Abstract:
:PURPOSE. To define the role of the serine protease HTRA1 in age-related macular degeneration (AMD) by examining its expression level and identifying its potential substrates in the context of primary RPE cell extracellular milieu. METHODS. Primary RPE cell cultures were established from human donor eyes and screened for CFH, ARMS2, and HTRA1 risk genotypes by using an allele-discrimination assay. HTRA1 expression in genotyped RPE cells was determined by using real-time PCR and quantitative proteomics. Potential HTRA1 substrates were identified by incubating RPE-conditioned medium with or without human recombinant HTRA1. Selectively cleaved proteins were quantified by using the differential stable isotope labeling by amino acids in cell culture (SILAC) strategy. RESULTS. HTRA1 mRNA levels were threefold higher in primary RPE cells homozygous for the HTRA1 promoter risk allele than in RPE cells with the wild-type allele, which translated into a twofold increase in HTRA1 secretion by RPE cells with the risk genotype. A total of 196 extracellular proteins were identified in the RPE secretome, and only 8 were found to be selectively cleaved by the human recombinant HTRA1. These include fibromodulin with 90% cleavage, clusterin (50%), ADAM9 (54%), vitronectin (54%), and alpha2-macroglobulin (55%), as well as some cell surface proteins including talin-1 (21%), fascin (40%), and chloride intracellular channel protein 1 (51%). CONCLUSIONS. Recombinant HTRA1 cleaves RPE-secreted proteins involved in regulation of the complement pathway (clusterin, vitronectin, and fibromodulin) and of amyloid deposition (clusterin, alpha2-macroglobulin, and ADAM9). These findings suggest a link between HTRA1, complement regulation, and amyloid deposition in AMD pathogenesis.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
An E,Sen S,Park SK,Gordish-Dressman H,Hathout Ydoi
10.1167/iovs.09-4853subject
Has Abstractpub_date
2010-07-01 00:00:00pages
3379-86issue
7eissn
0146-0404issn
1552-5783pii
iovs.09-4853journal_volume
51pub_type
杂志文章abstract:PURPOSE:To test the hypothesis that longitudinal differences between retinal nerve fiber layer (RNFL) birefringence, measured by scanning laser polarimetry (SLP), and RNFL thickness, measured by optical coherence tomography (OCT), are informative about the state of axonal degeneration. METHODS:Colchicine was injected ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0872
更新日期:2008-01-01 00:00:00
abstract:PURPOSE:To visualize changes in deep optic nerve head (ONH) structures following glaucoma surgery using (3-dimensional [3D]) swept-source optical coherence tomography (SS-OCT) and to determine the clinical and structural factors associated with postoperative lamina cribrosa (LC) and prelaminar neural tissue (PLT) chang...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-11897
更新日期:2014-01-23 00:00:00
abstract:PURPOSE:Retinal injuries that affect the photoreceptors and/or the retinal pigment epithelium (RPE) may result in the leakage of retinal proteins into the systemic circulation. This study was designed to determine whether an immune response is elicited after an acute retinal injury resulting in circulating anti-retinal...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-7685
更新日期:2012-04-06 00:00:00
abstract:PURPOSE:Retinal ganglion cells die by apoptosis during development and after trauma such as axonal damage and exposure to excitotoxins. Apoptosis is associated with changes in the expression of genes that regulate this process. The genes that regulate apoptosis in retinal ganglion cells have not been characterized prim...
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 determine whether a better IOP reduction can be observed in conscious, normotensive monkeys treated with ONO-9054, a novel dual EP3 and FP receptor agonist, compared with prostaglandin F2α analogs. METHODS:The binding affinities and agonistic activities of ONO-AG-367, a carboxy...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-16181
更新日期:2015-04-01 00:00:00
abstract::The hypotensive effect of ascorbate on intraocular pressure has been reported following topical application, oral administration, or anterior chamber infusion in animals. The present report describes the correlation of aqueous humor ascorbate concentration with intraocular pressure as well as outflow facility in vivo....
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1978-08-01 00:00:00
abstract:PURPOSE:To determine the association between ocular dominance and spherical or astigmatic anisometropia, age, and sex. METHODS:Medical records of 10,264 myopic refractive surgery candidates were filtered. Ocular dominance was assessed with the hole-in-the-card test. Manifest refractive error was measured in each subje...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8131
更新日期:2011-11-25 00:00:00
abstract:PURPOSE:This study investigated a novel motion-on-color paradigm to functionally isolate the magnocellular pathway and evaluate its diagnostic value in preperimetric glaucoma patients. METHODS:Thirty patients with preperimetric primary open-angle glaucoma and 30 controls participated in this study. They were tested in...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-16394
更新日期:2015-07-01 00:00:00
abstract:PURPOSE:To determine whether dexamethasone (DEX)-induced ocular hypertension (OHT) in mice mimics the hallmarks of steroid-induced glaucoma (SIG) in humans, including reduced conventional outflow facility (C), increased extracellular matrix (ECM), and myofibroblasts within the outflow pathway. METHODS:Osmotic mini-pum...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-14429
更新日期:2014-07-15 00:00:00
abstract:PURPOSE:The phenotype of specialized cells arises, in part, from their characteristic gene expression patterns. Retinal ganglion cells (RGCs) are of wide interest in neuroscience and die in glaucoma and other optic neuropathies. In this study the genes expressed by RGCs were profiled by expressed sequence tag (EST) ana...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-1391
更新日期:2004-08-01 00:00:00
abstract:PURPOSE:To examine the relationship between circulating inflammatory markers, hemostatic factors, and age-related maculopathy (ARM). METHODS:A population-based, cross-sectional case-control study drawn from the Blue Mountains Eye Study included 159 early and 38 late ARM cases, and 433 controls matched for age, gender,...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0223
更新日期:2007-05-01 00:00:00
