Abstract:
PURPOSE:Keratoconus is a progressive disorder of the cornea that can lead to severe visual impairment or blindness. Although several genomic regions have been linked to rare familial forms of keratoconus, no genes have yet been definitively identified for common forms of the disease. METHODS:Two genome-wide association scans were undertaken in parallel. The first used pooled DNA from an Australian cohort, followed by typing of top-ranked single-nucleotide polymorphisms (SNPs) in individual DNA samples. The second was conducted in individually genotyped patients, and controls from the USA. Tag SNPs around the hepatocyte growth factor (HGF) gene were typed in three additional replication cohorts. Serum levels of HGF protein in normal individuals were assessed with ELISA and correlated with genotype. RESULTS:The only SNP observed to be associated in both the pooled discovery and primary replication cohort was rs1014091, located upstream of the HGF gene. The nearby SNP rs3735520 was found to be associated in the individually typed discovery cohort (P = 6.1 × 10(-7)). Genotyping of tag SNPs around HGF revealed association at rs3735520 and rs17501108/rs1014091 in four of the five cohorts. Meta-analysis of all five datasets together yielded suggestive P values for rs3735520 (P = 9.9 × 10(-7)) and rs17501108 (P = 9.9 × 10(-5)). In addition, SNP rs3735520 was found to be associated with serum HGF level in normal individuals (P = 0.036). CONCLUSIONS:Taken together, these results implicate genetic variation at the HGF locus with keratoconus susceptibility.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Burdon KP,Macgregor S,Bykhovskaya Y,Javadiyan S,Li X,Laurie KJ,Muszynska D,Lindsay R,Lechner J,Haritunians T,Henders AK,Dash D,Siscovick D,Anand S,Aldave A,Coster DJ,Szczotka-Flynn L,Mills RA,Iyengar SK,Taylor KD,doi
10.1167/iovs.11-8261subject
Has Abstractpub_date
2011-10-31 00:00:00pages
8514-9issue
11eissn
0146-0404issn
1552-5783pii
iovs.11-8261journal_volume
52pub_type
杂志文章abstract:Purpose:This study addresses the hypothesis that age-related stresses upregulate Thy-1 in choroidal endothelial cells (CECs) and contribute to CEC activation and migration, processes important in choroidal neovascularization (CNV). Methods:Measurements were made of Thy-1 protein (Western blot) in CECs and Thy-1 mRNA (...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-19691
更新日期:2016-10-01 00:00:00
abstract:PURPOSE:We previously showed that pre-exposure of the cornea to Toll-like receptor (TLR)5 ligand flagellin induces strong protective innate defense against microbial pathogens and hypothesized that flagellin modulates gene expression at the transcriptional levels. Thus, we sought to determine the role of one transcript...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12453
更新日期:2013-11-15 00:00:00
abstract:PURPOSE:To investigate the application of anterior corneal and ocular aberrations in detecting mildly ectatic corneas. METHODS:This study retrospectively reviewed the data of 220 eyes separated into three groups by the NIDEK Corneal Navigator System automated corneal classification software: normal (N) (n = 123); form...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8803
更新日期:2012-05-17 00:00:00
abstract:PURPOSE:The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis. METHODS:Vitreous samples were collected from office-based needle aspiration and the rate of adverse events during follow-up was reviewed. The vitre...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-18721
更新日期:2016-06-01 00:00:00
abstract:PURPOSE:To develop structural markers of early glaucomatous optic nerve damage with confocal scanning laser ophthalmoscopy. METHODS:Custom software was developed to analyze the images of 53 patients with open-angle glaucoma and 43 healthy subjects (matched for age, race, and refractive error), with images acquired wit...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract:PURPOSE:The structure of collagen lamellae in the anterior stroma of the human cornea is thought to be an important determinant of corneal rigidity. The three-dimensional structure of such collagen lamellae in normal human corneas was examined. METHODS:The anterior portion of 27 normal human corneas was obtained from ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5657
更新日期:2011-02-16 00:00:00
abstract:PURPOSE:The aim of the present study was to use an in vivo model of retinal excitotoxicity to investigate the neuroprotective effect of somatostatin (SRIF)-ergic agents. METHODS:Adult Sprague-Dawley rats (weight range, 250-300 g) intravitreally received (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hyd...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-1644
更新日期:2008-07-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate a DNA dot hybridization assay (DHA) for assessing bacterial bioburden in orthokeratology lens (OK) storage cases. METHODS:Forty-one OK wearers participated in this study. The dot hybridization assay was used to assess the bacterial bioburden of OK after removal and 6-hour ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-15920
更新日期:2014-12-23 00:00:00
abstract:PURPOSE:Cigarette smoking is the most consistent risk factor for age-related macular degeneration (AMD), especially the choroidal neovascularization (CNV)-mediated exudative type. Dioxins and dioxin-like compounds have various effects on living organisms and are also contained in cigarette smoke. However, the effects o...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-2299
更新日期:2009-07-01 00:00:00
abstract::Previous studies have used Badal laser optometry to demonstrate significant variance in the distribution of tonic (or "dark-focus") resting positions of accommodation (TA) for groups of observers. This study investigates whether individual differences in TA are due to individual differences in autonomic tone of the ci...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00
abstract:PURPOSE:To determine protective properties of recombinant TCR ligands (RTLs) as a new treatment for experimental autoimmune anterior uveitis (AU). RTLs comprise the rat RT1.B beta1alpha1 domains, linked either to the guinea pig MBP69-89 peptide (RTL201), to the corresponding rat MBP69-89 peptide (RTL200), or to the car...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1242
更新日期:2006-06-01 00:00:00
