Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea.

Abstract:

PURPOSE:The secreted Ly6/uPAR-related protein-1 (Slurp1), associated with the hyperkeratotic disorder mal de Meleda, is abundantly expressed in corneas. Here, we examine its corneal expression and functions. METHODS:Gene expression was quantified by quantitative PCR (qPCR), immunoblots, and immunofluorescent staining. Effect of Kruppel-like factor 4 (Klf4) on Slurp1 promoter was evaluated by chromatin immunoprecipitation (ChIP) and transient transfections. Adenoviral vectors were used to express Slurp1 in corneas. Leukocytic infiltration in bacterial lipopolysaccharide (LPS)-, herpes simplex virus type 1 (HSV-1)-, or adenovirus (serotype 5)-treated mouse corneas was characterized by flow cytometry. RESULTS:Corneal expression of Slurp1 increased sharply upon mouse eyelid opening, concurrent with the elevated expression of Klf4. Slurp1 was significantly decreased in Klf4 conditional null (Klf4CN) corneas that displayed elevated expression of cytokines and cytokine receptors, as well as neutrophil influx consistent with a proinflammatory environment. In additional models of corneal inflammation, Slurp1 expression was abrogated within 24 hours of LPS injection or HSV-1 or adenoviral infection, accompanied by a predominantly neutrophilic infiltrate. Neutrophilic infiltration was enhanced in HSV-1-infected Klf4CN corneas lacking Slurp1. SLURP1 promoter activity was stimulated by KLF4, suppressed by IL-4, IL-13, and TNFα, and unperturbed by IFN-γ. Slurp1 downregulation and neutrophil influx were comparable in HSV-1-infected wild-type (WT) and Ifng-/- mouse corneas. Mouse corneas infected with Slurp1-expressing adenoviral vectors displayed reduced signs of inflammation and restricted neutrophilic infiltration compared with those infected with control vectors. CONCLUSIONS:Klf4 regulates the expression of Slurp1, a key immunomodulatory peptide that is abundantly expressed in healthy corneas and is downregulated in proinflammatory conditions.

authors

Swamynathan S,Buela KA,Kinchington P,Lathrop KL,Misawa H,Hendricks RL,Swamynathan SK

doi

10.1167/iovs.12-10759

subject

Has Abstract

pub_date

2012-12-19 00:00:00

pages

8433-46

issue

13

eissn

0146-0404

issn

1552-5783

pii

iovs.12-10759

journal_volume

53

pub_type

杂志文章
  • Retinal nerve fiber layer assessment using optical coherence tomography with active optic nerve head tracking.

    abstract:PURPOSE:To develop an eye-motion-tracking optical coherence tomographic (OCT) method and assess its effect on image registration and nerve fiber layer (NFL) thickness measurement reproducibility. METHODS:A system capable of tracking common fundus features based on reflectance changes was integrated into a commercial O...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.05-0748

    authors: Ishikawa H,Gabriele ML,Wollstein G,Ferguson RD,Hammer DX,Paunescu LA,Beaton SA,Schuman JS

    更新日期:2006-03-01 00:00:00

  • Detection efficiency of circular gratings and bandpass filtered points with randomized phase spectra.

    abstract:PURPOSE:In the studies of spatial integration an increase in the spatial extent of the stimulus usually results in a decrease in the spatial frequency bandwidth of the stimulus. The authors investigated separately the effects of these two factors on contrast detectability. METHODS:Efficiencies were measured for a circ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Kukkonen H,Näsänen R,Rovamo J

    更新日期:1994-06-01 00:00:00

  • Increase of manganese superoxide dismutase, but not of Cu/Zn-SOD, in experimental optic neuritis.

    abstract:PURPOSE:To evaluate the role of manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu/Zn-SOD) in cellular protection of the optic nerve against the oxidative injury that contributes to demyelination in experimental allergic encephalomyelitis (EAE). METHODS:Immunocytochemistry for Mn-SOD and ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Qi X,Guy J,Nick H,Valentine J,Rao N

    更新日期:1997-05-01 00:00:00

  • Corneal endothelial cell survival in organ cultures under acute oxidative stress: effect of VIP.

    abstract:PURPOSE:Human corneal endothelium, a neural crest-derived tissue, has a very limited regenerative capacity and may depend on trophic factors for its survival throughout life, as well as after injury and during storage before transplantation. The purpose of this study was to determine whether vasoactive intestinal pepti...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Koh SW,Waschek JA

    更新日期:2000-12-01 00:00:00

  • Connexin43 knockdown accelerates wound healing but inhibits mesenchymal transition after corneal endothelial injury in vivo.