abstract:PURPOSE:To compare the diagnostic value of Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fiber layer thickness (RNFLT) in patients with ocular hypertension, preperimetric, and perimetric glaucoma. METHODS:One hundred eighty-one eyes consisting of 40 healthy controls, 41 ocular hypertensive sub...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,随机对照试验
doi:10.1167/iovs.15-18906
更新日期:2016-07-01 00:00:00
abstract:Purpose:Intraocular pressure (IOP), the primary risk factor for primary open-angle glaucoma, is determined by resistance to aqueous outflow through the trabecular meshwork (TM). IOP homeostasis relies on TM responses to mechanical stretch. To model the effects of elevated IOP on the TM, this study sought to identify co...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.5.2
更新日期:2020-05-11 00:00:00
abstract:PURPOSE:To identify the prognostic value of extraocular extension in enucleated uveal melanoma (UM) patients and to correlate extraocular extension to chromosomal aberrations, metastasis-free survival (MFS), and clinico-histopathological risk factors. METHODS:Retrospective study of patients with UM treated with enucle...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-13670
更新日期:2014-03-04 00:00:00
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 ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-1062
更新日期:2007-04-01 00:00:00
abstract:OBJECTIVE:To investigate the role of macrophages in the development of laser-induced choroidal neovascularization (CNV) by selective depletion with liposomal clodronate (Cl(2)MDP-LIP). METHODS:Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice. Animals were treated with intravenous (IV) and/or su...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0097
更新日期:2003-08-01 00:00:00
abstract:PURPOSE:To evaluate the importance of lens epithelial cell death in age-related cataract. To determine whether the large percentage of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)-positive lens epithelial cells previously reported in human capsulotomy specimens results from apopto...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-12-01 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::Acute laser injury to the tapetum of the feline retina produces thrombosis of the choriocapillaris. Early changes are characterized by the appearance of platelet-fibrin thrombi within capillary loops and disruption of endothelial integrity. By 4 days, thrombi have disappeared, and the endothelium shows regenerative ch...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::Long-term S-antigen (S-Ag) specific T lymphocyte lines can induce experimental autoimmune uveoretinitis (EAU) when transferred into naive rats systemically or intravitreally. The uveitogenic lymphocyte line (ThS) stains positively for the ART 18 (IL-2 receptor) and W3/25 (T helper/inducer); negatively for OX6 (RT1B) a...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract:Purpose:Diabetes causes dysfunction in the retinal mitochondria and increases base mismatches in their DNA (mtDNA). The enzyme responsible for repairing the base mismatches, MutL homolog 1 (Mlh1), is compromised. Diabetes also favors many epigenetic modifications and activates DNA methylation machinery, and Mlh1 has a ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.19-27602
更新日期:2019-09-03 00:00:00
abstract:Purpose:We compare the choroidal vascular area between Bietti crystalline dystrophy (BCD) patients with CYP4V2 mutations, retinitis pigmentosa (RP) patients with EYS mutations, and normal controls, and investigate the correlation between choroidal vascular area and associated parameters. Methods:This prospective case-...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-21515
更新日期:2017-08-01 00:00:00
abstract:PURPOSE:To test the effect of valacyclovir alone and with aspirin on the asymptomatic shedding of HSV-1 DNA in tears and saliva of healthy individuals. METHOD. The subjects (n = 45) were randomized into three groups without regard to age, sex, or race. Group 1 (n = 14) received the placebo, group 2 (n = 15) received a ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,随机对照试验
doi:10.1167/iovs.09-3729
更新日期:2009-12-01 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 determine whether gene expression changes occur in the trabecular meshwork (TM) of cow eyes with steroid-induced intraocular pressure (IOP) elevation. METHODS:Adult female Braford cows (n = 4) were subjected to uniocular prednisolone acetate treatment for 6 weeks. IOP was monitored with an applanation tonom...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-7563
更新日期:2011-11-07 00:00:00
abstract:PURPOSE:To compare the effects of early, mid, and late subconjunctival injection of bevacizumab on corneal neovascularization (NV) and conjunctivalization in a rabbit limbal insufficiency model. METHODS:Limbal insufficiency was created surgically, and subconjunctival injections of 2.5 mg bevacizumab twice weekly for 1...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4571
更新日期:2010-12-01 00:00:00
abstract:PURPOSE:To describe and interpret "choroidal caverns," an unreported optical coherence tomography (OCT) finding in the choroid of patients with geographic atrophy (GA) secondary to atrophic AMD. METHODS:Retrospective analysis of patients with GA. Main outcomes measures included estimation of the prevalence of choroida...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-19083
更新日期:2016-05-01 00:00:00
abstract:PURPOSE:To compare structural properties from spectral-domain optical coherence tomography (SDOCT) and psychophysical measures from a subset of patients enrolled in a larger multicenter natural history study of X-linked retinoschisis (XLRS). METHODS:A subset of males (n = 24) participating in a larger natural history ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:10.1167/iovs.15-18354
更新日期:2016-02-01 00:00:00
abstract::Nonenzymatic glycated lens alpha-crystallin, isolated from human diabetic cataract lenses, does not differ in subunit size and secondary structure from nonglycated alpha-crystallin. The tertiary structure, however, has undergone a significant change as reflected in the changes of near-ultraviolet (UV) circular dichroi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract:PURPOSE:To determine the involvement of rat kallikrein-binding protein (RKBP) in the development of diabetic retinopathy. METHODS:Diabetes was induced by streptozotocin (STZ) (55 mg/kg body weight in 0.05 M citrate buffer, pH 4.5) in male Sprague-Dawley rats (150 to 175 g, 6 weeks old) as confirmed by hyperglycemia an...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00