Abstract：
PURPOSE:To evaluate the efficiency, cell specificity, stability, and toxicity of recombinant adeno-associated virus (rAAV)-mediated retinal transduction in vivo in the adult immunocompetent mouse. To assess the usefulness of green fluorescent protein (GFP) for real-time, noninvasive monitoring of retinal transgene expression in vivo. METHODS:Assessment of ocular GFP expression was performed in cohorts of mice for 11 weeks after subretinal injection of a recombinant adeno-associated virus carrying the complementary DNA (cDNA) for GFP. Examinations were performed in vivo by direct observation of fluorescence by ophthalmoscopy, using excitation-barrier filters. Histologic analyses of retinal tissue were used to identify transduced cells and to assess inflammation. RESULTS:Retinal GFP expression can be monitored in vivo using real-time, noninvasive imaging. Recombinant AAV efficiently transduces a variety of cells of the neural retina and of the retinal pigment epithelium (RPE). Transgene expression was not observed until 1 week after infection. The number of GFP-expressing cells increased over 3 weeks, and expressing photoreceptors and RPE, cells persisted at least through 11 weeks (the termination of the experiment). There was no clinical or histologic evidence of inflammatory response. CONCLUSIONS:Retinal gene transfer mediated by rAAV is stable and efficient and is associated with no clinically or histologically detectable toxicity or immune reaction. Green fluorescent protein allows noninvasive assessment of the extent and location of retinal transgene expression as a function of time and promises to be useful alone and as a tag for other transgenes delivered experimentally or therapeutically to the retina.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Bennett J,Duan D,Engelhardt JF,Maguire AMsubject
Has Abstractpub_date
1997-12-01 00:00:00pages
2857-63issue
13eissn
0146-0404issn
1552-5783journal_volume
38pub_type
杂志文章abstract：PURPOSE:To assess the repeatability and interoperator and intersession reproducibility of central corneal thickness (CCT) measurements made by a commercially available optical coherence tomography (OCT) system. METHODS:Intersession and interoperator reproducibility and repeatability were defined according to the guide...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2002-06-01 00:00:00
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
更新日期：2006-12-01 00:00:00
abstract：PURPOSE:Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina. This study aimed to investigate the role of MRP4 in retinal vascular development. METHODS:The r...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-10781
更新日期：2012-12-07 00:00:00
abstract：PURPOSE:Diabetes reduces retinal and visual sensitivity to dim light flashes. However, the impact of diabetes on contrast sensitivity in dim light is unknown. Based on the lowered visual sensitivity previously observed, we hypothesized that contrast sensitivity would similarly be reduced. We therefore examined scotopic...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-10825
更新日期：2013-02-28 00:00:00
abstract：PURPOSE:This study explores the order of assembly of the lens fiber cell plasma membrane. Because the lens must synthesize most of its membrane components, our approach was to map directly the spatial distribution of cholesterol, fatty acid (reflecting phospholipid), and the main intrinsic protein, MP26, synthesis in t...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
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：
更新日期：1997-10-01 00:00:00
abstract：PURPOSE:To describe a method for quantitative mapping of metamorphopsia and abnormalities of oculocentric direction in subjects with epiretinal membranes. METHODS:Binocular correspondence perimetry was performed using red and green dichoptic stimuli applied in a rectangular grid pattern. The study included 9 healthy s...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.04-0952
更新日期：2005-03-01 00:00:00
abstract：PURPOSE:To determine whether retinal progenitor cells in the inner nuclear layer give rise to regenerated cones after laser ablation of photoreceptors in adult goldfish retina. METHODS:Using a technique developed previously in this laboratory, photoreceptors in the retina of adult goldfish were ablated with an argon l...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2001-08-01 00:00:00
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
更新日期：2009-03-01 00:00:00
abstract：PURPOSE:To evaluate the feasibility of introducing exogenous genes and phosphorothioate oligonucleotides into the anterior chamber tissues of rats and monkeys using the authors' fusogenic liposomes. METHODS:Hemagglutinating virus of Japan liposomes containing LacZ DNA-high-mobility group 1 complexes or fluorescein iso...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1998-03-01 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：PURPOSE:Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated with systemic vascular disorders. In addition, clinical studies have implicated that elevated CRP is an independent risk factor for diabetic retinopathy and age-related macular degeneration. However, the direct effect of CRP o...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-1387
更新日期：2008-05-01 00:00:00
abstract：:Tunicamycin (TM), a selective inhibitor of dolichylphosphate-dependent oligosaccharide biosynthesis, effectively blocks glycosylation, but not synthesis, of opsin, the rod visual pigment apoglycoprotein. In parallel with this inhibition, vesicular membrane material accumulates in the compartment between rod inner and ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
abstract：PURPOSE:Mice rendered hypoglycemic by a null mutation in the glucagon receptor gene Gcgr display late-onset retinal degeneration and loss of retinal sensitivity. Acute hyperglycemia induced by dextrose ingestion does not restore their retinal function, which is consistent with irreversible loss of vision. The goal of t...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-8787
更新日期：2012-02-21 00:00:00