abstract::An ultrasonic pachometer was used to measure the central, mid-peripheral, and peripheral thickness in 17 locations across the corneas of 12 adult New Zealand Albino rabbit eyes. The mean thickness at each location was entered into a microcomputer to generate a three-dimensional plot of corneal thickness. The rabbit co...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-10-01 00:00:00
abstract:Purpose:To assess the presence of binocular gain in macular telangiectasia type 2 (MacTel) and its correlation to paracentral scotomas. Methods:Sixty-eight patients with MacTel were consecutively recruited for a cross-sectional analysis. Best-corrected visual acuity (BCVA), reading acuity, and reading speed were teste...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.18-26414
更新日期:2019-09-03 00:00:00
abstract::Cataracts removed intracapsularly by cryoprobe technique from human diabetics were analyzed for sugars and polyols by gas liquid chromatography. The contents of sorbitol and fructose of lenses followed blood glucose levels at least up to 250 mg/dl. Studies indicate that human lens is capable of synthesizing substantia...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract:PURPOSE:To investigate the alterations in gene expression when human retinal pigment epithelial (RPE) cells in culture are treated with vitreous as a model for the changes that occur in proliferative vitreoretinopathy. METHODS:Human RPE cells were cultured with or without human vitreous or collagen. RNA was extracted ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-0528
更新日期:2003-04-01 00:00:00
abstract:Purpose:The purpose of this study was to establish and analyze a cell model of Leber congenital amaurosis type 16 (LCA16), which is caused by mutations in the KCNJ13 gene encoding Kir7.1, an inward-rectifying potassium ion channel. Methods:The two guide RNAs specific to the target sites in the KCNJ13 gene were designe...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.5.38
更新日期:2020-05-11 00:00:00
abstract:PURPOSE:Adeno-associated viral (AAV) vectors have been used to express several different proteins in the eye. The purpose of this study was to determine whether AAV-mediated intraocular gene transfer of pigment epithelium-derived factor (PEDF) inhibits the development of choroidal neovascularization (CNV) in a murine m...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract:PURPOSE:To investigate the molecular mechanism of Rho-associated kinase (ROCK) inhibitors Y-27632 and Y-39983 on corneal endothelial cell (CEC) proliferation and their wound-healing effect. METHODS:The expression of G1 proteins of the cell cycle and expression of phosphorylated Akt in monkey CECs (MCECs) treated with ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12225
更新日期:2014-01-15 00:00:00
abstract:PURPOSE:Videokeratography of early keratoconus may be difficult to distinguish from contact lens-induced corneal warpage, even by experienced examiners. Furthermore, topographic irregularity may be judged inconsistently if quantitative standards are not applied. Quantitative measures based on videokeratographic data we...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract:PURPOSE:Liquid perfluorocarbons are used as temporary vitreous substitutes in the surgical management of complicated retinal detachment. The purpose of this study was to determine if physiologic benefits could also be derived from the high oxygen solubility of perfluorochemicals relative to vitreous, especially during ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To explore differences in optic disc tilt and torsion between normal control and glaucoma subjects, and to determine whether the direction of optic disc tilt is consistent with the initial location of glaucomatous visual field (VF) defect. METHODS:Glaucoma patients with isolated superior or inferior hemifield ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-14663
更新日期:2014-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-17604
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:The authors' previous models predicted local formation of diabetic retinopathy (DR) in adults with diabetes and existing retinopathy. Here they derived a multivariate model for local prediction of DR onset in patients with no previous retinopathy. METHODS:Seventy-eight eyes from 41 diabetes patients were teste...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5931
更新日期:2011-02-09 00:00:00
abstract::The microvascular permeability response of the guinea pig conjunctiva to sulfidopeptide leukotrienes (LTs) was quantified as extravasation of radiolabeled bovine serum albumin. The LTs were potent inducers of increased microvascular permeability, with relative potencies LTE4 greater than or equal to LTD4 greater than ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-01-01 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:This study describes the expression and distribution of arrestin, phosducin, and recoverin in the cone-dominant retina of the ground squirrel Spermophilus tridecemlineatus. METHODS:mRNA expression was studied by blot hybridization of ground squirrel retinal RNA, with human and murine RNA as controls. The distr...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract:PURPOSE:To evaluate age-related Meibomian gland (MG) changes by in vivo laser scanning confocal microscopy (LSCM). METHODS:Asymptomatic healthy subjects (n=100, age range 20-83 years) with an Ocular Surface Disease Index score of less than 13 were consecutively enrolled. Two additional groups, one composed of subjects...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-11914
更新日期:2013-07-16 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.18-23954
更新日期:2018-11-01 00:00:00
abstract:PURPOSE:Best disease is a monogenic macular degeneration caused mainly by heterozygous mutations in the BEST1 gene. The objective was to characterize the molecular and clinical features of patients with the classical form of Best disease that is inherited in an autosomal recessive mode. METHODS:Clinical evaluation inc...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-7174
更新日期:2011-07-18 00:00:00
abstract::Monoclonal antibody to HSV glycoprotein D was derivatized with palmitic acid and incorporated into liposomes. These immunoliposomes bound specifically to intact mouse corneas infected with HSV-1 in vitro. Furthermore, in yield reduction assays, anti-gD immunoliposomes loaded with acyclovir proved far more effective at...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00