Marked alteration of sterol metabolism and composition without compromising retinal development or function.

Abstract:

PURPOSE:To evaluate the consequences of altering retinal sterol metabolism and composition on the development, histologic organization, and electrophysiological function of the retina, under conditions that mimic the biochemical hallmarks of the Smith-Lemli-Opitz (SLO) syndrome. METHODS:Pregnant Sprague-Dawley rats were fed cholesterol-free chow containing AY9944 (treated group), an inhibitor of 3beta-hydroxysterol delta7-reductase, from gestational day 6 through postnatal day (P)28. Control animals were fed the same chow, but without AY9944. In addition, progeny in the treated group were injected subcutaneously every other day from birth to P28 with an olive oil emulsion containing AY9944; control animals received olive oil emulsion alone. At various postnatal times, tissues from treated and control animals were harvested, and their sterol profiles were analyzed by reversed-phase high-performance liquid chromatography. Companion eyes from animals of both groups were examined histologically at P1. At P28, animals were evaluated by electroretinography; tissues were then harvested for biochemical analysis and companion eyes were subjected to histologic and ultrastructural analyses. RESULTS:Treatment of developing rats with AY9944 caused markedly abnormal accumulation of 7-dehydrosterols and severely reduced cholesterol levels in all tissues examined, relative to control animals. Despite this, treated animals exhibited normal retinal development and had no overt ocular defects or decrease in electroretinographic function, up to P28. CONCLUSIONS:These results were unexpected, given the known biophysical effects of such sterol alterations on membrane properties and the profound dysmorphic and cognitive abnormalities associated with genetic defects in 3beta-hydroxysterol delta7-reductase that have been linked to the SLO syndrome. The results suggest that 7-dehydrosterols can substitute functionally for cholesterol in the retina or perhaps can act synergistically with subthreshold levels of residual cholesterol to allow normal cellular structure and function to be achieved.

authors

Fliesler SJ,Richards MJ,Miller C,Peachey NS

keywords:

subject

Has Abstract

pub_date

1999-07-01 00:00:00

pages

1792-801

issue

8

eissn

0146-0404

issn

1552-5783

journal_volume

40

pub_type

杂志文章
  • Decrease of anterior ciliary arterial pressure with increased ocular pressure.

    abstract::The relationship of the ocular pressure to the anterior ciliary arterial pressure was studied by measuring the pressure of the anterior ciliary artery using a modified pressure chamber. Of the 40 subjects, 9 were normal, 16 were ocular hypertensive patients, and 15 were primary, open-angle, glaucoma patients. A signif...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Sakimoto G,Schwartz B

    更新日期:1984-08-01 00:00:00

  • ZO-1: lamellipodial localization in a corneal fibroblast wound model.

    abstract:PURPOSE:To explore the roles of ZO-1 in corneal fibroblasts and myofibroblasts in a model of wounding. METHODS:Antibodies were used to identify ZO-1 in cultured rabbit corneal fibroblasts by immunocytochemistry, Western blot analysis, and immunoprecipitation. For colocalization studies, antibodies to beta-catenin, cad...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.04-0145

    authors: Taliana L,Benezra M,Greenberg RS,Masur SK,Bernstein AM

    更新日期:2005-01-01 00:00:00

  • Assessment of the Retina of Plp-α-Syn Mice as a Model for Studying Synuclein-Dependent Diseases.

    abstract:Purpose:Synucleinopathies such as multiple system atrophy (MSA) and Parkinson's disease are associated with a variety of visual symptoms. Functional and morphological retinal aberrations are therefore supposed to be valuable biomarkers for these neurodegenerative diseases. This study examined the retinal morphology and...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.61.6.12

    authors: Kaehler K,Seitter H,Sandbichler AM,Tschugg B,Obermair GJ,Stefanova N,Koschak A

    更新日期:2020-06-03 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

  • Which method of flicker perimetry is most effective for detection of glaucomatous visual field loss?

    abstract:PURPOSE:The authors compared the efficacy of two different forms of flicker perimetry: temporal modulation perimetry (TMP), which measures contrast thresholds for a fixed temporal frequency, and critical flicker frequency (CFF), which measures the highest frequency for which flicker is detected at a fixed contrast. ME...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Yoshiyama KK,Johnson CA

    更新日期:1997-10-01 00:00:00

  • Purification, molecular cloning, and expression of a novel growth-promoting factor for retinal pigment epithelial cells, REF-1/TFPI-2.

