Proteomics Analysis of Molecular Risk Factors in the Ocular Hypertensive Human Retina.

Abstract:

PURPOSE:To better understand ocular hypertension-induced early molecular alterations that may determine the initiation of neurodegeneration in human glaucoma, this study analyzed retinal proteomic alterations in the ocular hypertensive human retina. METHODS:Retina samples were obtained from six human donors with ocular hypertension (without glaucomatous injury) and six age- and sex-matched normotensive controls. Retinal proteins were analyzed by two-dimensional LC-MS/MS (liquid chromatography and linear ion trap mass spectrometry) using oxygen isotope labeling for relative quantification of protein expression. Proteomics data were validated by Western blot and immunohistochemical analyses of selected proteins. RESULTS:Out of over 2000 retinal proteins quantified, hundreds exhibited over 2-fold increased or decreased expression in ocular hypertensive samples relative to normotensive controls. Bioinformatics linked the proteomics datasets to various pathways important for maintenance of cellular homeostasis in the ocular hypertensive retina. Upregulated proteins included various heat shock proteins, ubiquitin proteasome pathway components, antioxidants, and DNA repair enzymes, while many proteins involved in mitochondrial oxidative phosphorylation exhibited downregulation in the ocular hypertensive retina. Despite the altered protein expression reflecting intrinsic adaptive/protective responses against mitochondrial energy failure, oxidative stress, and unfolded proteins, no alterations suggestive of an ongoing cell death process or neuroinflammation were detectable. CONCLUSIONS:This study provides information about ocular hypertension-related molecular risk factors for glaucoma development. Molecular alterations detected in the ocular hypertensive human retina as opposed to previously detected alterations in human donor retinas with clinically manifest glaucoma suggest that proteome alterations determine the individual threshold to tolerate the ocular hypertension-induced tissue stress or convert to glaucomatous neurodegeneration when intrinsic adaptive/protective responses are overwhelmed.

authors

Yang X,Hondur G,Li M,Cai J,Klein JB,Kuehn MH,Tezel G

doi

10.1167/iovs.15-17294

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

5816-30

issue

10

eissn

0146-0404

issn

1552-5783

pii

2436720

journal_volume

56

pub_type

杂志文章
  • Surface-modified electrospun poly(epsilon-caprolactone) scaffold with improved optical transparency and bioactivity for damaged ocular surface reconstruction.

    abstract:PURPOSE:The purpose of this study was to modify and functionalize the surface of synthetic poly-ε-caprolactone (PCL) nanofibrous scaffolds to improve their biocompatibility in order to provide better "cell-substrate" interaction. METHODS:Poly-ε-caprolactone solution was electrospun and its surface functionality was mo...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.13-12727

    authors: Sharma S,Gupta D,Mohanty S,Jassal M,Agrawal AK,Tandon R

    更新日期:2014-02-12 00:00:00

  • Retinal damage by air infusion during vitrectomy in rabbit eyes.

    abstract:PURPOSE:Visual field defects after vitrectomy can be seen after any surgery involving fluid-air exchange. To elucidate the effect during surgery of the infused air on the retina, the present study investigated the changes in the morphology of the rabbit retina induced by air infusion and the changes resulting from vary...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Hasumura T,Yonemura N,Hirata A,Murata Y,Negi A

    更新日期:2000-12-01 00:00:00

  • The Effect of Light Level and Small Pupils on Presbyopic Reading Performance.

    abstract:Purpose:To examine the impact of small pupils and light levels on reading performance of distance-corrected presbyopes. To determine whether small pupils would enable presbyopes to read at near even at low light levels. Methods:To establish the lower range of text luminances, we quantified the space-averaged luminance...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.16-20008

    authors: Xu R,Gil D,Dibas M,Hare W,Bradley A

    更新日期:2016-10-01 00:00:00

  • Two types of visual dysfunction in autosomal dominant retinitis pigmentosa.

    abstract::Visual thresholds and rhodopsin levels were determined in nine subjects with autosomal dominant retinitis pigmentosa. The subjects fell into two groups, corresponding to two subtypes of the disease revealed by two-color, dark-adapted static perimetry. In the first of these subtypes, rod-mediated function was variably ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Kemp CM,Jacobson SG,Faulkner DJ

    更新日期:1988-08-01 00:00:00

  • Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjögren syndrome.

    abstract:PURPOSE:To determine whether the relative amounts of mucin mRNA in the conjunctival epithelium and mucin protein in the tears are altered in patients with Sjögren syndrome compared with healthy individuals. METHODS:Tear fluid was collected from the inferior fornix of normal subjects (n = 17) and patients with Sjögren ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Argüeso P,Balaram M,Spurr-Michaud S,Keutmann HT,Dana MR,Gipson IK

