Heterozygous loss-of-function variants in CYP1B1 predispose to primary open-angle glaucoma.

Abstract:

PURPOSE:Although primary congenital glaucoma (PCG)-associated CYP1B1 mutations in the heterozygous state have been evaluated for association with primary open-angle glaucoma (POAG) in several small studies, their contribution to the occurrence of POAG is still controversial. The present study was conducted to determine whether heterozygous functionally characterized CYP1B1 mutations are associated with the disease in a large cohort of German patients with POAG. METHODS:The frequency of CYP1B1 variants on direct sequencing of the entire coding region was compared in 399 unrelated German patients with POAG (270, POAG; 47, JOAG; and 82, NTG) and 376 control subjects without any signs of glaucoma on ophthalmic examination. In vitro functional assays were performed and relative enzymatic activity of the CYP1B1 variants embedded in their respective background haplotypes and not previously unambiguously classified were determined, to assess their possible causative role. RESULTS:Apart from known polymorphic variants, 11 amino acid substitutions in CYP1B1 reported before, both in PCG and POAG cases, were identified. After in vitro functional assay, variants P52L and R368H showed marked reduction of activity, confirming their role as loss-of-function mutations similar to previously determined variants G61E, N203S, and G329V. In contrast, variants G168D, A443G, and A465V showed no relevant effects and were thus classified as polymorphisms. Overall, seven functionally impaired variants were present in 13 (3.6%) patients and in 1 (0.2%) control subject (P = 0.002, OR = 5.4). Reanalysis of previous studies reporting CYP1B1 mutations in patients with POAG based on updated functional validation showed a significant excess of carriers among patients compared to controls (OR = 3.85; P = 2.3 x 10(-7)). CONCLUSIONS:Heterozygous CYP1B1 mutations with absent or reduced relative enzymatic activity can be considered a risk factor for POAG.

authors

Pasutto F,Chavarria-Soley G,Mardin CY,Michels-Rautenstrauss K,Ingelman-Sundberg M,Fernández-Martínez L,Weber BH,Rautenstrauss B,Reis A

doi

10.1167/iovs.09-3880

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

249-54

issue

1

eissn

0146-0404

issn

1552-5783

pii

iovs.09-3880

journal_volume

51

pub_type

杂志文章
  • Displaced ganglion cells in the retina of the monkey.

    abstract::Horseradish peroxidase has been injected into the dorsal lateral geniculate nucleus of macaque monkeys to label ganglion cells of the retina by retrograde axoplasmic transport. Displaced ganglion cells, with somata in the inner nuclear layer and dendrites in the inner plexiform layer, were detected by virtue of their ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Bunt AH,Minckler DS

    更新日期:1977-01-01 00:00:00

  • Effects of stimulation of the ocular sympathetic nerves on IOP and aqueous humor flow.

    abstract::Ocular sympathetic nerves were stimulated chronically in awake rabbits using electrodes unilaterally implanted on the cervical sympathetic trunk. IOP was measured by pneumatonometry and aqueous inflow was measured by fluorophotometry. In each animal, continuous trains of 1 msec pulses were delivered by means of a port...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Belmonte C,Bartels SP,Liu JH,Neufeld AH

    更新日期:1987-10-01 00:00:00

  • Tetramethylpyrazine Attenuates Transdifferentiation of TGF-β2-Treated Human Tenon's Fibroblasts.

    abstract:PURPOSE:To investigate the pharmacologic effect of tetramethylpyrazine (TMP) on human Tenon's fibroblasts (HTFs), the cells implicated in scarring after filtration surgery. METHODS:Transforming growth factor-β2 (TGF-β2) was used to stimulate a fibrotic phenotype in primary HTFs, and the influence of TMP on the fibroti...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.16-19529

    authors: Cai X,Yang Y,Chen P,Ye Y,Liu X,Wu K,Yu M

    更新日期:2016-09-01 00:00:00

  • Molecular properties of wild-type and mutant betaIG-H3 proteins.

    abstract:PURPOSE:BetaIG-H3 is a TGF-beta-induced cell adhesion molecule, the mutations of which are responsible for a group of 5q31-linked corneal dystrophies. The characteristic findings in these diseases are accumulation of protein deposits of different ultrastructures. To understand the mechanisms of protein deposits in 5q31...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Kim JE,Park RW,Choi JY,Bae YC,Kim KS,Joo CK,Kim IS

    更新日期:2002-03-01 00:00:00

  • Iron induced oxidative damage as a potential factor in age-related macular degeneration: the Cogan Lecture.

    abstract::Iron is a potent generator of oxidative damage whose levels increase with age, potentially exacerbating age-related diseases. Several lines of evidence suggest that iron accumulation may be a factor in age-related macular degeneration (AMD). AMD retinas have more iron within the photoreceptors, RPE, and drusen than do...