    abstract:PURPOSE:Retinal pigment epithelial (RPE) cells are known to play important roles in maintaining the homeostasis of the retina and in controlling choroidal neovascularization. The purpose of this study was to identify a factor or factors that would stimulate RPE cells to proliferate. METHODS:To isolate such a factor, 1...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.03-0230

    authors: Tanaka Y,Utsumi J,Matsui M,Sudo T,Nakamura N,Mutoh M,Kajita A,Sone S,Kigasawa K,Shibuya M,Reddy VN,Zhang Q,Iwata T

    更新日期:2004-01-01 00:00:00

  • Disease expression in cultured pigment epithelium. Feline mucopolysaccharidosis VI.

    abstract::Primary cultures of retinal pigment epithelial (RPE) cells from cats with mucopolysaccharidosis VI (MPS VI) have been initiated from mixed populations of cells (ie, derived from the entire eyecup and represented by both pigmented and nonpigmented RPE cells). The cells were enzymatically dissociated from the eyecup and...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Stramm L,Haskins M,Desnick RJ,Aguirre G

    更新日期:1985-02-01 00:00:00

  • Association of Upregulated Angiogenic Cytokines With Choroidal Abnormalities in Chronic Central Serous Chorioretinopathy.

    abstract:Purpose:To clarify the distinct molecular pathogenesis of central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV). Methods:Aqueous humor (AH) was collected from 18 acute CSC, 20 chronic CSC, and 20 PNV patients. Concentrations of 30 cytokines in the AH were analyzed using a multiplex bead immunoa...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.18-25517

    authors: Terao N,Koizumi H,Kojima K,Yamagishi T,Nagata K,Kitazawa K,Yamamoto Y,Yoshii K,Hiraga A,Toda M,Kinoshita S,Sotozono C,Hamuro J

    更新日期:2018-12-03 00:00:00

  • Removal of biofilm from contact lens storage cases.

    abstract:PURPOSE:Lens case hygiene practices are important in maintaining safe contact lens wear. However, the effectiveness of various lens case cleaning practices have not been evaluated and compared. This in vitro study aimed to evaluate and compare the efficacy of cleaning practices that are most commonly carried out by len...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.10-5796

    authors: Wu YT,Zhu H,Willcox M,Stapleton F

    更新日期:2010-12-01 00:00:00

  • Objective Ocular Discomfort: Noninvasive Evaluation by Functional Near-Infrared Ray Spectroscopy.

    abstract:Purpose:Patients express their discomfort by subjective complaints, which may not clearly express the extent of their discomfort. This study noninvasively and objectively quantified ocular discomfort, a form of feeling, from the prefrontal cortex by functional near-infrared ray spectroscopy topography. Methods:This ca...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.18-24840

    authors: Ono M,Takano Y,Haida M

    更新日期:2018-09-04 00:00:00

  • Confocal microscopy reveals zones of membrane remodeling in the outer cortex of the human lens.

    abstract:PURPOSE:To optimize fixation, sectioning, and immunolabeling protocols to map the morphology of the human lens with confocal microscopy. METHODS:Transparent human lenses were fixed in 0.75% paraformaldehyde for 24 hours, cut in half, and fixed for another 24 hours. Lenses were cryoprotected, sectioned, and labeled wit...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.09-3435

    authors: Lim JC,Walker KL,Sherwin T,Schey KL,Donaldson PJ

    更新日期:2009-09-01 00:00:00

  • Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo.

    abstract:PURPOSE:To demonstrate the application of multiphoton fluorescence (MF) and second harmonic generation (SHG) microscopy for ex vivo characterization of the structural alterations of human corneas due to keratoconus. METHODS:Buttons of keratoconic corneas derived from penetrating keratoplasty were sent for structural a...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.06-0386

    authors: Tan HY,Sun Y,Lo W,Lin SJ,Hsiao CH,Chen YF,Huang SC,Lin WC,Jee SH,Yu HS,Dong CY

    更新日期:2006-12-01 00:00:00

  • Cone and rod ERG phototransduction parameters in retinitis pigmentosa.

    abstract:PURPOSE:To analyze cone and rod phototransduction parameters from ERG a-waves in patients with RP and to determine the relationships among these parameters, age, and mode of inheritance. METHODS:Sets of four white flashes (3.2-4.4 log scotopic troland [scot td-s]) were presented in the dark. The same stimuli were late...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.02-1104

    authors: Tzekov RT,Locke KG,Hood DC,Birch DG

    更新日期:2003-09-01 00:00:00

  • Visible-Light Optical Coherence Tomography Angiography for Monitoring Laser-Induced Choroidal Neovascularization in Mice.