    abstract:PURPOSE:To explore connexin43 (Cx43) knockdown as an efficient treatment for corneal endothelial injury in an in vivo rat corneal scrape injury model. METHODS:Scrape injury was induced in the corneal endothelium, and immunolabeling (ZO-1, alpha-SMA, Cx43) was performed to analyze changes in Cx43 expression during woun...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.07-0255

    authors: Nakano Y,Oyamada M,Dai P,Nakagami T,Kinoshita S,Takamatsu T

    更新日期:2008-01-01 00:00:00

  • The intravitreal penetration of orally administered ciprofloxacin in humans.

    abstract::To evaluate the penetration of ciprofloxacin, a new wide-spectrum oral antibiotic, into the vitreous, ciprofloxacin was administered orally to 21 patients who were scheduled to undergo vitreal surgery. Seven patients received 750 mg ciprofloxacin 4 hr before surgery (group I), seven patients received this dose 8 hr be...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Keren G,Alhalel A,Bartov E,Kitzes-Cohen R,Rubinstein E,Segev S,Treister G

    更新日期:1991-07-01 00:00:00

  • Cone versus rod disease in a mutant Rpgr mouse caused by different genetic backgrounds.

    abstract:PURPOSE:To establish mouse models for RPGR-associated diseases by generating and characterizing an Rpgr mutation (in-frame deletion of exon 4) in two different genetic backgrounds (BL/6 and BALB/c). METHODS:Gene targeting in embryonic stem (ES) cells was performed to introduce a in-frame deletion of exon 4 in the Rpgr...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-2742

    authors: Brunner S,Skosyrski S,Kirschner-Schwabe R,Knobeloch KP,Neidhardt J,Feil S,Glaus E,Luhmann UF,Rüther K,Berger W

    更新日期:2010-02-01 00:00:00

  • Biochemical activity of reactive oxygen species scavengers do not predict retinal ganglion cell survival.

    abstract:PURPOSE:Retinal ganglion cells (RGCs) die as a result of axonal injury in a variety of optic neuropathies, including glaucoma. Reactive oxygen species (ROS) act as intracellular signaling molecules and initiate apoptosis in nerve growth factor-deprived sympathetic neurons and axotomized RGCs. Determination of the role ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.05-1010

    authors: Schlieve CR,Lieven CJ,Levin LA

    更新日期:2006-09-01 00:00:00

  • Photosensitization of the lens by 8-methoxypsoralen.

    abstract::During the past decade, ambient ultraviolet radiation has been implicated in the age-related increase in fluorescence and pigmentation of the human lens nucleus. 8-Methoxypsoralen (8-MOP) (currently in vogue for the treatment of psoriasis) is a well-known photosensitizing agent. This drug lar fluorescence (360/440 nm....

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Lerman S,Jocoy M,Borkman RF

    更新日期:1977-11-01 00:00:00

  • Dark-adapted sensitivity, rhodopsin content, and background adaptation in pcd/pcd mice.

    abstract::Adaptation to steady background lights has been investigated in pcd/pcd mice, a mutant strain with retinal degeneration. The hyperbolic stimulus/response functions of the scotopic b-wave of the electroretinogram show progressive changes. For the dark-adapted eyes the decrease in log sensitivity between ages 1 and 12 m...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Fulton AB,Manning KA,Baker BN,Schukar SE,Bailey CJ

    更新日期:1982-03-01 00:00:00

  • Effect of aniseikonia on binocular function.

    abstract::The pattern reversal visual evoked response (VER) was recorded under conditions of artificially unbalanced visual input between two eyes, an aniseikonia induced by size lenses that alter the perceived retinal image size without changing refraction. At 3.0% aniseikonia binocular summation started to decrease, and at 5....

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Katsumi O,Tanino T,Hirose T

    更新日期:1986-04-01 00:00:00

  • Benefits and side effects of different vegetable oil vectors on apoptosis, oxidative stress, and P2X7 cell death receptor activation.

    abstract:PURPOSE:Ocular side effects in patients using eye drops may be due to intolerance to the vector used in eye drops. Castor oil is the commonly used lipophilic vector but has been shown to be cytotoxic. Effects on cells of four oils (olive, camelina, Aleurites moluccana, maize) were compared with those of castor oil in h...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.07-0229

    authors: Said T,Dutot M,Christon R,Beaudeux JL,Martin C,Warnet JM,Rat P

    更新日期:2007-11-01 00:00:00

  • Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations.

