Abstract:
PURPOSE:In corneal endothelial cells, intercellular Ca(2+) waves elicited by a mechanical stimulus involve paracrine intercellular communication, mediated by ATP release via connexin hemichannels, as well as gap junctional intercellular communication. Both mechanisms are inhibited by thrombin, which activates RhoA and hence results in myosin light chain phosphorylation. This study was conducted to examine the effects of adenosine, which is known to oppose thrombin-induced RhoA activation, thereby leading to myosin light chain dephosphorylation, on gap junctional intercellular communication and paracrine intercellular communication in cultured bovine corneal endothelial cells. METHODS:An intercellular Ca(2+) wave was elicited by applying a mechanical stimulus to a single cell in a confluent monolayer. The area of Ca(2+) wave propagation was measured by [Ca(2+)](i) imaging using the fluorescent dye Fluo-4. Gap junctional intercellular communication was assessed by fluorescence recovery after photobleaching. Activity of hemichannels was determined by uptake of the hydrophilic dye Lucifer yellow in a Ca(2+)-free medium containing 2 mM EGTA. Adenosine triphosphate (ATP) release in response to mechanical stimulation was measured using the luciferin-luciferase technique. Gap26, a connexin mimetic peptide, was used to block hemichannels. RESULTS:Exposure to thrombin or TRAP-6 (a selective PAR-1 agonist) inhibited the Ca(2+) wave propagation by 70%. Pretreatment with adenosine prevented this inhibitory effect of thrombin. NECA (a potent A2B agonist) and forskolin, agents known to elevate cAMP in bovine corneal endothelial cells, also suppressed the effect of thrombin. The A1 receptor agonist CPA failed to inhibit the effect of thrombin. Similar to the effects on Ca(2+) wave propagation, adenosine prevented the thrombin-induced reduction in the fluorescence recovery during photobleaching experiments. Furthermore, pretreatment with adenosine prevented both thrombin and TRAP-6 from blocking the uptake of Lucifer yellow in a Ca(2+)-free medium. However, adenosine was ineffective in overcoming the Gap26-mediated block of Lucifer yellow uptake. In consistence with Lucifer yellow uptake through hemichannels, the thrombin-induced inhibition of ATP release was overcome by pretreatment with adenosine. CONCLUSIONS:Adenosine prevents thrombin-induced inhibition of hemichannel-mediated paracrine intercellular communication and of gap junctional intercellular communication. The mechanism involves an increase in cAMP, which results in inhibition of RhoA and a subsequent decrease in myosin light chain phosphorylation. Since myosin light chain dephosphorylation causes a decrease in contractility of the actin cytoskeleton, the results suggest possible effects of the actin cytoskeleton on gap junctions and connexin hemichannels.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
D'hondt C,Srinivas SP,Vereecke J,Himpens Bdoi
10.1167/iovs.06-1062subject
Has Abstractpub_date
2007-04-01 00:00:00pages
1518-27issue
4eissn
0146-0404issn
1552-5783pii
48/4/1518journal_volume
48pub_type
杂志文章abstract:PURPOSE:Using transient ischemia followed by reperfusion (IR) to model ischemic retinal disease, this study compares the effects of ischemic preconditioning (IPC) and therapies targeting vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α on retinal apoptosis, vascular permeability, and mRNA exp...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5264
更新日期:2010-11-01 00:00:00
abstract:Purpose:To investigate factors associated with visual field (VF) progression in treated myopic normal-tension glaucoma (NTG) using a novel posterior sclera reconstruction method involving swept-source optical coherence tomography (OCT). Methods:Fifty-six myopic patients on ocular hypotensive therapy with the diagnose ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.19-26794
更新日期:2019-05-01 00:00:00
abstract:PURPOSE:To examine the prognostic relevance of expression of the chemokine receptors CCR7 and CXCR4 and its ligand CXCL12 in uveal melanoma in nonmetastatic and metastatic patients with correlation to liver metastasis and overall survival. METHODS:Primary uveal melanoma specimens from 19 patients with correlating live...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12407
更新日期:2013-11-08 00:00:00
abstract:PURPOSE:To identify the disease locus associated with autosomal dominant Fuchs corneal dystrophy (FCD) in a large family and to compare the progression of severity in families mapped to the FCD1 and FCD2 loci. METHODS:Seventeen individuals in a large family were examined by slit lamp biomicroscopy. Blood samples were ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-3764
更新日期:2009-12-01 00:00:00
abstract:PURPOSE:The present study was undertaken to examine the relationship between choroidal permeability and scleral glycosaminoglycan synthesis rates during the development of and recovery from form deprivation myopia. METHODS:Form deprivation myopia was induced in chicks for 10 days and was followed by a period of unrest...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-1051
更新日期:2007-07-01 00:00:00