    abstract:PURPOSE:This study sought to determine the earliest time-point at which evidence of choroidal neovascularization (CNV) could be detected with visible-light optical coherence tomography angiography (vis-OCTA) in a mouse model of laser-induced CNV. METHODS:Visible light-OCTA was used to study laser-induced CNV at differ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.15-18891

    authors: Shah RS,Soetikno BT,Yi J,Liu W,Skondra D,Zhang HF,Fawzi AA

    更新日期:2016-07-01 00:00:00

  • Subconjunctival injections. Preservative-related changes in the corneal endothelium.

    abstract::The morphologic effects on rabbit corneal endothelium of several common ophthalmic vehicle constituents were examined following subconjunctival administration. Profound dose-dependent changes consisting of intercellular vacuolization and thickening of the endothelial layer were noted within 1 day following administrat...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Weinreb RN,Wood I,Tomazzoli L,Alvarado J

    更新日期:1986-04-01 00:00:00

  • Neuroprotectin D1 synthesis and corneal nerve regeneration after experimental surgery and treatment with PEDF plus DHA.

    abstract:PURPOSE:This study was conducted to define whether pigment epithelial-derived growth factor (PEDF), together with docosahexaenoic acid (DHA), enhances the synthesis of neuroprotectin D1 (NPD1) and the regeneration of corneal nerves damaged after surgery. METHODS:Corneal stromal dissection was performed in the left eye...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.09-3641

    authors: Cortina MS,He J,Li N,Bazan NG,Bazan HE

    更新日期:2010-02-01 00:00:00

  • Corneal nerves are necessary for adrenergic reactivation of ocular herpes.

    abstract::Herpes simplex virus type 1 (HSV-1) can infect the cornea and achieve ganglionic latency. HSV-1 can later be activated by a variety of effectors although the exact mechanism of reactivation is unknown. Rabbits harboring latent HSV-1 strain McKrae can be induced to shed virus by ocular iontophoresis of epinephrine to t...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Rootman DS,Haruta Y,Hill JM,Kaufman HE

    更新日期:1988-03-01 00:00:00

  • Incidence of blindness and severe visual impairment in Germany: projections for 2030.

    abstract:PURPOSE:Estimates of the incidences of severe visual impairment and blindness (SVI/B) and their causes are key to good health service planning. Thus, the database of Germany's largest state's blind registry was used to estimate current incidence rates (IR) and to project rates for Germany in 2010 and 2030. METHODS:The...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章,多中心研究

    doi:10.1167/iovs.10-6987

    authors: Finger RP,Fimmers R,Holz FG,Scholl HP

    更新日期:2011-06-21 00:00:00

  • Alkali burn-induced synthesis of inflammatory eicosanoids in rabbit corneal epithelium.

    abstract:PURPOSE:Alkali burning of the rabbit cornea is a well-established model for the study of anterior surface inflammation, neovascularization, and wound-healing processes. 12-hydroxyeicosanoids have been implicated as mediators of such responses. 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE) is a lipoxygenase-derived ar...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Conners MS,Urbano F,Vafeas C,Stoltz RA,Dunn MW,Schwartzman ML

    更新日期:1997-09-01 00:00:00

  • Regulation of matrix metalloproteinase expression by tumor necrosis factor in a murine model of retinal neovascularization.

    abstract:PURPOSE:Hypoxia and growth factors are postulated to be involved in the development of retinal neovascularization through the regulation of extracellular proteinase production. It has been shown that matrix metalloproteinases (MMPs) are elevated in the retina during the neovascularization process. However, the factors ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Majka S,McGuire PG,Das A

    更新日期:2002-01-01 00:00:00

  • Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents.

    abstract::Herpetic stromal disease often is treated with combinations of antiviral agents and corticosteroids. The addition of steroids to the antiviral treatment regimen frequently increases the efficacy of therapy in patients; however, many complications may arise as a result of corticosteroid therapy. Using a rabbit model, t...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: O'Brien WJ,Taylor JL

    更新日期:1991-08-01 00:00:00

  • Intralysosomal iron induces lysosomal membrane permeabilization and cathepsin D-mediated cell death in trabecular meshwork cells exposed to oxidative stress.

