Abstract:
PURPOSE:Compelling evidence suggests that alpha2 agonists, such as brimonidine, protect retinal ganglion cells (RGCs) from injury in a wide range of animal models. However, the mechanism of action for this protection and the physiological role of the alpha2 adrenergic system in the retina is not well understood. A major goal of this work was to explore the role of the alpha2 adrenergic system in the modulation of cytosolic Ca(2+) signaling at retinal synaptic layers, particularly the inner plexiform layer (IPL), where communication between RGCs and their presynaptic cells takes place. METHODS:Functional Ca(2+) imaging at the inner plexiform layer (IPL) and outer plexiform layer (OPL) of living rat retinal slices was conducted with a high-speed confocal system. The relative changes of cytosolic free Ca(2+) were monitored with the fluorescent Ca(2+) dye fluo-4. The Ca(2+) signal was elicited by membrane depolarization produced by a high K(+) (40 mM) Ringer solution that was delivered rapidly and briefly to the test regions of the retinal slice by a custom-made multichannel local perfusion system. RESULTS:A brief application (8 seconds) of high K(+) Ringer elicited a robust cytosolic Ca(2+) increase at the IPL and OPL. In both cases, this Ca(2+) signal was eliminated by nimodipine, a selective L-type voltage-gated Ca(2+)-channel blocker, or when the extracellular Ca(2+) in the Ringer was replaced with equal molar EGTA. At IPL, the Ca(2+) signal was also suppressed in a dose-dependent manner by brimonidine and other alpha2 receptor agonists, such as medetomidine. The suppressive action of brimonidine and medetomidine was completely blocked by classic alpha2 receptor antagonists, such as yohimbine, rauwolscine, and atipamezole. Interestingly, the alpha2 receptor agonists had no effect on the high K(+) Ringer-elicited cytosolic Ca(2+) signal at OPL. Blocking the N-methyl-d-aspartate (NMDA) type of ionotropic glutamate receptor with D-AP5 attenuated this high K(+)-elicited Ca(2+) signal by approximately 20% at IPL. D-AP5 had no effect on the Ca(2+) signal at OPL. CONCLUSIONS:These findings provide the first direct evidence of alpha2 receptor-mediated modulation of L-type Ca(2+) channel activity in the CNS (the retina is part of the CNS). This alpha2 modulation appears to occur at the IPL but not at the OPL of the retina. These findings suggest that a physiological function of the retinal alpha2 system is the regulation of synaptic transmission at IPL and that brimonidine and other alpha2 agonists may protect RGCs under disease conditions by preventing abnormal elevation of cytosolic free Ca(2+) either in RGCs, in their presynaptic cells, or in both.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Dong CJ,Guo Y,Wheeler L,Hare WAdoi
10.1167/iovs.06-0890subject
Has Abstractpub_date
2007-03-01 00:00:00pages
1410-5issue
3eissn
0146-0404issn
1552-5783pii
48/3/1410journal_volume
48pub_type
杂志文章abstract:PURPOSE:MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal gland inflammatory lesions and are a model for the human disease Sjögren's syndrome. Therapy with monoclonal antibodies (mAb) to CD4 ameliorates the autoimmune renal, vasculitic, and intraocular inflammatory lesions in MRL/lpr mice. The effect of anti...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:We examined the treatment period necessary to restore retinal and visual stability following trauma to the optic nerve. METHODS:Cats received unilateral optic nerve crush and no treatment (NT), treatment of the injured eye with brain-derived neurotrophic factor (BDNF), or treatment of the injured eye combined ...
