Abstract：
PURPOSE:To investigate functional interactions between the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and the nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant system in cultured human retinal pigment epithelium (RPE) cells. METHODS:Cultured ARPE-19 cells were treated with different concentrations of PI3K inhibitors, followed by exposure to sulforaphane, an Nrf2 inducer. Akt phosphorylation was detected by Western blot analysis. Intracellular glutathione (GSH) content was measured by HPLC. Expression of genes downstream of Nrf2, including glutamate-cysteine ligase (GCL) and glutathione S-transferase, was measured by quantitative RT-PCR. Nrf2 activity was measured by a dual luciferase assay after transfection of a reporter plasmid containing the antioxidant response element (ARE). The small interference RNA approach was used to knock down Nrf2 in the RPE. Nrf2 localization was determined by subcellular fractionation and Western blot analyses. RESULTS:PI3K inhibitors wortmannin and LY294002 caused dose-dependent cellular and mitochondrial GSH depletion and downregulation of the modulatory subunit of GCL in cultured RPE cells. Both the basal and the induced Nrf2 activities were inhibited by wortmannin and LY294002. Overexpression of a constitutively active form of Akt potentiated Nrf2 activation, and the effect of Akt was blocked by siRNA that knocked down Nrf2. LY294002 also inhibited sulforaphane-induced Nrf2 nuclear translocation. CONCLUSIONS:The PI3K/Akt pathway plays key roles in regulating Nrf2-ARE-dependent protection against oxidative stress in the RPE.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Wang L,Chen Y,Sternberg P,Cai Jdoi
10.1167/iovs.07-1099subject
Has Abstractpub_date
2008-04-01 00:00:00pages
1671-8issue
4eissn
0146-0404issn
1552-5783pii
49/4/1671journal_volume
49pub_type
杂志文章abstract：:Steady-state visual evoked potentials were elicited by the appearance/disappearance of sinusoidal gratings of varying spatial frequency for both eyes of amblyopic subjects. The amblyopic eyes showed reduced responses and a phase shift relative to the nonamblyopic eyes across a wide range of spatial frequencies. Both t...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1978-06-01 00:00:00
abstract：PURPOSE:To determine the distribution of perceived visual ability for functional vision performance among persons with low vision in the Indian state of Andhra Pradesh. METHODS:As part of a population-based epidemiologic study, the Andhra Pradesh Eye Disease Study (APEDS), a 16-item visual function questionnaire was d...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.04-0243
更新日期：2004-10-01 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 determine the efficacy of a new formulation of topical dexamethasone 0.1%/povidone-iodine 0.4% (FST-100) in reducing clinical symptoms and infectious viral titers in a rabbit model of adenoviral keratoconjunctivitis. METHODS:Rabbit corneas were inoculated bilaterally with 2×10(6) plaque-forming-units (PFU) ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.10-5944
更新日期：2011-01-21 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：Purpose:To give a European regulatory overview of the requirements on and the use of biomarkers or surrogate endpoints in the development of drugs for ocular disease. Methods:Definitions, methods to validate new markers, and circumstances where surrogate endpoints can be appropriate are summarized. Results:The key en...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章,评审
doi：10.1167/iovs.17-21778
更新日期：2017-05-01 00:00:00
abstract：PURPOSE:Genetic modification of cells before transplantation may allow the delivery of neuroprotective and other functional molecules to patients with neurodegenerative diseases. To avoid complications associated with virally transfected cells, we have explored the use of nonviral methods to insert genetic material int...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.10-6178
更新日期：2011-07-23 00:00:00
abstract：Purpose:Effective intravitreal gene delivery to cells of the central retina (i.e., photoreceptors) would be of substantial benefit for treating patients with retinal diseases, such as achromatopsia, where retinal detachment from a subretinal may be harmful. Previous studies demonstrated that mutation of the recombinant...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.17-22281
更新日期：2017-12-01 00:00:00
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 includi...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.15-17629
更新日期：2015-12-01 00:00:00
abstract：PURPOSE:Although the presence of IgG autoantibodies in the vitreous of spontaneous cases of equine recurrent uveitis (ERU) has been demonstrated, the potential role of IgM reactivities during ERU pathogenesis remains unexplored. The purpose of this study was to examine the presence of IgM autoantibodies in vitreous spe...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-8734
更新日期：2012-01-25 00:00:00
abstract：PURPOSE:To determine the effects of X-linked and autosomal recessive Alport syndrome on retinal basement membranes and how these result in the characteristic perimacular dot-and-fleck retinopathy, lozenge, and macular hole. METHODS:The type IV collagen chains present in the normal retina were determined immunohistoche...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章,多中心研究
doi：10.1167/iovs.08-3323
更新日期：2010-03-01 00:00:00
abstract：PURPOSE:To determine if cataract surgery on eyes with AMD confers as much functional visual improvement as surgery on eyes without retinal pathology. METHODS:This is a retrospective analysis of 4924 cataract surgeries from the Veterans Healthcare Administration Ophthalmic Surgical Outcomes Data Project (OSOD). We incl...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.14-16069
更新日期：2015-04-01 00:00:00
abstract：PURPOSE:To study the distribution and predominant orientations of fibrillar collagen at different depths throughout the entire thickness of the human cornea. This information will form the basis of a full three-dimensional reconstruction of the preferred orientations of corneal lamellae. METHODS:Femtosecond laser tech...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.09-3669
更新日期：2009-11-01 00:00:00