abstract：PURPOSE:The influences of diurnal rhythms involving a variety of ocular parameters are implicated in the development of myopia. The purpose of this study was to determine the expression of the melatonin receptor subtype proteins in chick ocular tissues and to examine the role of the circadian signaling molecule melaton...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.05-0195
更新日期：2006-01-01 00:00:00
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
更新日期：2010-02-01 00:00:00
abstract：PURPOSE:Ibuprofen and indomethacin are nonselective prostaglandin synthetase inhibitors that have been shown to improve oxygen-induced retinopathy in mice. Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are potent growth factors involved in retinal development. Th...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-0057
更新日期：2006-07-01 00:00:00
abstract：Purpose:Neuroretinopathy is increasingly being recognized as an independent cause of vision loss in diabetes. Visual field loss, as detected by frequency doubling technology (FDT)-based visual perimetry, is a sign of neuroretinopathy and occurs in early stages of diabetic retinopathy (DR). Here, we hypothesized that FD...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.19-28063
更新日期：2019-11-01 00:00:00
abstract：PURPOSE:To assess the aqueous outflow pathway in primary open-angle glaucoma (POAG) through provocative gonioscopy and channelography with a flexible microcatheter and fluorescein tracer during canaloplasty. METHODS:One eye each was randomly selected from 28 consecutive black African POAG patients undergoing canalopla...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.09-4327
更新日期：2010-03-01 00:00:00
abstract：PURPOSE:To characterize the possible role of transducin Gtβγ-complex in modulating the signaling properties of photoactivated rhodopsin and its lifetime in rod disc membranes and intact rods. METHODS:Rhodopsin photolysis was studied using UV-visible spectroscopy and rapid scanning spectroscopy in the presence of hydro...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-9350
更新日期：2012-03-09 00:00:00
abstract：PURPOSE:To investigate the role of Toll-like receptors (TLRs) 2, 3, 4, and 8 in the pathogenesis of Behcet's disease (BD). METHODS:Sixteen patients with active ocular BD and 16 healthy volunteers were included in this study. Total RNA was isolated from PBMCs to determine mRNA levels of TLRs, including TLR2, TLR3, TLR4...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.13-12159
更新日期：2013-09-05 00:00:00
abstract：PURPOSE:The aim of this study was to elucidate the molecular mechanisms that lead to a dominant nuclear cataract in a mouse harboring the Y118D mutation in the alphaA-crystallin gene. METHODS:The physicochemical properties of alpha-crystallin obtained from mouse lenses with the Y118D mutation as well as a recombinant ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.08-3070
更新日期：2009-06-01 00:00:00
abstract：PURPOSE:To determine global mRNA expression levels in corneal and conjunctival epithelia and identify transcripts that exhibit preferential tissue expression. METHODS:cDNA samples derived from human conjunctival and corneal epithelia were hybridized in three independent experiments to a commercial oligonucleotide arra...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-0998
更新日期：2007-05-01 00:00:00
abstract：:Specimens for chlamydial isolation culture and direct fluorescent antibody cytology (DFA) were collected from 1671 women and children from a trachoma-endemic area in Central Tanzania. Trachoma was graded using the new World Health Organization grading scheme, and 54% of the children and 9% of the women had inflammator...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1989-08-01 00:00:00
abstract：PURPOSE:Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are genetically heterogeneous, with 11 genes currently implicated. The LCA chip may be used to interrogate many variants in one hybridization reaction. The purpose of this study was to assess the utility of this technology. METHO...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-0207
更新日期：2007-12-01 00:00:00
abstract：PURPOSE:Bacillus cereus causes one of the most rapidly blinding forms of bacterial endophthalmitis. Migration of B. cereus throughout the eye during endophthalmitis is a unique aspect of this disease that may contribute to intraocular virulence. This study was conducted to analyze the contribution of swarming and intra...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-0301
更新日期：2006-10-01 00:00:00
abstract：PURPOSE:Visibility of low-spatial frequency stimuli improves when their contrast is modulated at 5 to 10 Hz compared with stationary stimuli. Therefore, temporal modulations of visual objects could enhance the performance of low vision patients who primarily perceive images of low-spatial frequency content. We investig...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-9157
更新日期：2012-09-06 00:00:00
abstract：PURPOSE:Drusen are risk factors for age-related macular degeneration and have been shown to negatively impact cells of the RPE and retina. In this study, the effects of drusen on the synaptic machinery of retinal photoreceptors are investigated. METHODS:Human donor eye tissue containing retina, RPE, and choroid was pr...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.05-0767
更新日期：2005-12-01 00:00:00
abstract：PURPOSE:To reconstruct the role played by vascular endothelium in the elevation of circulating von Willebrand factor (vWf) in diabetic patients with microangiopathy and, specifically, to determine whether storage and synthesis of vWf is altered in diabetic retinal vessels. METHODS:Trypsin digests were prepared from re...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:Selenium toxicity was investigated in cultured rabbit lenses to provide further information about the role of Ca++ in Se cataract. At a dose of 0.1 mM for 20 hr, Se induces a 10% change in Na levels within 6 hr, a 30% increase after 20 hr, and a three-fold increase within 48 hr of subsequent culture after removal of S...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