abstract:PURPOSE:To determine the accommodative accuracy of infants and young children before they had had any form of clinical intervention or treatment, in an attempt to determine the difference between 'normal' and 'abnormal' visual experience for these individuals. METHODS:Nott retinoscopy was performed on 111 subjects in ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8174
更新日期:2012-01-17 00:00:00
abstract:PURPOSE:The authors recently reported that a severe inflammatory response resulting in substantial loss of acinar cells was induced by a single injection of interleukin-1alpha into the lacrimal gland and that this effect was reversible. The purpose of the present study was to determine the mechanisms involved in lacrim...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-1730
更新日期:2008-10-01 00:00:00
abstract:PURPOSE:To describe the cross-sectional relationship between retinal arteriolar and venular diameters with age and blood pressure. METHODS:A population-based study was conducted in Beaver Dam, Wisconsin (n=4926, age range, 43-84 years). Retinal photographs of right eyes taken at the baseline examination (1988-90) were...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0079
更新日期:2003-11-01 00:00:00
abstract:PURPOSE:To investigate macular photoreceptor structure in patients with inherited retinal degeneration using high-resolution images and to correlate the findings with clinical phenotypes and genetic mutations. METHODS:Adaptive optics scanning laser ophthalmoscopy (AOSLO) images of photoreceptors were obtained in 16 ey...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-1422
更新日期:2007-07-01 00:00:00
abstract:PURPOSE:Previous work from the authors' laboratory has shown that Hsp27 is specifically upregulated after retinal ischemic preconditioning (IPC), and this upregulation acts as a key cytoprotective factor in preventing retinal ischemic damage. The regulatory mechanisms involved in the upregulation of Hsp27 after IPC are...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0043
更新日期:2005-03-01 00:00:00
abstract:PURPOSE:To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head. METHODS:This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (C...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-13657
更新日期:2014-04-15 00:00:00
abstract:PURPOSE:To assess the reproducibility of the ocular response analyzer (ORA) in nonoperated eyes and the impact of corneal biomechanical properties on intraocular pressure (IOP) measurements in normal and glaucomatous eyes. METHODS:In the reliability study, two independent examiners obtained repeated ORA measurements i...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0280
更新日期:2008-03-01 00:00:00
abstract:PURPOSE:To investigate the prevalence and characteristics of primary angle-closure suspect (PACS), primary angle closure (PAC), and primary angle-closure glaucoma (PACG) in a rural population in China. METHODS:In all, 6716 Han Chinese 30 years of age and older (5480 subjects 40 years of age and older) from 13 villages...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-7480
更新日期:2011-11-07 00:00:00
abstract:PURPOSE:Endotoxin-induced uveitis (EIU) is a model that mimics human acute anterior uveitis. Cyclooxygenase (COX)-2 is an enzyme that initiates the conversion of arachidonic acid (AA) into prostaglandins (PGs), whereas 5-lipoxygenase (5-LO) generates leukotrienes (LT). The purpose of this study was to delineate the rol...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0756
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:To determine the effect of human recombinant TIGR/myocilin (MYOC) protein on outflow resistance in the human anterior segment. METHODS:A cDNA for MYOC was inserted into a bacterial expression system and purified with nickel ion affinity chromatography. The anterior segments of 12 pairs of human eyes were place...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract:PURPOSE:The transplantation of cultivated corneal endothelial cells (CECs) has gained attention recently for the treatment of patients with corneal endothelial dysfunction. However, an efficient culturing technique for human (H)CECs has yet to be properly established. The present study was conducted to investigate the ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-2634
更新日期:2009-08-01 00:00:00
abstract:PURPOSE:To investigate the role of the gap junction protein connexin43 (Cx43), which is predominantly expressed in lens epithelial cells in the control of lens development and organization. METHODS:Newborn mice in which the Cx43 gene was disrupted by homologous recombination were used. Lenses from Cx43 (-/-) mice and ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract:PURPOSE:To investigate whether signaling pathways that incorporate protein tyrosine kinases and phosphatases regulate PKC-sensitive, volume-sensitive Cl(-) currents (I(Cl,vol)) in cultured rabbit nonpigmented ciliary epithelial cells. METHODS:Activation of I(Cl,vol) in response to hyposmotic stimulation was recorded w...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
abstract:PURPOSE:To examine the relationship between short-wavelength-sensitive (SWS) resolution acuity and epidemiologically defined stages of early age-related maculopathy (ARM). METHODS:Subjects consisted of 88 adults aged 51 to 87 years. Psychophysical testing was undertaken in only one eye of each subject (the study eye)....
