Abstract:
PURPOSE:To investigate the effect of ABCA4 mutation status on lipofuscin-related quantitative autofluorescence (qAF) in humans and on bisretinoid accumulation in mice. METHODS:Genotyped parents (n = 26; age 37-64 years) of patients with biallelic ABCA4-related retinopathy underwent in-depth retinal phenotyping including qAF imaging as a surrogate measure for RPE lipofuscin accumulation. In addition, bisretinoids as the main components of autofluorescent lipofuscin at the ocular fundus were quantified in Abca4-/-, Abca4+/-, and wild-type mice. RESULTS:Index patients showed a retinal phenotype characteristic for ABCA4-related retinopathy, including increased qAF levels. In contrast, qAF measures in carriers of only one ABCA4 mutation were not different from age-matched controls in this sample, and there was no difference between truncating and missense mutations. Also, none of these carriers presented an abnormal phenotype on conventional imaging. One parent with ABCA4-related retinopathy and increased qAF carried an additional ABCA4 mutation, explaining the phenotype under a recessive disease model (pseudodominance). Biochemical analysis in the mouse model revealed direct downstream products (A2PE-H2, at-RALdimer-PE) of the ABCA4 substrate N-Ret-PE to be similar in wild-type and Abca4+/- mice. Both bisretinoids were 12- to 18-fold increased in Abca4-/- mice. Levels of A2E and A2PE in Abca4+/- mice were in between those measured in wild-type and Abca4-/- mice. CONCLUSIONS:This study indicates that carriers of monoallelic ABCA4 mutations are phenotypically normal. However, biochemical analysis in the Abca4-deficient mouse model suggests detectable effects of one mutation in ABCA4 on the molecular level. The findings may have implications for therapeutic approaches such as gene replacement therapy.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Müller PL,Gliem M,Mangold E,Bolz HJ,Finger RP,McGuinness M,Betz C,Jiang Z,Weber BH,MacLaren RE,Holz FG,Radu RA,Charbel Issa Pdoi
10.1167/iovs.15-17629subject
Has Abstractpub_date
2015-12-01 00:00:00pages
8179-86issue
13eissn
0146-0404issn
1552-5783pii
2479482journal_volume
56pub_type
杂志文章abstract:PURPOSE:To determine the relationship between changes in contrast sensitivity, if any, after glaucoma therapy and the test-retest reliability of the CSV-1000 contrast sensitivity test. METHODS:Patients with primary open angle glaucoma (N = 16) were retrospectively evaluated to determine changes in visual function, as ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The purpose of the current study was to investigate the relationship between systemic blood pressure (BP) and long posterior ciliary arterial (LPCA) blood flow (BF) in response to autonomic drugs, and to determine the types of receptors involved. LPCA BF was measured in anesthetized rabbits at the retrobulbar region u...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract:PURPOSE:By their control of membrane potential and intracellular free Ca(2+) ([Ca(2+)](i)), K(+) currents are pivotal in the regulation of arterial smooth muscle tone. The goal of the present study was to identify and characterize the A-type K(+) current in retinal microvascular smooth muscle (MVSM) and to examine its ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-1465
更新日期:2005-09-01 00:00:00
abstract:PURPOSE:To characterize the expression patterns of myosin heavy chain (MyHC) isoforms in mouse extraocular muscles (EOMs) during postnatal development. METHODS:MyHC isoform expression in mouse EOMs from postnatal day (P)0 to 3 months was evaluated by quantitative polymerase chair reaction (qPCR) and immunohistochemist...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5937
更新日期:2010-12-01 00:00:00
abstract::The vestibulo-ocular reflex of normal monkeys was tested by a modified Bárány spinning test (B-test) and by sinosoidal rotation. The two tests gave concordant estimates of the time constant and corner frequency. Deviation from concordance was caused largely by modification of the reflex during the testing procedures. ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1979-10-01 00:00:00
abstract::N-formimidoyl thienamycin (MK-787) is a new beta-lactam with potent activity against both aerobic and anaerobic gram-positive and gram-negative bacteria. Its spectrum and activity suggest it may be useful in treatment of complicated intraocular infections. Its ocular penetration was studied in New Zealand white rabbit...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-08-01 00:00:00
abstract:PURPOSE:To determine whether a new cyclic GMP analog, 2'-O-(4-benzoyl)benzoylguanosine 3',5' cyclic monophosphate (BB-cGMP), significantly reduces intraocular pressure in either normotensive or hypertensive eyes of rabbits. METHODS:Intraocular pressure of normal adult rabbits and/or rabbits with alpha-chymotrypsin-ind...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract:PURPOSE:To study possible causes of motility disturbances that may result from orbital decompression surgery in patients with Graves orbitopathy and especially the role of rectus extraocular muscle paths. METHODS:Sixteen patients with Graves orbitopathy were studied before and 3 to 6 months after translid (6 patients)...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4108
更新日期:2010-09-01 00:00:00
abstract:PURPOSE:To assess the range of macular pigment optical density (MPOD) in a healthy group of young adults of South Asian origin; to investigate whether any dietary factors or personal characteristics were related to intersubject variations in MPOD; and to compare the mean MPOD of the South Asian group with the mean MPOD...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-10957
