Abstract:
PURPOSE:To characterize the spectrum of mutations in the OPA1 gene in a large international panel of patients with autosomal dominant optic atrophy (adOA), to improve understanding of the range of functional deficits attributable to sequence variants in this gene, and to assess any genotype-phenotype correlations. METHODS:All 28 coding exons of OPA1, intron-exon splice sites, 273 bp 5' to exon 1, and two intronic regions with putative function were screened in 94 apparently unrelated white patients of European origin with adOA by single-strand conformational polymorphism (SSCP)-heteroduplex analysis and direct sequencing. Clinical data were collated, and putative mutations were tested for segregation in the respective families by SSCP analysis or direct sequencing and in 100 control chromosomes. Further characterization of selected splice site mutations was performed by RT-PCR of patient leukocyte RNA. Staining of mitochondria in leukocytes of patients and control subjects was undertaken to assess gross differences in morphology and cellular distribution. RESULTS:Twenty different mutations were detected, of which 14 were novel disease mutations (missense, nonsense, deletion-frameshift, and splice site alterations) and six were known mutations. Mutations were found in 44 (47%) of the 94 families included in the study. Ten new polymorphisms in the OPA1 gene were also identified. Mutations occur throughout the gene, with three clusters emerging: in the mitochondrial leader, in the highly conserved guanosine triphosphate (GTP)-binding domain, and in the -COOH terminus. Examination of leukocyte mitochondria from two unrelated patients with splice site mutations in OPA1 revealed no abnormalities of morphology or cellular distribution when compared with control individuals. CONCLUSIONS:This study describes 14 novel mutations in the OPA1 gene in patients with adOA, bringing the total number so far reported to 54. It is likely that many cases of adOA are due to mutations outside the coding region of OPA1 or to large-scale rearrangements. Evaluation of the mutation spectrum indicates more than one pathophysiological mechanism for adOA. Preliminary data suggests that phenotype-genotype correlation is complex, implying a role for other genetic modifying or environmental factors. No evidence was found of pathologic changes in leukocyte mitochondria of patients with adOA.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Thiselton DL,Alexander C,Taanman JW,Brooks S,Rosenberg T,Eiberg H,Andreasson S,Van Regemorter N,Munier FL,Moore AT,Bhattacharya SS,Votruba Mkeywords:
subject
Has Abstractpub_date
2002-06-01 00:00:00pages
1715-24issue
6eissn
0146-0404issn
1552-5783journal_volume
43pub_type
杂志文章,多中心研究abstract:PURPOSE:During mammalian embryonic eyelid closure ADAM17 has been proposed to play a role as a transactivator of epidermal growth factor receptor (EGFR) signaling by shedding membrane bound EGFR ligands. However, ADAM17 also sheds numerous other ligands, thus implicating ADAM17 in additional molecular pathways. The goa...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-11130
更新日期:2013-01-07 00:00:00
abstract:PURPOSE:To evaluate the efficacy of coulomb-controlled iontophoresis (CCI) for delivery of riboflavin prior to corneal collagen cross-linking (CXL). METHODS:The eyes of 20 8-week-old Lewis rats, subject to epithelium-ON (epi-ON, n = 20 eyes) or epithelium-OFF (epi-OFF, n = 20 eyes) conditions, were used to evaluate th...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-13931
更新日期:2014-04-28 00:00:00
abstract:PURPOSE:Trabecular meshwork (TM) cells appear to sense changes in intraocular pressure (IOP) as mechanical stretching. In response, they make homeostatic corrections in the aqueous humor outflow resistance, partially by increasing extracellular matrix (ECM) turnover initiated by the matrix metalloproteinases. To unders...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0075
更新日期:2005-08-01 00:00:00
abstract:PURPOSE:To evaluate the consequences of the expression of a mutant mouse opsin gene on rod- and cone-mediated function. Experimental conditions were chosen to provide a basis of comparison to the results reported for patients with autosomal dominant retinitis pigmentosa (ADRP) in whom the proline at position 23 has bee...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To investigate the accuracy and precision of threshold estimates returned by two Bayesian perimetric strategies, staircase-QUEST or SQ (a Swedish interactive threshold algorithm [SITA]-like strategy) and ZEST (zippy estimation by sequential testing), and to compare these measures with those of the full-threshol...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0023
更新日期:2003-11-01 00:00:00
abstract::The hypotensive effect of ascorbate on intraocular pressure has been reported following topical application, oral administration, or anterior chamber infusion in animals. The present report describes the correlation of aqueous humor ascorbate concentration with intraocular pressure as well as outflow facility in vivo....