journal_title:Investigative ophthalmology & visual science
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abstract:PURPOSE:Although the murine alphaA-crystallin promoter is the most commonly used promoter for achieving transgene expression in the developing lens, this promoter directs transgene expression efficiently only in lens fiber cells. The purpose of the present study was to generate promoters capable of directing transgene ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0856
更新日期:2004-06-01 00:00:00
abstract:Purpose:Thymic stromal lymphopoietin (TSLP) is a pro-allergic cytokine that initiates allergic inflammatory reaction between epithelial and dendritic cells (DCs). miR-19b was reported to suppress TSLP expression. The present study aimed to examine miR-19b expression, regulation, and function in allergic conjunctivitis ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.3.8
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abstract:PURPOSE:To test whether triamcinolone acetonide (TA) inhibits angiogenesis induced by IL-6 or VEGF and whether this inhibition is through antagonism of the IL-6 or the VEGF receptor 2. METHODS:A rat cornea micropocket assay was used to initiate IL-6- and VEGF-mediated angiogenesis. The ability of TA or neutralizing VE...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1651
更新日期:2006-11-01 00:00:00
abstract::Previous studies have shown that aqueous humor of calf and human eyes contains about 25 microM hydrogen peroxide. We have studied the removal of hydrogen peroxide by the outflow pathway of intact, freshly enucleated, calf eyes. Eyes were immersed under silicone oil that had a density greater than water and medium cont...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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journal_title:Investigative ophthalmology & visual science
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更新日期:2013-09-19 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:2013-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2013-10-03 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:
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journal_title:Investigative ophthalmology & visual science
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更新日期:2020-06-03 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.10-7055
更新日期:2011-07-15 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract:PURPOSE:To investigate phenotype characteristics of fellow eyes in patients with early onset of neovascular age-related macular degeneration (NVAMD). METHODS:Patients with new-onset unilateral NVAMD between 50 and 65 years (n = 57, early-onset choroidal neovascularization [CNV] group) or >80 years (n = 47, late-onset ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-16989
更新日期:2015-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Membrane-bound proteins in plasma membrane enriched fractions from cultured rat RPE were analyzed by two-dimensional gel electrophoresis. Membrane proteins were characterized on three increasingly specific levels. Total protein was visualized by silver staining. A maximum of 102 separate proteins were counted in silve...
journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1986-02-01 00:00:00
abstract:PURPOSE:Clonidine and brimonidine, two alpha-2 agonists, have been shown to reduce intraocular pressure (IOP) in patients with glaucoma. Little is known, however, about the exact role of alpha receptors in the control of ocular blood flow in the posterior pole of the eye. Hence, the study was conducted to investigate t...
journal_title:Investigative ophthalmology & visual science
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更新日期:2007-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2008-11-01 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
abstract:Purpose:To determine age-related alterations in the retinal tissue perfusion (RTP) and volumetric vessel density (VVD) in healthy subjects. Methods:Total 148 healthy subjects (age 18 to 83 years) were enrolled and divided into four groups (G1, <35 years; G2, 35 ∼ 49 years; G3, 50 ∼ 64 years; and G4, ≥65 years). The RT...
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更新日期:2019-02-01 00:00:00
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doi:10.1167/iovs.05-0039
更新日期:2005-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.08-2634
更新日期:2009-08-01 00:00:00
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doi:10.1167/iovs.61.14.34
更新日期:2020-12-01 00:00:00
abstract::The acute effect of topical epinephrine HCl 2% on macular capillary blood flow was studied in 18 healthy human volunteers using the blue-field simulation technique. This technique provides a method for quantifying the velocity of leukocytes flowing in macular capillaries. Subjects adjusted the velocity of simulated le...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:To investigate whether time outdoors and a range of other activities are associated with change in spherical equivalent (SE) and axial length in Chinese children over a period of 2 years. METHODS:A total of 1997 children aged 12.7 ± 0.5 (10.9-15.6) years in the Anyang Childhood Eye Study (ACES) were examined a...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2015-07-01 00:00:00
abstract:PURPOSE:To determine and compare gene expression patterns in the whole retina and retinal ganglion cell layer (RGCL) in a rodent glaucoma model. METHODS:IOP was unilaterally elevated in Brown Norway rats (N = 26) by injection of hypertonic saline and monitored for 5 weeks. A cDNA microarray was used on whole retinas f...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4663
更新日期:2010-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00