    abstract:PURPOSE:To investigate the role of intralysosomal redox-active iron in oxidative stress-induced damage in trabecular meshwork (TM) cells. METHODS:Chronic oxidative stress was applied using the hyperoxic model; acute oxidative stress was applied with H(2)O(2). Microarray analysis was performed using microarrays. mRNA a...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.10-5410

    authors: Lin Y,Epstein DL,Liton PB

    更新日期:2010-12-01 00:00:00

  • Spatial resolution of the tendency-oriented perimetry algorithm.

    abstract:PURPOSE:Tendency-oriented perimetry (TOP) is a new strategy designed to estimate the sensitivity of the visual field quickly, by using linear interpolation between test locations. This study determined the spatial resolution characteristics of TOP. METHODS:A Monte-Carlo technique was used to simulate visual fields, an...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.02-0828

    authors: Anderson AJ

    更新日期:2003-05-01 00:00:00

  • Extracellular nucleotides and interleukin-8 production by ARPE cells: potential role of danger signals in blood-retinal barrier activation.

    abstract:PURPOSE:RPE cell activation is an important feature of autoimmune uveitis. This investigation focused on whether extracellular nucleotides could contribute to this activation, and the effects of ATPgammaS, UTP, and UDP on the production of IL-8 by RPE cells was studied in relation to their expression of functional P2Y ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-1902

    authors: Relvas LJ,Bouffioux C,Marcet B,Communi D,Makhoul M,Horckmans M,Blero D,Bruyns C,Caspers L,Boeynaems JM,Willermain F

    更新日期:2009-03-01 00:00:00

  • Endothelium-dependent regulation of the ophthalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelins.

    abstract:PURPOSE:The endothelium produces nitric oxide and endothelin (ET). This study was designed to investigate the endothelium-dependent regulation of the porcine ophthalmic microcirculation. METHODS:Isolated porcine eyes were perfused with a modified Langendorff setup (Hugo Sachs Elektronik KG, Freiburg, Germany) at a per...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Meyer P,Flammer J,Lüscher TF

    更新日期:1993-12-01 00:00:00

  • Superoxide production by porcine retinal pigment epithelium in vitro.

    abstract::Cultured porcine retinal pigment epithelial cells release superoxide, measured as superoxide dismutase (SOD)-suppressible reduction of cytochrome C, and SOD-suppressible luminol-dependent chemiluminescence. Latex beads stimulated a significant release of superoxide that reached 82 nmol/mg protein in the first 15 min a...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Dorey CK,Khouri GG,Syniuta LA,Curran SA,Weiter JJ

    更新日期:1989-06-01 00:00:00

  • Potential novel mechanism for Axenfeld-Rieger syndrome: deletion of a distant region containing regulatory elements of PITX2.

    abstract:PURPOSE:Mutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease. METHODS:Conserved noncoding elements surrounding PITX2/pitx2 were id...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.10-6060

    authors: Volkmann BA,Zinkevich NS,Mustonen A,Schilter KF,Bosenko DV,Reis LM,Broeckel U,Link BA,Semina EV

    更新日期:2011-03-18 00:00:00

  • Effects of Narrowband Light on Choroidal Thickness and the Pupil.

    abstract:Purpose:To determine the effects of narrowband light exposure on choroidal thickness and the pupil response in humans. Methods:Twenty subjects, ages 21 to 43 years, underwent 1 hour of exposure to broadband, short wavelength "blue," or long wavelength "red" light, or darkness. Choroidal thickness, imaged with spectral...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.61.10.40

    authors: Lou L,Ostrin LA

    更新日期:2020-08-03 00:00:00

  • Reading acuity in children: evaluation and reliability using MNREAD charts.

    abstract:PURPOSE:To study reading acuity in children and assess the reliability of its measurement using the Italian version of the MNREAD reading chart. METHODS:One hundred sixteen children from grades 3 to 8 with normal near vision were tested at a pediatric eye care institution in northeastern Italy. Visual acuity was evalu...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.03-1304

    authors: Virgili G,Cordaro C,Bigoni A,Crovato S,Cecchini P,Menchini U

    更新日期:2004-09-01 00:00:00

  • A functional polymorphism at the FGF10 gene is associated with extreme myopia.

    abstract:PURPOSE:Fibroblast growth factor-10 (FGF10) can modulate extracellular matrix associated genes and, therefore, it could be a myopia susceptibility gene. This study used an animal model, single nucleotide polymorphisms (SNPs) association, and genetic functional assay to evaluate FGF10 gene for myopia. METHODS:The expre...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.13-11814

    authors: Hsi E,Chen KC,Chang WS,Yu ML,Liang CL,Juo SH

    更新日期:2013-05-07 00:00:00