    abstract:PURPOSE:To study the topography of photoreceptor loss early in the course of Leber congenital amaurosis (LCA) caused by RPE65 mutations. METHODS:Young patients with RPE65-LCA (n = 9; ages, 6-17 years) were studied with optical coherence tomography (OCT) in a wide region of central retina. Outer nuclear layer (ONL) thi...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-2121

    authors: Jacobson SG,Cideciyan AV,Aleman TS,Sumaroka A,Windsor EA,Schwartz SB,Heon E,Stone EM

    更新日期:2008-10-01 00:00:00

  • Activation of Cytosolic Calpain, Not Caspase, Is Underlying Mechanism for Hypoxic RGC Damage in Human Retinal Explants.

    abstract:Purpose:Activation of proteolytic enzymes, calpains and caspases, have been observed in many models of retinal disease. We previously demonstrated calpain activation in monkey retinal explants cultured under hypoxia. However, cellular responses are often species-specific. The purpose of the present study was to determi...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.61.13.13

    authors: Kobayashi-Otsugu M,Orihara K,Nakajima E,Shearer TR,Azuma M

    更新日期:2020-11-02 00:00:00

  • Velocities of vertical saccades with different eye movement recording methods.

    abstract::Voluntary vertical saccades were recorded in five normal human subjects with electro-oculography (EOG), an infrared, limbus tracking system (IR), and a magnetic scleral search coil method. The peak velocity-amplitude relationships of up and down saccades were measured during refixations across the center of the orbit ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Yee RD,Schiller VL,Lim V,Baloh FG,Baloh RW,Honrubia V

    更新日期:1985-07-01 00:00:00

  • Corneal thickness profiles in rabbits using an ultrasonic pachometer.

    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:

    authors: Chan T,Payor S,Holden BA

    更新日期:1983-10-01 00:00:00

  • Regional differences in functional receptor distribution and calcium mobilization in the intact human lens.

    abstract:PURPOSE:To investigate regional differences in Ca(2+) mobilization kinetics in the intact human lens produced by exposure to agonists of tyrosine-kinase and G-protein-coupled receptors and to characterize the major receptor subtypes involved in Ca(2+) signaling in the different regions. METHODS:Whole human lenses were...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Collison DJ,Duncan G

    更新日期:2001-09-01 00:00:00

  • Heritability of macular pigment: a twin study.

    abstract:PURPOSE:Several studies have reported higher levels of macular pigment (MP) in association with reduced risk for age-related macular degeneration (ARMD), a disease to which there is a genetic predisposition. A classic twin study was performed to determine the heritability of MP in the healthy eye. METHODS:One hundred ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.05-0519

    authors: Liew SH,Gilbert CE,Spector TD,Mellerio J,Marshall J,van Kuijk FJ,Beatty S,Fitzke F,Hammond CJ

    更新日期:2005-12-01 00:00:00

  • Retinal colocalization and in vitro interaction of the glutamate transporter EAAT3 and the serum- and glucocorticoid-inducible kinase SGK1 [correction].

    abstract:PURPOSE:The serum- and glucocorticoid-inducible kinase SGK1 regulates several epithelial channels and transporters, the related protein kinase B (PKB) regulates glucose transport. SGK1 is expressed in the brain and could thus regulate glial and/or neuronal transport processes. The present study explores whether SGK1 is...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.03-0062

    authors: Schniepp R,Kohler K,Ladewig T,Guenther E,Henke G,Palmada M,Boehmer C,Rothstein JD,Bröer S,Lang F

    更新日期:2004-05-01 00:00:00

  • Aggregation in aqueous solutions of bovine lens gamma-crystallins: special role of gamma(s).

    abstract:PURPOSE:To study the aggregation of bovine gamma-crystallins in aqueous solutions and the effect of gamma(s)-crystallin on the aggregation of other gamma-crystallins. METHODS:Aggregation in aqueous solutions of gamma(s)-, gammaII-, and gammaIVa-crystallin was monitored by quasielastic light scattering. Aggregation in ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Liu C,Pande J,Lomakin A,Ogun O,Benedek GB

    更新日期:1998-08-01 00:00:00

  • A CX3CR1 genotype associated with retinal vasculitis in patients in the United Kingdom.

    abstract:PURPOSE:To investigate whether polymorphisms in the gene encoding the chemokine receptor CX3CR1, which has been linked to changes in functional ligand-binding activity, are associated with retinal vasculitis (RV) in a cohort of patients in the United Kingdom. METHODS:DNA was prepared from whole blood of 126 patients w...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.05-1631

    authors: Wallace GR,Vaughan RW,Kondeatis E,Mathew R,Chen Y,Graham EM,Stanford MR

    更新日期:2006-07-01 00:00:00

  • Clinical assessment of mirror artifacts in spectral-domain optical coherence tomography.