    更新日期:2002-04-01 00:00:00

  • Metipranolol blunts nitric oxide-induced lipid peroxidation and death of retinal photoreceptors: a comparison with other anti-glaucoma drugs.

    abstract:PURPOSE:To determine the effect of the nitric oxide donor sodium nitroprusside (SNP) on rat retinas and to see whether detrimental changes could be attenuated by known antiglaucoma drugs. METHODS:SNP was injected into the rat eye and retinas were analyzed by the terminal-deoxynucleotidyl transferase dUTP-linked nick e...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.04-0147

    authors: Osborne NN,Wood JP

    更新日期:2004-10-01 00:00:00

  • The reliability of a video-enhanced Hirschberg test under clinical conditions.

    abstract:PURPOSE:To examine the reliability and usefulness of a video-based Hirschberg test under clinical conditions. METHODS:The authors estimated ocular deviation in 87 patients with strabismus through automated analysis of corneal reflex displacement using a video refractor. The reproducibility of measurement, the comparis...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Hasebe S,Ohtsuki H,Tadokoro Y,Okano M,Furuse T

    更新日期:1995-12-01 00:00:00

  • Soluble forms of the high-affinity fibroblast growth factor receptor in human vitreous fluid.

    abstract:PURPOSE:Fibroblast growth factor-binding proteins (FGF-BPs) have been identified recently in blood and other biologic fluids and have been shown to be identical to a truncated form of the high-affinity cell surface FGF receptor. The authors examined the hypothesis that FGF-BPs also are present in human vitreous fluid. ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Hanneken A,Baird A

    更新日期:1995-05-01 00:00:00

  • Effects of cyclosporine and other immunosuppressive drugs on experimental autoimmune uveoretinitis in rats.

    abstract::Five immunosuppressive and anti-inflammatory agents were tested for their effects on development of experimental autoimmune uveoretinitis (EAU) and immune responses to S-antigen in rats immunized with this retinal antigen. When administered daily from day 0-14 after immunization, cyclosporine at 5-20 mg/Kg was nontoxi...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Mochizuki M,Nussenblatt RB,Kuwabara T,Gery I

    更新日期:1985-02-01 00:00:00

  • Genotype-phenotype correlation of mouse pde6b mutations.

    abstract:PURPOSE:To identify the underlying molecular defects causing retinal degeneration in seven N-ethyl-N-nitrosourea (ENU) induced mutant alleles of the Pde6b gene and to analyze the timescale of retinal degeneration in these new models of retinitis pigmentosa. METHODS:Conformation sensitive capillary electrophoresis and ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.05-0254

    authors: Hart AW,McKie L,Morgan JE,Gautier P,West K,Jackson IJ,Cross SH

    更新日期:2005-09-01 00:00:00

  • Variation of the axial location of Bruch's membrane opening with age, choroidal thickness, and race.

    abstract:PURPOSE:This study explores variation in the axial location of Bruch's membrane opening (BMO) to determine if this reference plane varies with age and race. METHODS:There were 168 spectral-domain optical coherence tomography (SDOCT) optic nerve head volumes that were obtained from healthy subjects and manually delinea...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章,多中心研究

    doi:10.1167/iovs.13-12937

    authors: Johnstone J,Fazio M,Rojananuangnit K,Smith B,Clark M,Downs C,Owsley C,Girard MJ,Mari JM,Girkin CA

    更新日期:2014-03-28 00:00:00

  • Pericyte chemomechanics and the angiogenic switch: insights into the pathogenesis of proliferative diabetic retinopathy?

    abstract:PURPOSE:To establish the regulatory roles that pericytes have in coordinating retinal endothelial cell (EC) growth and angiogenic potential. METHODS:Pericytes were derived from donor diabetic (DHuRP) or normal (NHuRP) human retinae, and characterized using vascular markers, coculture, contraction, morphogenesis, and p...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.14-13945

    authors: Durham JT,Dulmovits BM,Cronk SM,Sheets AR,Herman IM

    更新日期:2015-06-01 00:00:00

  • Dynamic patterns of histone lysine methylation in the developing retina.

    abstract:PURPOSE:Histone lysine methylation (HKM) is an important epigenetic mechanism that establishes cell-specific gene expression and functions in development. However, epigenetic control of retinal development is poorly understood. To study the roles of HKM in retinogenesis, the authors examined the dynamic changes of thre...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.09-4730

    authors: Rao RC,Tchedre KT,Malik MT,Coleman N,Fang Y,Marquez VE,Chen DF

    更新日期:2010-12-01 00:00:00

  • Measurement variability in Heidelberg Retina Tomograph imaging of neuroretinal rim area.