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1227
更新日期:2006-10-01 00:00:00
abstract:PURPOSE:To investigate the effect of ABCA4 mutation status on lipofuscin-related quantitative autofluorescence (qAF) in humans and on bisretinoid accumulation in mice. METHODS:Genotyped parents (n = 26; age 37-64 years) of patients with biallelic ABCA4-related retinopathy underwent in-depth retinal phenotyping includi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-17629
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:Evidence suggests that capillary degeneration in early diabetic retinopathy results from chronic inflammation, and leukotrienes have been implicated in this process. The authors investigated the cellular sources of leukotriene biosynthesis in diabetic retinas and the effects of hyperglycemia on leukotriene prod...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-3557
更新日期:2010-03-01 00:00:00
abstract:PURPOSE:In Program K, a new automated kinetic algorithm that we developed, the frequency distributions of the number of patients' response points were obtained for external angles to distinguish normal and abnormal isopters. We also assessed the agreement between the results of Program K and Goldmann manual kinetic per...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-16182
更新日期:2015-03-05 00:00:00
abstract:Purpose:To employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD). Methods:The qAF imaging was performed on eyes of 26 rhesus macaques (me...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.8.16
更新日期:2020-07-01 00:00:00
abstract:PURPOSE:To determine the effects of silencing Toll-like receptor (TLR) 9 signaling in Pseudomonas aeruginosa keratitis. METHODS:Corneal TLR9 mRNA levels were tested by RT-PCR in C57BL/6 (B6, susceptible) and BALB/c (resistant) mice and compared. The response of B6 mice to CpG DNA, which binds TLR9, was tested after su...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0185
更新日期:2005-11-01 00:00:00
abstract::Checkerboard reversal stimuli were used to evoke transient pattern electroretinograms (P-ERGs) from the eyes of 14 patients with amblyopia and 14 normal subjects. In the control group, and in normal eyes of patients, pattern electroretinograms were obtained with monocular central fixation. Amblyopic eyes were examined...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:Peripheral and limbal corneal stromal cells (PLCSCs), which contain keratocytes, have a complex phenotype. Knowledge of keratocyte cell properties, function, and origin is limited. Evidence available thus far has suggested both mesenchymal stromal and hematopoietic characteristics. Multipotent mesenchymal strom...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8673
更新日期:2012-08-03 00:00:00
abstract:PURPOSE:To characterize the spectrum of mutations in the OPA1 gene in a large international panel of patients with autosomal dominant optic atrophy (adOA), to improve understanding of the range of functional deficits attributable to sequence variants in this gene, and to assess any genotype-phenotype correlations. MET...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:
更新日期:2002-06-01 00:00:00
abstract:PURPOSE:In the rabbit iris sphincter muscle, sodium nitroprusside (SNP), a nitric oxide (NO) donor, inhibits cholinergic contraction but does not affect tachykinergic contraction in vitro. The objectives of the current study were to clarify the mechanism for the different responsiveness to NO in cholinergic and tachyki...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::Assays of cortisol-metabolizing enzymes in homogenates of human trabecular meshwork cells under optimal conditions revealed two defects in primary open-angle glaucoma (POAG): one is a marked increase in delta 4-reductase and the other is a decrease in 3-oxidoreductase. Experiments indicated that the differences in enz...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1985-06-01 00:00:00
abstract:PURPOSE:To examine the effects of transcorneal electrical stimulation (TES) on retinal degeneration of light-exposed rats. METHODS:Thirty-three Sprague Dawley albino rats were divided into three groups: STIM (n = 15) received 60 minutes of TES, whereas SHAM (n = 15) received identical sham stimulation 2 hours before e...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-10037
更新日期:2012-08-15 00:00:00