    abstract::PURPOSE. To investigate the characteristics of a spectral-domain optical coherence tomography (SD-OCT) image phenomenon known as the mirror artifact, calculate its prevalence, analyze potential risk factors, measure severity, and correlate it to spherical equivalent and central visual acuity (VA). METHODS. OCT macular...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.09-4057

    authors: Ho J,Castro DP,Castro LC,Chen Y,Liu J,Mattox C,Krishnan C,Fujimoto JG,Schuman JS,Duker JS

    更新日期:2010-07-01 00:00:00

  • Association of neovascular age-related macular degeneration with specific gene expression patterns in peripheral white blood cells.

    abstract:PURPOSE:Inflammation probably plays a major role in the pathogenesis of age-related macular degeneration (AMD). The authors evaluated whether AMD is associated with gene expression patterns in white blood cells (WBCs) and whether such a pattern may serve as a biomarker for the disease. METHODS:Microarray analysis of g...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-3019

    authors: Lederman M,Weiss A,Chowers I

    更新日期:2010-01-01 00:00:00

  • Intravitreal injection of AAV2 transduces macaque inner retina.

    abstract:PURPOSE:Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized mo...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.10-6250

    authors: Yin L,Greenberg K,Hunter JJ,Dalkara D,Kolstad KD,Masella BD,Wolfe R,Visel M,Stone D,Libby RT,Diloreto D Jr,Schaffer D,Flannery J,Williams DR,Merigan WH

    更新日期:2011-04-25 00:00:00

  • Measuring In Vivo Free Radical Production by the Outer Retina.

    abstract:PURPOSE:Excessive and continuously produced free radicals in the outer retina are implicated in retinal aging and the pathogenesis of sight-threatening retinopathies, yet measuring outer retinal oxidative stress in vivo remains a challenge. Here, we test the hypothesis that continuously produced paramagnetic free radic...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.15-18420

    authors: Berkowitz BA,Bredell BX,Davis C,Samardzija M,Grimm C,Roberts R

    更新日期:2015-12-01 00:00:00

  • A test of a linear model of glaucomatous structure-function loss reveals sources of variability in retinal nerve fiber and visual field measurements.

    abstract:PURPOSE:Retinal nerve fiber (RNFL) thickness and visual field loss data from patients with glaucoma were analyzed in the context of a model, to better understand individual variation in structure versus function. METHODS:Optical coherence tomography (OCT) RNFL thickness and standard automated perimetry (SAP) visual fi...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-2697

    authors: Hood DC,Anderson SC,Wall M,Raza AS,Kardon RH

    更新日期:2009-09-01 00:00:00

  • The spatial and temporal expression of outer segment proteins during development of Macaca monkey cones.

    abstract:PURPOSE:To characterize the spatial and temporal expression of key structural and phototransduction cascade proteins in the monkey cone outer segment (OS). METHODS:Retinas from Macaca monkeys from ages fetal day (Fd) 89 through adulthood were double labeled using immunofluorescence for short (S) or long/medium (L/M) w...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Sears S,Erickson A,Hendrickson A

    更新日期:2000-04-01 00:00:00

  • Transplantation of tissue-engineered epithelial cell sheets after excimer laser photoablation reduces postoperative corneal haze.

    abstract:PURPOSE:To apply tissue-engineered cell sheet transplantation after excimer laser keratectomy as a novel approach for the reduction of postoperative corneal haze. METHODS:Limbal biopsy specimens were obtained, and epithelial cells were cultured on temperature-responsive culture inserts without the use of feeder cells....

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.05-0995

    authors: Hayashida Y,Nishida K,Yamato M,Yang J,Sugiyama H,Watanabe K,Hori Y,Maeda N,Kikuchi A,Okano T,Tano Y

    更新日期:2006-02-01 00:00:00

  • Cone visual cell degeneration in ground squirrel retina: disruption of morphology and cyclic nucleotide metabolism by lodoacetic acid.

    abstract::Photoreceptor degeneration was induced in the cone-dominant retina of the ground squirrel by intracardiac injection of iodoacetic acid. Morphology was examined and cyclic nucleotide levels were determined in retinas taken at various times between 35 min and 11 days after injection. Degenerating cone cells were first d...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Farber DB,Souza DW,Chase DG

    更新日期:1983-09-01 00:00:00

  • Selective interactions of lymphocytes with neonatal and adult lacrimal gland tissues.

    abstract::The lacrimal gland is a functional part of the mucosal immune system and is populated by lymphoid cells that begin to appear early in neonatal development. To define the events controlling the accumulation of these cells, an in vitro adherence assay was used to investigate the interactions of lymphocyte populations wi...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: O'Sullivan NL,Montgomery PC

    更新日期:1990-08-01 00:00:00