更新日期:2013-04-17 00:00:00
abstract:PURPOSE:Linkage intervals for erosive vitreoretinopathy (ERVR) and Wagner disease previously were found to overlap at 5q14.3. In a Japanese family with Wagner disease, a CSPG2/Versican splice site mutation (c.4004-2A-->G) was recently reported that resulted in a 39-nucleotide exon 8 in-frame deletion. We investigated w...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0141
更新日期:2006-08-01 00:00:00
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
更新日期:2014-02-12 00:00:00
abstract::Recent work demonstrated that a mannose receptor is involved in the phagocytosis of rod outer segments by the rat retinal pigment epithelium (RPE). In this study the binding of soluble mannose-containing ligands by human RPE explants is described. In addition, the authors report the isolation of a mannose receptor fro...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract:PURPOSE:The RAS association domain family 1 (RASSF1) gene is a tumor-suppressor gene located on chromosome 3p21.3. The alternative transcript (RASSF1a) has been shown to be inactivated by hypermethylation in several human malignancies, including breast, prostate, and lung cancer, and in cutaneous melanoma. The purpose ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0781
更新日期:2007-02-01 00:00:00
abstract:PURPOSE:7-Ketocholesterol is a highly toxic oxysterol found in abundance in atherosclerotic plaques and is believed to play a critical role in atherosclerosis. The purpose of this study was to identify and localize 7-ketocholesterol (7kCh) in the primate retina and to examine the potential consequences of its presence ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-2373
更新日期:2009-02-01 00:00:00
abstract::PURPOSE. To investigate morphologic photoreceptor layer abnormalities and their correlation with visual function in occult macular dystrophy (OMD), by using spectral-domain optical coherence tomography (SD-OCT). METHODS. This observational case series included 18 eyes of 9 patients with OMD. All patients underwent an ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4169
更新日期:2010-07-01 00:00:00
abstract::In previous studies we found that a mild thermal burn of the vitamin A-deficient rat cornea caused collagenase release into the medium of corneas placed in culture media 72 hr after applying the burn. Collagenase was released only on day 1 of culture and was not released from identically burned corneas of control rats...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:Retinal blood vessel diameter and arteriovenous ratio (AVR) are commonly used diagnostic parameters. Because vascular walls are typically not visible in funduscopy, clinical AVR estimation is based on the lumen rather than the entire vessel diameter. Here the authors used a transgenic mouse model to quantify AV...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-5139
更新日期:2010-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-10816
更新日期:2013-06-04 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.18-25085
更新日期:2018-09-04 00:00:00
abstract::Topical commercial phenylephrine HCl (Neo-Synephrine 10%) has been shown to cause an increase in corneal thickness and reversible vacuolization of corneal endothelial cells in rabbits. Using an in vivo model of regenerated corneal endothelial cells in the cat, we compared the cytotoxicity of phenylephrine-HCl 10% to r...
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:The aim of this study was to analyze lymphocyte infiltration using immunohistochemistry in proliferative diabetic retinopathy (PDR) membranes. METHODS:Sixteen patients, 13 with PDR and 3 without diabetes, underwent pars plana vitrectomy, and the epiretinal membrane was peeled. Formalin-fixed, paraffin-embedded...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-3767
更新日期:2009-12-01 00:00:00
abstract:PURPOSE:To examine the expression of integrin vitronectin receptors (integrins alphavbeta3 and alphavbeta5) in native human fetal retinal pigment epithelium (RPE) and cultured hunman fetal RPE and to examine the role of RPE VnRs in the phagocytosis of photoreceptor rod outer segments (ROS). METHODS:Monoclonal antibodi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::A single injection of an aqueous suspension of group A streptococcal peptidoglycan-polysaccharide complexes (PG-PS) when injected intraperitoneally into Lewis rats induced a self-limiting bilateral uveitis with associated perpetuating polyarthritis. The uveitis was characterized clinically during the first 72 h by iri...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract:Purpose:To investigate the relationship between lens power and age as well as the relationship between lens power and axial length (AL) in Chinese children and adolescents. Methods:The participants underwent a comprehensive ophthalmic examination that included AL, cycloplegic refraction, and Pentacam measurements. The...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-22639
更新日期:2017-11-01 00:00:00
abstract:PURPOSE:Achieving good vision in infants born with a unilateral cataract is believed to require early surgery and consistent occlusion of the fellow eye. This article examines the relationship between adherence to patching and grating acuity. METHODS:Data came from the Infant Aphakia Treatment Study, a randomized clin...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1167/iovs.11-8457
更新日期:2012-06-05 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-15474
更新日期:2015-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1034
更新日期:2006-04-01 00:00:00
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:
更新日期:1990-08-01 00:00:00