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.6(1), pp.37127-37127
- DOI
- 10.1038/srep37127
- PMID
- 27841369
- PMCID
- PMC5107904
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Grant note
- P30 EY021725 / NEI NIH HHS R01 EY022359 / NEI NIH HHS R01 EY019494 / NEI NIH HHS T32 EY023202 / NEI NIH HHS P30 EY005722 / NEI NIH HHS
- Language
- English
- Date published
- 11/14/2016
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9984172168402771
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