    abstract:PURPOSE:To investigate the optimal frequency of imaging during follow-up to detect glaucoma progression by characterizing variability (noise) in neuroretinal rim area (RA) measured by Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany). METHODS:RA noise was estimated from patient data and ch...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.06-0096

    authors: Owen VM,Strouthidis NG,Garway-Heath DF,Crabb DP

    更新日期:2006-12-01 00:00:00

  • Expression of MMPs and TIMPs in human pterygia and cultured pterygium epithelial cells.

    abstract:PURPOSE:Pterygia are a common, benign, fibrovascular, and infiltrative process of the corneal-conjunctival junction of unknown pathogenesis. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes active against all components of the extracellular matrix, whose activity is specifically neutralized by tissu...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Di Girolamo N,McCluskey P,Lloyd A,Coroneo MT,Wakefield D

    更新日期:2000-03-01 00:00:00

  • Phenotype in retinol deficiency due to a hereditary defect in retinol binding protein synthesis.

    abstract:PURPOSE:To describe the phenotype caused by a retinol deficiency in a family with compound heterozygous missense mutations (Ile41Asn and Gly75Asp) in the gene for serum retinol binding protein (RBP). METHODS:The two affected sisters, 17 (BR) and 13 (MR) years old, were examined clinically and with perimetry, color vis...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Seeliger MW,Biesalski HK,Wissinger B,Gollnick H,Gielen S,Frank J,Beck S,Zrenner E

    更新日期:1999-01-01 00:00:00

  • Association between ocular dominance and spherical/astigmatic anisometropia, age, and sex: analysis of 10,264 myopic individuals.

    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

    authors: Linke SJ,Baviera J,Munzer G,Steinberg J,Richard G,Katz T

    更新日期:2011-11-25 00:00:00

  • Transiently raised intraocular pressure reveals pattern electroretinogram losses in ocular hypertension.

    abstract:PURPOSE:It is known that the pattern electroretinogram (PERG) of normal subjects is reduced temporarily after short-term elevation of intraocular pressure (IOP). The authors evaluated PERG changes in ocular hypertension during and after transient IOP elevation. METHODS:Steady state (8 Hz) PERGs to sinusoidal gratings ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Colotto A,Falsini B,Salgarello T,Buzzonetti L,Cermola S,Porrello G

    更新日期:1996-12-01 00:00:00

  • RhoA inactivation prevents photoreceptor axon retraction in an in vitro model of acute retinal detachment.

    abstract:PURPOSE:An early injury response to retinal detachment is disruption of synaptic connectivity between photoreceptors and second-order neurons. Most dramatic is the retraction of rod cell axons and their terminals away from the outer synaptic layer and toward their cell bodies. This study tested whether axonal retractio...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.10-5744

    authors: Fontainhas AM,Townes-Anderson E

    更新日期:2011-02-01 00:00:00

  • Retinal Manifestations of Mitochondrial Oxidative Phosphorylation Disorders.

    abstract:Purpose:The purpose of this paper was to discuss manifestations of primary mitochondrial dysfunctions and whether the retinal pigment epithelium or the photoreceptors are preferentially affected. Methods:A retrospective analysis was performed of patients with clinically and laboratory confirmed diagnoses of maternally...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.61.12.12

    authors: Oh JK,Lima de Carvalho JR Jr,Nuzbrokh Y,Ryu J,Chemudupati T,Mahajan VB,Sparrow JR,Tsang SH

    更新日期:2020-10-01 00:00:00

  • Neurosteroids are endogenous neuroprotectants in an ex vivo glaucoma model.

    abstract:PURPOSE:Allopregnanolone is a neurosteroid and powerful modulator of neuronal excitability. The neuroprotective effects of allopregnanolone involve potentiation of γ-aminobutyric acid (GABA) inhibitory responses. Although glutamate excitotoxicity contributes to ganglion cell death in glaucoma, the role of GABA in glauc...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.14-15624

    authors: Ishikawa M,Yoshitomi T,Zorumski CF,Izumi Y

    更新日期:2014-11-18 00:00:00

  • Laser densitometric analysis of class I HLA antigen expression by corneal epithelium.

    abstract::Laser densitometric analysis of immunoperoxidase stained tissue was used to quantitate class I HLA (HLA-A,B,C) antigen expression by human corneal epithelium. Frozen sections of human donor corneas stored in modified McCarey-Kaufman medium for less than 24 hr were evaluated for class I HLA antigen by an indirect immun...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Dreizen NG,Whitsett CF,Austin GE,Stulting RD

