Abstract:
Purpose:The trabecular meshwork (TM) has an important role in the regulation of aqueous humor outflow and IOP. Regulation of the extracellular matrix (ECM) by TGFβ2 has been studied extensively. Bone morphogenetic protein (BMP) and activin membrane-bound inhibitor (BAMBI) has been shown to inhibit or modulate TGFβ2 signaling. We investigate the role of TGFβ2 and BAMBI in the regulation of TM ECM and ocular hypertension. Methods:Mouse TM (MTM) cells were isolated from B6;129S1-Bambitm1Jian/J flox mice, characterized for TGFβ2 and dexamethasone (DEX)-induced expression of fibronectin, collagen-1, collagen-4, laminin, α-smooth muscle actin, cross-linked actin networks (CLANs) formation, and DEX-induced myocilin (MYOC) expression. MTM cells were transduced with Ad5.GFP to identify transduction efficiency. MTM cells and mouse eyes were transduced with Ad5.Null, Ad5.Cre, Ad5.TGFβ2, or Ad5.TGFβ2 + Ad5.Cre to evaluate the effect on ECM production, IOP, and outflow facility. Results:MTM cells express TM markers and respond to DEX and TGFβ2. Ad5.GFP at 100 MOI had the highest transduction efficiency. Bambi knockdown by Ad5.Cre and Ad5.TGFβ2 increased fibronectin, collagen-1, and collagen-4 in TM cells in culture and tissue. Ad5.Cre, Ad5.TGFβ2, and Ad5.TGFβ2 + Ad5.Cre each significantly induced ocular hypertension and lowered aqueous humor outflow facility in transduced eyes. Conclusions:We show for the first time to our knowledge that knockdown of Bambi alters ECM expression in cultured cells and mouse TM, reduces outflow facility, and causes ocular hypertension. These data provide a novel insight into the development of glaucomatous TM damage and identify BAMBI as an important regulator of TM ECM and ocular hypertension.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Hernandez H,Millar JC,Curry SM,Clark AF,McDowell CMdoi
10.1167/iovs.17-23282subject
Has Abstractpub_date
2018-04-01 00:00:00pages
2154-2166issue
5eissn
0146-0404issn
1552-5783pii
2679805journal_volume
59pub_type
杂志文章abstract:Purpose:High myopia (HM) is defined as a refractive error worse than -6.00 diopter (D). This study aims to update the phenotypic and genotypic landscape of nonsyndromic HM and to establish a biological link between the phenotypic traits and genetic deficiencies. Methods:A cross-sectional study involving 731 participan...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.19-27921
更新日期:2019-09-03 00:00:00
abstract::An animal model has been developed to study the effects of various prophylaxis agents on acquisition of chlamydial conjunctivitis. When Hartley strain newborn guinea pigs received ocular inoculations of Chlamydia psittaci followed by the instillation of various agents, 1% AgNO3 significantly lowered the risk of develo...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0226
更新日期:2007-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2017-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2009-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2015-01-08 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2016-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
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更新日期:2006-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:10.1167/iovs.15-18035
更新日期:2015-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:10.1167/iovs.16-20243
更新日期:2016-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-23627
更新日期:2018-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4748
更新日期:2011-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
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journal_title:Investigative ophthalmology & visual science
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更新日期:2001-11-01 00:00:00
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更新日期:2007-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2003-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1980-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2011-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1977-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2013-05-07 00:00:00
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pub_type: 杂志文章
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更新日期:2007-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章
doi:
更新日期:2000-09-01 00:00:00