Abstract:
Purpose:To determine whether high glucose (HG) or diabetes alters mitochondrial morphology and promotes mitochondrial fragmentation in retinal vascular cells and thereby triggers apoptosis associated with diabetic retinopathy. Methods:To assess whether diabetes promotes mitochondrial fragmentation and thereby triggers apoptosis, retinas from nondiabetic and diabetic rats were analyzed using electron microscopy (EM) and in parallel, wild-type, diabetic, and OPA1+/- mice were analyzed for optic atrophy gene 1 (OPA1) and cytochrome c levels using Western blot (WB) analysis. To assess the relationship between mitochondrial fragmentation and OPA1 levels, rat retinal endothelial cells (RRECs) were grown in normal (N; 5 mmol/L) medium, HG (30 mmol/L) medium, or in N medium transfected with OPA1 siRNA for seven days. Cells were examined for OPA1 expression and cytochrome c release by WB. In parallel, cells were stained with MitoTracker Red and assessed for mitochondrial fragmentation in live cells using confocal microscopy. Results:EM images revealed significant mitochondrial fragmentation in vascular cells of retinal capillaries of diabetic rats compared with that of nondiabetic rats. WB analysis showed significant OPA1 downregulation concomitant with increased levels of proapoptotic cytochrome c levels in cells grown in HG and in cells transfected with OPA1 siRNA alone. Similarly, OPA1 level was significantly reduced in diabetic retinas compared with that of nondiabetic retinas. Interestingly, OPA1+/- animals exhibited elevated cytochrome c release similar to those of diabetic mice. Conclusions:Findings indicate that diabetes promotes mitochondrial fragmentation in retinal vascular cells, which are driven, at least in part, by decreased OPA1 levels leading to apoptosis in diabetic retinopathy.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Kim D,Roy Sdoi
10.1167/iovs.61.10.10subject
Has Abstractpub_date
2020-08-03 00:00:00pages
10issue
10eissn
0146-0404issn
1552-5783pii
2770577journal_volume
61pub_type
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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更新日期:2007-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0422
更新日期:2006-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1978-08-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.05-0234
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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:1984-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1998-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2019-09-03 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0834
更新日期:2007-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract:PURPOSE:To assess the repeatability and interoperator and intersession reproducibility of central corneal thickness (CCT) measurements made by a commercially available optical coherence tomography (OCT) system. METHODS:Intersession and interoperator reproducibility and repeatability were defined according to the guide...
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pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1994-02-01 00:00:00
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更新日期:2011-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2006-06-01 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:2012-04-18 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-03-01 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:2011-10-11 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2015-08-01 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:2010-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1229
更新日期:2006-07-01 00:00:00