    journal_title:Investigative ophthalmology & visual science

    pub_type:

    doi:10.1167/iovs.06-0568

    authors: Dunaief JL

    更新日期:2006-11-01 00:00:00

  • Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes.

    abstract:PURPOSE:To determine the cellular origin and the vascular endothelial growth factor (VEGF) immunoreactivity of the nonvascular stromal cells in surgically excised age-related macular degeneration (ARMD)-associated choroidal neovascular membranes (CNVMs). METHODS:Immunohistochemical analysis was performed on frozen sec...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Lopez PF,Sippy BD,Lambert HM,Thach AB,Hinton DR

    更新日期:1996-04-01 00:00:00

  • Restoration of foveal thickness and architecture after macula-off retinal detachment repair.

    abstract:PURPOSE:To investigate the foveal changes after repair of macula-off rhegmatogenous retinal detachment (RRD). METHODS:Prospective comparative case series. Twenty-four eyes of 24 patients with macula-off/fovea-on detachment (n = 9) and fovea-off detachment (n = 15) were studied. Serial optical coherence tomography (OCT...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.14-15633

    authors: dell'Omo R,Viggiano D,Giorgio D,Filippelli M,Di Iorio R,Calo' R,Cardone M,Rinaldi M,dell'Omo E,Costagliola C

    更新日期:2015-01-22 00:00:00

  • Photoreceptor characteristics in congenic strains of RCS rats.

    abstract::Three congenic Royal College of Surgeons (RCS) strains of rats have been developed: the RCS-p+ strain, which is a black-eyed dystrophic strain; the pink-eyed RCS-rdy+ strain, which is wild-type (+/+) at the retinal dystrophy (rdy) genetic locus and serves as the control for the inbred, pink-eyed RCS strain; and the bl...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: LaVail MM

    更新日期:1981-05-01 00:00:00

  • Local Modulation of Retinal Vein Tone.

    abstract:PURPOSE:To determine whether vascular tone of isolated porcine retinal veins can be modulated by tissue-generated vasoactive factors such as endothelin-1 and adenosine. Such information may be useful in understanding the role of the retinal veins in regulating blood flow, and also provide a model for investigating new ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.15-18358

    authors: Yu DY,Su EN,Cringle SJ,Morgan WH,McAllister IL,Yu PK

    更新日期:2016-02-01 00:00:00

  • Influence of the disc-fovea angle on limits of RNFL variability and glaucoma discrimination.

    abstract:PURPOSE:To determine factors affecting the disc-fovea angle (DFA), and to test the hypotheses that adjusting for DFA improves limits of retinal nerve fiber layer (RNFL) variability in normal subjects or enhances performance of RNFL measures for glaucoma detection. METHODS:Disc-fovea angle was measured on scanning lase...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.14-14962

    authors: Amini N,Nowroozizadeh S,Cirineo N,Henry S,Chang T,Chou T,Coleman AL,Caprioli J,Nouri-Mahdavi K

    更新日期:2014-10-09 00:00:00

  • Comparative analysis of repeatability of manual and automated choroidal thickness measurements in nonneovascular age-related macular degeneration.

    abstract:PURPOSE:We compared the reproducibility and mutual agreement of the subfoveal choroidal thickness measurements by expert raters and an automated algorithm in enhanced depth imaging optical coherence tomography (EDI-OCT) images of eyes with nonneovascular age-related macular degeneration (AMD). METHODS:We recruited 44 ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 临床试验,杂志文章

    doi:10.1167/iovs.12-11521

    authors: Lee S,Fallah N,Forooghian F,Ko A,Pakzad-Vaezi K,Merkur AB,Kirker AW,Albiani DA,Young M,Sarunic MV,Beg MF

    更新日期:2013-04-23 00:00:00

  • DNA repair synthesis in the rat retina following in vivo exposure to 300-nm radiation.

    abstract::Quantitative autoradiography was used to study the incorporation of 3H-thymidine into the retina of albino rats following in vivo exposure to 300-nm radiation. Relative to background labeling in unexposed eyes, there was 8-20 times as much label per unit area in the outer nuclear layer, inner nuclear layer, and gangli...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Rapp LM,Jose JG,Pitts DG

    更新日期:1985-03-01 00:00:00

  • Cytokines in autoimmune lacrimal gland disease in MRL/MpJ mice.

    abstract:PURPOSE:MRL/MpJ-+/+ (MRL/+) and MRL/MpJ-lpr/lpr (MRL/lpr) mice show spontaneous development of a T-cell-driven lacrimal gland inflammation that is a model for Sjögren syndrome. The lacrimal gland lesions in these mice were evaluated by quantitative RT-PCR for selected cytokine mRNA for the relative contributions of T-h...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Jabs DA,Prendergast RA,Rorer EM,Hudson AP,Whittum-Hudson JA