abstract：Purpose:Corneal endothelial cells (CECs) are critical in maintaining clarity of the cornea. This study was initiated to develop peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem cell (iPSC)-derived CECs. Methods:We isolated PBMCs and programmed the mononuclear cells to generate iPSCs, which...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.17-22927
更新日期：2018-05-01 00:00:00
abstract：PURPOSE:To assess the mutation spectrum in the ABCR gene and clinical phenotypes in Italian families with autosomal recessive Stargardt disease (STGD1) and fundus flavimaculatus (FFM). METHODS:Eleven families from southern Italy, including 18 patients with diagnoses of STGD1, were clinically examined. Ophthalmologic e...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：PURPOSE:Adeno-associated viral (AAV) vectors have been used to express several different proteins in the eye. The purpose of this study was to determine whether AAV-mediated intraocular gene transfer of pigment epithelium-derived factor (PEDF) inhibits the development of choroidal neovascularization (CNV) in a murine m...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2002-06-01 00:00:00
abstract：:The authors created a new rabbit model for keratoconjunctivitis sicca by cauterizing the lacrimal gland excretory duct and surgically removing the nictitating membrane and harderian gland. Although the slit-lamp examination findings remained normal for the first 8 wk postoperatively, tear-film osmolarity was elevated ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
abstract：PURPOSE:To quantify the spatial and temporal nature of congenital periodic alternating nystagmus (PAN) and to test the hypothesis that PAN results from a temporal shift in the null zone. METHODS:Twenty-five subjects with oculocutaneous albinism (16 tyrosinase negative and 9 tyrosinase positive) and 7 with ocular albin...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：PURPOSE:To identify genes and molecular mechanisms associated with photoreceptor degeneration in a canine model of XLRP caused by an RPGR exon ORF15 microdeletion. Methods. Expression profiles of mutant and normal retinas were compared by using canine retinal custom cDNA microarrays. qRT-PCR, Western blot analysis, and...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.10-5443
更新日期：2010-11-01 00:00:00
abstract：UNLABELLED:PURPOSE. Test the hypothesis that the developmental increases in rod photoreceptor sensitivity and rod-mediated visual sensitivity at 10 degrees, 20 degrees , and 30 degrees eccentric are concurrent. It is known that maturation of the parafoveal (10 degrees eccentric) rod outer segments and visual sensitivit...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
abstract：:A method of analysing fluorescein angiograms that yields a parameter of intraocular blood flow designated as the fluorescein appearance rate is presented. The appearance rate was decreased in those eyes in which intraocular pressure (Pi) was found to be increased. The appearance rate was also decreased in the two case...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：PURPOSE:Pterygia are a common, benign, fibrovascular, and infiltrative process of the corneal-conjunctival junction of unknown pathogenesis. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes active against all components of the extracellular matrix, whose activity is specifically neutralized by tissu...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：PURPOSE:To investigate possible protective effects of lens epithelium-derived growth factor (LEDGF) against photoreceptor death in light-damaged, Royal College of Surgeons (RCS) and P23H rhodopsin transgenic rats. METHODS:Twelve-week-old Sprague-Dawley (SD), 6-week-old RCS, and 10-day-old P23H (line 1, heterozygote) r...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：PURPOSE:To study the effect of aminoguanidine (AMG), an inhibitor of nitric oxide production, on the ocular infection of Balb/c mice with herpes simplex virus (HSV) type 1 strain F and HSV-2 strain G. METHODS:Animals were treated with different amounts of AMG (0.5, 0.1, and 0.05 mg/mouse) by topical application in the...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:The circulating renin-angiotensin system (RAS) is an important determinant in maintaining adequate systemic blood pressure, and it also may modify organ-specific blood flow. All recognized RAS components have been identified in the eye. In this study, angiotensinogen (ANG) was localized using an affinity-purified anti...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
abstract：PURPOSE:To investigate the effect of nerve growth factor (NGF) in combination with docosahexaenoic acid (DHA) on corneal nerve regeneration in a rabbit model after PRK and correlate the findings with functional tear test. METHODS:Unilateral PRK was performed on 21 New Zealand albino rabbits. Three groups, each consist...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.05-0241
更新日期：2005-09-01 00:00:00
abstract：PURPOSE:The authors' previous study showed that the expression of a Rho-associated serine/threonine kinase (ROCK) is regulated during cell cycle progression in corneal epithelial cells. The present study was conducted to determine whether and how Rho/ROCK signaling regulates cell cycle progression. METHODS:Rabbit corn...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-0488
更新日期：2008-01-01 00:00:00
abstract：:Two distinct patterns of delayed-onset, cell-mediated hypersensitivity have been induced in the guinea pig eye with the same soluble protein antigen and two different methods of immunization. The predominant histologic feature of these reactions was the large number of eosinophils which infiltrated the uveal tract and...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1978-04-01 00:00:00
abstract：:Dopamine, cis-flupenthixol, and dibutyryl cAMP affected the standing potential and light-evoked responses of the perfused cat eye in vitro. At micromolar concentrations, dopamine, a retinal neurotransmitter, increased the standing potential of the eye. At slightly higher concentrations, dopamine abolished the "light p...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：PURPOSE:The influence of genetic and prenatal environmental factors on characteristics of saccadic performance were evaluated in young monozygotic (MZ) twins (8-19 years old) of known chorion type. METHODS:Saccadic eye movements were recorded using an infrared system. Saccadic latency, accuracy, and parameters of ampl...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
