Abstract:
PURPOSE:Excitotoxicity has been proposed to play a pivotal role in retinal damage, but the mechanisms that underlie retinal damage are not clearly understood. In this study, the role of matrix metalloproteinases in excitotoxin-mediated retinal damage was investigated. METHODS:KA, CNQX (6-cyano-7-nitroquinoxaline-2,3,-dione), NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline), MK801, or PBS was injected into the vitreous of CD-1 mice. MMP expression in the retina was analyzed by zymography, Western blot, and immunohistochemistry. Retinal ganglion cells (RGCs) were retrogradely labeled with aminostilbamidine methanesulfonate (Molecular Probes, Eugene, OR), and loss of fluorescently labeled RGCs in retinal flatmounts was quantified. Apoptotic cell death was assessed by TUNEL staining. Astrocyte activation was determined by immunohistochemistry, and laminin decrease was determined by immunohistochemistry and Western blot analysis. RESULTS:Intravitreal injection of KA caused time- and dose-related MMP-9 upregulation in the retina. Increased MMP-9 activity and protein levels were associated with activation of astrocytes. Astrocyte-associated MMP-9 correlated with a decrease in laminin immunoreactivity in the ganglion cell layer and significant loss of retinal ganglion cells. KA-mediated upregulation of MMP-9 activity was associated with apoptosis of cells in the ganglion cell layer as early as 6 hours after injection, followed by apoptosis in cells in the inner nuclear layer by day 1. Intravitreal injection of the non-NMDA receptor antagonists, CNQX and NBQX decreased KA-induced MMP-9 activity and protein levels in the retina and attenuated retinal degeneration, whereas the NMDA receptor antagonist MK801 failed to offer protection. Further, a synthetic MMP inhibitor GM6001 decreased KA-mediated MMP-9 activity and offered significant protection against ganglion cell loss in the retina. CONCLUSIONS:These results indicate that KA-mediated upregulation of MMP-9 activity promotes retinal degeneration and suggest that inhibition of KA-mediated MMP activity may offer protection against excitotoxin-induced retinal damage.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Zhang X,Cheng M,Chintala SKdoi
10.1167/iovs.03-1239keywords:
subject
Has Abstractpub_date
2004-07-01 00:00:00pages
2374-83issue
7eissn
0146-0404issn
1552-5783journal_volume
45pub_type
杂志文章abstract:PURPOSE:Because immune rejection is likely to be a major barrier to successful retinal transplantation, it is important to determine whether immune privilege for allogeneic retinal grafts is a feature of the subretinal space and vitreous cavity. METHODS:Newborn neural retinas of C57BL/6 mice were implanted into the su...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::Fixation stability of the saccadic system was investigated by infrared reflection oculography in 29 normal subjects, young and elderly. Square wave jerks consisting of spontaneous horizontal saccadic excursions of 0.5 degree and over, followed some 200 msec later by corrective saccades, were recorded in 24% of subject...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1981-02-01 00:00:00
abstract:PURPOSE:The virulence of any given strain of herpes simplex virus (HSV) is probably due to the effects of the constellation of genes in that strain and how they act in concert to promote disease. The goal of this work was to develop a system to identify and study the role of multiple genes in HSV disease. METHODS:Mixe...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-1105
更新日期:2003-06-01 00:00:00
abstract:PURPOSE:Macular corneal dystrophy (MCD) is a rare corneal dystrophy that is characterized by abnormal deposits in the corneal stroma, keratocytes, Descemet's membrane, and endothelium, accompanied by progressive clouding. It has been classified into three immunophenotypes--MCD types I, IA, and II--according to the seru...
journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:2002-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.01-1096
更新日期:2003-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12588
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.06-1309
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abstract:PURPOSE:The authors investigated whether trigeminal sensitization occurs in response to bright light with the retina disconnected from the rest of the central nervous system by optic nerve section. METHODS:In urethane-anesthetized rats, trigeminal reflex blinks were evoked with air puff stimuli directed at the cornea ...
journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.11-7604
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.12-10175
更新日期:2012-09-25 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2018-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-14439
更新日期:2014-10-14 00:00:00
abstract:UNLABELLED:PURPOSE. Test the hypothesis that the developmental increases in rod photoreceptor sensitivity and rod-mediated visual sensitivity at 10 degrees, 20 degrees , and 30 degrees eccentric are concurrent. It is known that maturation of the parafoveal (10 degrees eccentric) rod outer segments and visual sensitivit...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract:PURPOSE:To compare the developmental sequences of two basic measures of pattern vision, Vernier acuity and grating acuity, using steady state visual-evoked potentials (VEPs) and an analysis designed to isolate pattern-specific responses from those due to motion in the Vernier stimulus. METHODS:The authors recorded VEP...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract:PURPOSE:There are two human 15-lipoxygenases (LOX), 15-LOX-1 and -2, which convert arachidonic acid to 15S-hydroxyeicosatetraenoic acid (15S-HETE). The presence of both 15-LOXs in the human cornea prompted this study to delineate their roles in the human corneal epithelium. METHODS:Human corneal epithelia from donor c...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-1166
更新日期:2005-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0070
更新日期:2004-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.06-0861
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0452
更新日期:2007-05-01 00:00:00
abstract::Electroretinographic studies of myctalopic Appaloosa horses demonstrated photopic and scotopic abnormalities similar to those in humans with congenital stationary night blindness (CSNB) of the Schubert-Bornschein type. The phototopic abnormalities consisted of reduced b-wave amplitudes and slower than normal b-wave im...
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:10.1167/iovs.14-15067
更新日期:2014-09-09 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::In order to investigate the effect of traction of the vasculature on induction or acceleration of neovascularization, the chorioallantoic membranes (CAMs) of the developing chick embryo were placed under tension with 10-0 nylon sutures and subsequently examined histologically. In the initial phase of the study, CAMs f...
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
pub_type: 杂志文章
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更新日期:2018-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2009-04-01 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:2004-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2007-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2018-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2019-02-01 00:00:00
abstract::Docosapentaenoic acid (22:5 omega 6), a minor constituent (less than 4%) of photoreceptor outer segment membranes in all vertebrate species examined to date, comprises 23% of the fatty acids in total lipids from rabbit outer segment membranes. This fatty acid is a significant constituent of each of the three major pho...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1986-02-01 00:00:00
abstract:PURPOSE:Genetic modification of cells before transplantation may allow the delivery of neuroprotective and other functional molecules to patients with neurodegenerative diseases. To avoid complications associated with virally transfected cells, we have explored the use of nonviral methods to insert genetic material int...
journal_title:Investigative ophthalmology & visual science
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更新日期:2011-07-23 00:00:00