    更新日期:2001-10-01 00:00:00

  • Sister chromatid exchange induced by X-irradiation of retinoblastoma lymphocytes.

    abstract::Lymphocyte cultures were employed to assess the degree of spontaneous and induced chromosomal fragility in retinoblastoma. Sister chromatid exchange (SCEs) were scored in metaphases. Three unilateral, three bilateral, eleven family members and controls were studied. Retinoblastoma (RB) lymphocytes did not exhibit incr...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Abramovsky-Kaplan I,Jones IS

    更新日期:1984-06-01 00:00:00

  • Simultaneous analysis of multiple cytokines in the vitreous of patients with sarcoid uveitis.

    abstract:PURPOSE:Levels of some cytokines are significantly higher in the vitreous fluid of patients with acute uveitis than in normal vitreous fluid. The authors sought to determine which proinflammatory cytokines were upregulated in the vitreous fluid of patients with ocular sarcoidosis. METHODS:Samples of vitreous fluid wer...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.11-9244

    authors: Nagata K,Maruyama K,Uno K,Shinomiya K,Yoneda K,Hamuro J,Sugita S,Yoshimura T,Sonoda KH,Mochizuki M,Kinoshita S

    更新日期:2012-06-20 00:00:00

  • Polyphosphate kinase 1 and the ocular virulence of Pseudomonas aeruginosa.

    abstract:PURPOSE:To determine the role of polyphosphate kinase 1 (PPK1) in the ocular virulence of Pseudomonas aeruginosa. METHODS:Using a mouse model of infection, P. aeruginosa strains PAO1, PAOM5 (an isogenic mutant of PAO1 deficient in PPK1), and PAOM5+PPK1 (the mutant complemented with PPK1 on plasmid pHEPAK11) were compa...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.04-0340

    authors: Parks QM,Hobden JA

    更新日期:2005-01-01 00:00:00

  • Epiretinal membrane inflammatory cell density might reflect the activity of proliferative diabetic retinopathy.

    abstract:PURPOSE:Diabetic retinopathy (DR) has features of chronic low-grade inflammation. The purpose of our study was to investigate whether the presence of inflammatory cells in fibrovascular membranes (FVMs) from patients with proliferative diabetic retinopathy (PDR) is associated with the activity of PDR and visual acuity ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.13-13634

    authors: Urbančič M,Štunf Š,Milutinović Živin A,Petrovič D,GlobočnikPetrovič M

    更新日期:2014-11-25 00:00:00

  • Tonometric changes of latanoprost-induced intraocular pressure reduction after photorefractive keratectomy.

    abstract:PURPOSE:To assess whether tonometric measurements of the drop in intraocular pressure (IOP) induced by 0.005% latanoprost are modified after photorefractive keratectomy (PRK). METHODS:Data from 24 randomly selected eyes of 24 patients (12 men and 12 women, mean age +/- SD: 31.7 +/- 6.2 years) who were undergoing bilat...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.03-0625

    authors: Tamburrelli C,Vaiano AS,Salgarello T,Caputo CG,Scullica L

    更新日期:2004-03-01 00:00:00

  • Neuropeptide Y and the retinal pigment epithelium: receptor subtypes, signaling, and bioelectrical responses.

    abstract:PURPOSE:To characterize the potential for neuropeptide Y (NPY) signaling in the retinal pigment epithelium (RPE) by identifying the NPY receptor subtypes present, determining the effect of NPY on second-messenger production and membrane conductance, and establishing the neural retina as a site of NPY gene expression. ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Ammar DA,Hughes BA,Thompson DA

    更新日期:1998-09-01 00:00:00

  • Deficient Binocular Combination of Second-Order Stimuli in Amblyopia.

    abstract:PURPOSE:Sensory imbalances in humans with amblyopia have been well documented using luminance-modulated (first-order) stimuli. However, little is known regarding whether there is a deficient binocular combination in amblyopes for stimuli defined by modulations in contrast (second-order stimuli). To address this, we ask...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.15-18253

    authors: Zhou J,Liu R,Feng L,Zhou Y,Hess RF

    更新日期:2016-04-01 00:00:00

  • Differential distribution of CaM kinases and induction of c-fos expression by flashing and sustained light in rat retinal cells.

    abstract:PURPOSE:To examine the expression of c-fos proto-oncogene and phosphorylation of cAMP responsive element binding (CREB) protein in the rat retina after changes in the light-dark condition. METHODS:Rats were exposed to both steady light and flashing light and were killed at the end of light exposure. The retinas were a...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Yoshida K,Imaki J,Fujisawa H,Harada T,Ohki K,Matsuda H,Hagiwara M

    更新日期:1996-01-01 00:00:00

  • Elastin content of the scleral spur, trabecular mesh, and sclera.

