Abstract:
PURPOSE:To assess the neuroprotective effects of different glutamate modulation strategies, with a nonselective (MK801) and a selective (ifenprodil) NMDA receptor antagonist and a metabotropic glutamate receptor agonist (mGluR Group II, LY354740), in glaucoma-related in vivo rat models of retinal ganglion cell (RGC) apoptosis. METHODS:RGC apoptosis was induced in Dark Agouti (DA) rats by staurosporine (SSP) treatment. Single agents MK801, ifenprodil, or LY354740, or MK801 and LY354740 combined, were administrated intravitreally at different doses. Eyes were imaged in vivo using a recently established technique and the results confirmed histologically. The most effective combined therapy regimen of MK801 and LY354740 was then assessed in a chronic ocular hypertension (OHT) rat model with application at 0, 1, and 2 weeks after OHT surgery and the effects assessed as described before. RESULTS:All strategies of glutamate modulation reduced SSP-induced-RGC apoptosis compared with the control, in a dose-dependent manner: MK801 (R2= 0.8863), ifenprodil (R2= 0.4587), and LY354740 (R2= 0.9094), with EC50s of 0.074, 0.0138, and 19 nanomoles, respectively. The most effective combination dose of MK801 and LY354740 was 0.06 and 20 nanomoles (P < 0.05), respectively, and the optimal timing of the therapy was 0 weeks after OHT surgery (P < 0.05). CONCLUSIONS:This novel SSP model was validated as a useful tool for screening neuroprotective strategies in vivo. Group II mGluR modulation may be a useful treatment for RGC death. Combination therapy optimized to limit neurotoxic effects of MK801 may be an effective neuroprotective approach in retinal degenerative disease. Furthermore, treatments that minimize secondary RGC degeneration may be most useful in glaucoma.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Guo L,Salt TE,Maass A,Luong V,Moss SE,Fitzke FW,Cordeiro MFdoi
10.1167/iovs.05-0754keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
626-33issue
2eissn
0146-0404issn
1552-5783pii
47/2/626journal_volume
47pub_type
杂志文章abstract:PURPOSE:To assess cross-sectional and longitudinal associations between exposure to Chlamydia pneumoniae infection and age-related macular degeneration (AMD) in the nested case-control sample drawn from the Blue Mountains Eye Study (BMES) cohort. METHODS:The BMES examined 3654 persons aged 49 to 97 years during 1992 t...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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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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abstract:PURPOSE:To determine the response of retinal vessels to differing durations of flicker light (FL) stimulation. METHODS:We recorded retinal arterial and venous vessel dilation to 12.5 Hz FL provocation of varying duration (5, 7, 10, and 20 seconds) in 12 healthy young individuals (age range, 26-45 years). All participa...
journal_title:Investigative ophthalmology & visual science
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abstract:PURPOSE:A prior study showed that Toll-like receptor (TLR)-5 recognizes Pseudomonas aeruginosa flagellin and triggers the production of proinflammatory cytokines in human corneal epithelial cells (HCECs). The present study was conducted to determine how the inflammatory response is modulated after TLR activation in HCE...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0473
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract:PURPOSE:The purpose of this study was to evaluate expression of methyl-CpG-binding protein 2 (MeCP2) in epiretinal membranes from patients with proliferative vitreoretinopathy (PVR) and to investigate effects of inhibition of MeCP2 and DNA methylation on transforming growth factor (TGF)-β-induced retinal pigment epithe...
journal_title:Investigative ophthalmology & visual science
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abstract::Analysis of cell populations in the cornea may be performed rapidly and accurately employing the technique of enzymatic disaggregation. To illustrate this method normal rat corneas and corneas infected 24 and 48 hours previously with Staphylococcus aureus were disaggregated in a solution containing pancreatin and coll...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-02-01 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: 临床试验,杂志文章,随机对照试验
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更新日期:1996-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1999-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
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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
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更新日期:2002-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2011-12-09 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1984-08-01 00:00:00
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更新日期:2007-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1988-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1999-12-01 00:00:00
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更新日期:2013-06-04 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00