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1978-08-01 00:00:00
abstract:PURPOSE:The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose o...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract:Purpose:To determine whether high glucose (HG) or diabetes alters mitochondrial morphology and promotes mitochondrial fragmentation in retinal vascular cells and thereby triggers apoptosis associated with diabetic retinopathy. Methods:To assess whether diabetes promotes mitochondrial fragmentation and thereby triggers...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.10.10
更新日期:2020-08-03 00:00:00
abstract:PURPOSE:Leber congenital amaurosis (LCA) is an inherited retinal disease that causes early-onset severe visual impairment. To evaluate the mutation spectrum in the Chinese population, we performed a mutation screen in 145 Chinese LCA families. METHODS:First, we performed direct Sanger sequencing of 7 LCA disease genes...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-15972
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:Müller cells support retinal neurons with essential functions. Here, we aim to examine the impact of starvation and oxidative stress on glutamate uptake and mitochondrial function in Müller cells. METHODS:Cultured human retinal Müller cells (MIO-M1) were exposed to H2O2 and additional starvation for 24 hours. ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-19275
更新日期:2016-05-01 00:00:00
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
更新日期:2007-05-01 00:00:00
abstract::We use a population balance model to study the mechanism and the rate of centripetal migration of epithelial cells, renewal of the corneal epithelial population by the cell derived from (progeny of) the limbal stem cells and the kinetics of the replacement of the donor corneal epithelium. The epithelial mass is consta...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract:Purpose:Our goal was to generate and characterize a new mouse model in which only angiogenesis- and glaucoma-relevant tissues would be naturally fluorescent. The Matrix Gla (MGP) gene is highly expressed in vascular smooth muscle cells (VSMC) and trabecular meshwork (TM). We sought to direct our Mgp-Cre.KI mouse recomb...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-22992
更新日期:2018-02-01 00:00:00
abstract:PURPOSE:To investigate whether signaling pathways that incorporate protein tyrosine kinases and phosphatases regulate PKC-sensitive, volume-sensitive Cl(-) currents (I(Cl,vol)) in cultured rabbit nonpigmented ciliary epithelial cells. METHODS:Activation of I(Cl,vol) in response to hyposmotic stimulation was recorded w...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
abstract:PURPOSE:We used a rabbit model to evaluate the interface embedded between the recipient corneas and transplanted donor corneal discs after non-Descemet's stripping automated endothelial keratoplasty (nDSAEK). METHODS:Unilateral DSAEK and nDSAEK surgeries were performed on New Zealand white rabbits. In vivo confocal mi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-13544
更新日期:2014-11-18 00:00:00
abstract:PURPOSE:To understand the pathophysiology of human retinal degenerations caused by mutations in the peripherin/RDS gene. METHODS:Three families with autosomal dominant retinal degeneration were found to have mutations in the peripherin/RDS gene. There were two frameshift mutations: a 1-base pair (bp) insertion at codo...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract:PURPOSE:To investigate whether oxygen stresses experienced in retinopathy of prematurity (ROP) trigger signaling through reactive oxygen species (ROS) and whether the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway lead to intravitreous neovascularization (IVNV) in an oxygen-induced ret...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-3256
更新日期:2009-07-01 00:00:00
abstract::Analysis of cell populations in the cornea may be performed rapidly and accurately employing the technique of enzymatic disaggregation. To illustrate this method normal rat corneas and corneas infected 24 and 48 hours previously with Staphylococcus aureus were disaggregated in a solution containing pancreatin and coll...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract:PURPOSE:To investigate the role of the gap junction protein connexin43 (Cx43), which is predominantly expressed in lens epithelial cells in the control of lens development and organization. METHODS:Newborn mice in which the Cx43 gene was disrupted by homologous recombination were used. Lenses from Cx43 (-/-) mice and ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::The authors' study of the viscosities of various concentrations of sodium hyaluronate, chondroitin sulfate, and methylcellulose revealed that sodium hyaluronate and methylcellulose are pseudoplastic fluids in contrast to chondroitin sulfate, which is a Newtonian fluid. Pseudoplastic fluids are ideal for maintaining th...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::PURPOSE. To examine the biomechanical deformation of load bearing structures of the optic nerve head (ONH) resulting from raised intracranial pressure, using high definition optical coherence tomography (HD-OCT). The authors postulate that elevated intracranial pressure induces forces in the retrolaminar subarachnoid ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6782
更新日期:2011-08-22 00:00:00
abstract:Purpose:To assess interocular delays in amblyopes with stereopsis and to evaluate the relationship between interocular delays and the clinical characteristics. Methods:Twenty amblyopes with stereopsis (median, 400 arcseconds) and 20 controls with normal or corrected to normal visual acuity (≤0 logMAR) and normal stere...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.3.22
更新日期:2020-03-09 00:00:00
abstract:PURPOSE:The pharmacokinetics of ophthalmic biotherapeutics are difficult to determine in human vitreous humor. Because of the high transparency of living tissue to near-infrared (NIR) light, the temporal changes in vitreous concentrations of a biomolecule labeled with an NIR fluorescent probe can be monitored in situ w...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-7790
更新日期:2011-09-01 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
abstract:PURPOSE:To correlate retinal histopathology with functional changes caused by the rhodopsin Q64ter mutation. METHODS:A 50-year-old female heterozygote was evaluated clinically and with psychophysical and electroretinographic measurements of rod and cone function. The retinas obtained after death were examined microsco...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract:PURPOSE:Connexin50 (Cx50) is absolutely essential for normal postnatal lens growth. Deletion of Cx50 or replacement with Cx46 by knockin resulted in smaller lenses containing fewer cells. To determine why Cx50-deficient lenses fail to grow normally, cell proliferation was assayed during the period of growth failure. M...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0194
更新日期:2004-09-01 00:00:00
abstract:PURPOSE:The main purpose of this study was to develop a cell culture model of immortalized epithelium from the human cornea for drug permeability testing. METHODS:Immortalized human corneal epithelial (HCE) cells were grown on filters, with various filter materials and coating procedures. In the optimal case, HCE cell...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract:PURPOSE:To determine the distribution of invasive and cytotoxic genotypes among ocular isolates of P. aeruginosa and investigate the influence of the type III secretion system (T3SS) on adhesion to conventional, cosmetic, and silicone hydrogel contact lenses (CL). METHODS:Clinical isolates from 2001 to 2010 were analy...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8184
更新日期:2012-09-21 00:00:00
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:
更新日期:1985-02-01 00:00:00
abstract:PURPOSE:Visual sensations in patients with blindness and retinal degenerations may be restored by electrical stimulation of retinal neurons with implantable microelectrode arrays. A prospective trial was initiated to evaluate the safety and efficacy of a wireless intraocular retinal implant (EPIRET3) in six volunteers ...
journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章
doi:10.1167/iovs.08-2752
更新日期:2009-06-01 00:00:00