    abstract::The scleral spur and trabecular mesh of the human eye contain approximately 5% elastic tissue. Elastic tissue forms less than 2% of the sclera. ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Moses RA,Grodzki WJ Jr,Starcher BC,Galione MJ

    更新日期:1978-08-01 00:00:00

  • Dissociation between prostaglandin levels and blood flow to the retina and choroid in the newborn pig after nonsteroidal antiinflammatory drugs.

    abstract::To assess whether prostaglandins contribute to the control of basal retinal and choroidal hemodynamics, retinal (RBF) and choroidal blood flow (ChBF) were measured by a microsphere technique in 1- to 4-day-old pigs before and after (at 20 and 60 min) administration of indomethacin (0.3 mg/kg, n = 6 or 10 mg/kg, n = 5)...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Parys-Van Ginderdeuren R,Malcolm D,Varma DR,Aranda JV,Chemtob S

    更新日期:1992-11-01 00:00:00

  • Effects of ischemic preconditioning and bevacizumab on apoptosis and vascular permeability following retinal ischemia-reperfusion injury.

    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

    authors: Abcouwer SF,Lin CM,Wolpert EB,Shanmugam S,Schaefer EW,Freeman WM,Barber AJ,Antonetti DA

    更新日期:2010-11-01 00:00:00

  • The effects of 5-fluorouracil on ocular tissues in vitro and in vivo after controlled release from a multifunctional implant.

    abstract:PURPOSE:To evaluate the effects of 5-fluorouracil (5-FU) on ocular cells in vitro and the effects of degradable 5-FU-loaded poly(DL-lactide-co-glycolide; PDLGA) 50:50 implant in the rabbit eye in vivo. METHODS:Cytotoxicity was assessed with a tetrazolium salt WST-1 cell proliferation/viability test and a lactate dehyd...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-3016

    authors: Huhtala A,Rönkkö S,Teräsvirta M,Puustjärvi T,Sihvola R,Vehanen K,Laukkanen A,Anttila J,Urtti A,Pohjonen T,Uusitalo H

    更新日期:2009-05-01 00:00:00

  • Reduced photoreceptor damage after photodynamic therapy through blockade of nitric oxide synthase in a model of choroidal neovascularization.

    abstract:PURPOSE:To investigate the role of nitric oxide synthase (NOS) in photoreceptor degeneration associated with photodynamic therapy (PDT) in a laser-induced model of choroidal neovascularization (CNV). METHODS:PDT was performed in monkey and Brown Norway rats with laser-induced CNV. L-NAME, a NOS inhibitor, or saline wa...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.06-0979

    authors: She H,Nakazawa T,Matsubara A,Hisatomi T,Young TA,Michaud N,Connolly E,Hafezi-Moghadam A,Gragoudas ES,Miller JW

    更新日期:2007-05-01 00:00:00

  • Clearance and localization of intravitreal liposomes in the aphakic vitrectomized eye.

    abstract::The authors have examined the fate of intravitreally injected liposomes in the aphakic, vitrectomized eye of the rabbit. Liposomes labelled with 125[I]-p-hydroxybenzimidylphosphatidylethanolamine were eliminated rapidly from the intraocular fluid. Nonetheless, a significant fraction of these liposomes were found to bi...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Stern WH,Heath TD,Lewis GP,Guerin CJ,Erickson PA,Lopez NG,Hong KL

    更新日期:1987-05-01 00:00:00

  • Staining characteristics and antiviral activity of sulforhodamine B and lissamine green B.

    abstract:PURPOSE:Fluorescein and rose bengal are dyes used routinely in the examination of the ocular surface. As part of an ongoing search for a superior ophthalmic dye with optimal specificity and sensitivity and a lack of interference with subsequent viral cultures, and as part of studies that use chemical dyes to understand...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Chodosh J,Dix RD,Howell RC,Stroop WG,Tseng SC

    更新日期:1994-03-01 00:00:00

  • Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa.

    abstract:PURPOSE:To map the spatiotemporal decline in retinally driven activity in the superior colliculus (SC) of transgenic S334ter-line-3 rats that express a mutated rhodopsin, which causes photoreceptor degeneration. To determine whether transplantation of fetal retinal sheets into the subretinal space of these rats can rec...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.02-0615

    authors: Sagdullaev BT,Aramant RB,Seiler MJ,Woch G,McCall MA

    更新日期:2003-04-01 00:00:00

  • Proteoglycan composition in the human sclera during growth and aging.

    abstract:PURPOSE:Scleral proteoglycans were characterized from human donor eyes aged 2 months to 94 years to identify age-related changes in the synthesis and/or accumulation of these extracellular matrix components. METHODS:Newly synthesized proteoglycans (previously radiolabeled with 35SO4) and total accumulated scleral prot...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Rada JA,Achen VR,Penugonda S,Schmidt RW,Mount BA

    更新日期:2000-06-01 00:00:00