    更新日期:1986-06-01 00:00:00

  • Vision- and health-related quality of life in patients with visual field loss after postchiasmatic lesions.

    abstract:PURPOSE:The purpose of the study was to assess vision-related quality of life (QoL) in patients with visual field loss (VFL) after lesions of the postchiasmatic visual pathway and to investigate the influence of VFL and reduced visual acuity (VA) on vision-related QoL. METHODS:In 312 patients with postchiasmatic damag...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-2519

    authors: Gall C,Lucklum J,Sabel BA,Franke GH

    更新日期:2009-06-01 00:00:00

  • Long-term reduction in infrared autofluorescence caused by infrared light below the maximum permissible exposure.

    abstract:PURPOSE:Many retinal imaging instruments use infrared wavelengths to reduce the risk of light damage. However, we have discovered that exposure to infrared illumination causes a long-lasting reduction in infrared autofluorescence (IRAF). We have characterized the dependence of this effect on radiant exposure and invest...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.13-12562

    authors: Masella BD,Williams DR,Fischer WS,Rossi EA,Hunter JJ

    更新日期:2014-05-20 00:00:00

  • Racial Differences in the Association of Anterior Lamina Cribrosa Surface Depth and Glaucoma Severity in the African Descent and Glaucoma Evaluation Study (ADAGES).

    abstract:Purpose:To determine if variation in anterior lamina cribrosa surface depth (ALCSD) differs between glaucoma patients of African (AD) and European descent (ED). Methods:A total of 178 eyes from 123 glaucoma patients in the African Descent and Glaucoma Evaluation Study (ADAGES) and Diagnostic Innovations in Glaucoma St...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.19-26645

    authors: Girkin CA,Fazio MA,Bowd C,Medeiros FA,Weinreb RN,Liebmann JM,Proudfoot J,Zangwill LM,Belghith A

    更新日期:2019-10-01 00:00:00

  • Internal reflectivity of filtering blebs versus intraocular pressure in patients with recent trabeculectomy.

    abstract:PURPOSE:The authors conducted a morphology analysis of filtering blebs with anterior segment optical coherence tomography (AS-OCT) in patients shortly after trabeculectomy to find further criteria for success or failure of a filtering bleb. METHODS:Thirty-seven patients (43 eyes) who had recently (<2 years) undergone ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.10-5520

    authors: Pfenninger L,Schneider F,Funk J

    更新日期:2011-04-14 00:00:00

  • Cholera toxin stimulates adenosine 3',5'-monophosphate synthesis and epithelial wound closure in the rabbit cornea.

    abstract::Rabbit corneas were treated in vitro and in vivo with cholera toxin (CTX), a specific and irreversible activator of adenylate cyclase. Tissue pieces incubated in vitro in the presence of 10 mug/ml CTX for 15 min continuously synthesized adenosine 3',5'-monophosphate (cyclic AMP) at an increased rate for 3 hr in the ab...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Jumblatt MM,Fogle JA,Neufeld AH

    更新日期:1980-11-01 00:00:00

  • Leakage of aquaporin 5 in the tear of dacryoadenitis mice.

    abstract:PURPOSE:The objective of this study was to investigate whether leakage of aquaporin 5 (AQP5) in tear is associated with damage of lacrimal glands (LGs) in dacryoadenitis models. METHODS:Female MRL/lpr (24-week-old), male NOD/Shi Jci (5-, 8-, and 10-week-old), female NFS/s-TX (10-week-old), and lipopolysaccharide (LPS)...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Hirai S,Ishida N,Watanabe K,Mita S

    更新日期:2000-08-01 00:00:00

  • Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18.

    abstract:PURPOSE:To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS:Multivariable Cox models were...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Davis MD,Fisher MR,Gangnon RE,Barton F,Aiello LM,Chew EY,Ferris FL 3rd,Knatterud GL

    更新日期:1998-02-01 00:00:00

  • Healing of retinal photocoagulation lesions.

    abstract:PURPOSE:To systematically assess the changes in retinal morphology during the healing of retinal photocoagulation lesions of various clinical grades. METHODS:Rabbits were irradiated with a 532-nm Nd:YAG laser with a beam diameter of 330 microm at the retinal surface, a power of 175 mW, and pulse durations between 5 an...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-1928

    authors: Paulus YM,Jain A,Gariano RF,Stanzel BV,Marmor M,Blumenkranz MS,Palanker D

    更新日期:2008-12-01 00:00:00