Abstract：
PURPOSE:Inhibiting mechanistic target of rapamycin (mTOR) by pharmacological or genetic approaches can extend lifespan in mammals. The kinase activity of mTOR is controlled by upstream regulatory proteins and its subcellular localization. The purpose of this study was to characterize age-related alterations and functional consequences of mTOR signaling in the postmitotic RPE cells. METHODS:Activity of mTOR complex 1 (mTORC1) was monitored by measuring phosphorylation status of its downstream effector protein S6, in either cultured human RPE cells or RPE explants prepared from mice at different ages. Subcellular distribution of mTOR was investigated by immunofluorescent staining of RPE culture or flatmount. The signaling of mTORC1 was modulated by either overexpression of a small guanosine triphosphatase, Ras homolog enriched in brain (Rheb), or disruption of the Ragulator complex with small interference RNA targeting p18. The effects of mTOR pathway on degradation of phagocytosed photoreceptor outer segments (POS) were determined by measuring the turnover rate of rhodopsin. RESULTS:Aged RPE cells had more lysosome-associated mTOR and had increased response to amino acid stimulation. The lysosome distribution was essential for mTORC1 function, as disruption of the Ragulator complex abolished mTORC1 activation by amino acids. Increased mTORC1 activity caused decreased rate of degradation of internalized POS in the RPE. CONCLUSIONS:Aging changes the subcellular localization and function of mTOR in the RPE. Increased mTORC1 inhibits POS degradation and may further exacerbate lysosome dysfunction of aged RPE.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Yu B,Xu P,Zhao Z,Cai J,Sternberg P,Chen Ydoi
10.1167/iovs.14-14758subject
Has Abstractpub_date
2014-12-09 00:00:00pages
8638-50issue
12eissn
0146-0404issn
1552-5783pii
iovs.14-14758journal_volume
55pub_type
杂志文章abstract：PURPOSE:The S1 RNA binding domain 1 (SRBD1) and elongation of long-chain fatty acids family member 5 (ELOVL5) have been reported to be susceptibility genes for early-onset normal-tension glaucoma (NTG). The present study we conducted to assess whether these genes were associated with primary open-angle glaucoma (POAG),...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章,多中心研究
doi：10.1167/iovs.11-7382
更新日期：2011-06-28 00:00:00
abstract：:The impact of aging on cell loss in the human retina was examined in foveal and temporal equatorial regions in eyes from 35 donors with ages spanning a 78-yr period from the second to the ninth decade of life. Equatorial cones and retinal pigment epithelial cells (RPE) decreased at uniform rates from the second to the...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:Light reflected from 50 micrometer diameter spots on the fundi of two adult rhesus monkeys was measured as a function of wavelength in 10 nm jumps from 400 to 900 nm. The areas measured were a retinal artery and vein, areas of the disk, macula, and retina devoid of visible blood vessels, and the foveola. The eyes of 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 calculate the relative amount of hemoglobin (Hb) in sectors of the optic nerve head (ONH) from stereoscopic color fundus images using the Laguna ONhE method and compare the results with the visual field evaluation and optical coherence tomography (OCT). METHODS:Healthy eyes (n = 87) and glaucoma eyes (n = 7...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.14-15592
更新日期：2015-02-10 00:00:00
abstract：PURPOSE:Methylprednisolone (MP) is commonly used to treat traumatic optic neuropathy and optic neuritis, but its benefit in terms of neuronal survival remains controversial. The aim of this study was to investigate the effects of MP on retinal ganglion cell (RGC) survival and visual function after ischemia in rats. ME...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.08-1869
更新日期：2008-11-01 00:00:00
abstract：PURPOSE:Mucosa-associated lymphoid tissue (MALT) represents a part of the immune system located at mucosal surfaces. Its presence in the human eye is the point in question in the current study. Its occurrence, components, topography, and probable functional significance in the human conjunctiva and lacrimal drainage sy...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
abstract：PURPOSE:To evaluate the effects of 5-fluorouracil (5-FU) on ocular cells in vitro and the effects of degradable 5-FU-loaded poly(DL-lactide-co-glycolide; PDLGA) 50:50 implant in the rabbit eye in vivo. METHODS:Cytotoxicity was assessed with a tetrazolium salt WST-1 cell proliferation/viability test and a lactate dehyd...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.08-3016
更新日期：2009-05-01 00:00:00
abstract：:Monkeys eyes were fixed with glutaraldehyde in vivo at positive intraocular pressure of 35 or 25 mm Hg and compared with eyes fixed without a positive pressure gradient, with the use of light microscopy and transmission and scanning electron microscopy. The entire endothelial lining of the inner wall of Schlemm's cana...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1979-01-01 00:00:00
abstract：PURPOSE:This study observed biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus in contact lens cases and investigated the inhibitory effects of 2,2'-dipyridyl (2DP) and 1,2,3,4,6-penta-O-galloyl-b-D-glucopyranose (PGG). METHODS:Biofilm formation of P. aeruginosa ATCC 9027 and S. aureus ATCC 25923 an...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.15-17723
更新日期：2015-11-01 00:00:00
abstract：PURPOSE:To investigate whether visual deficits in children with infantile spasm (IS) are the result of seizure activity or of treatment with the anticonvulsant drug vigabatrin (VGB). METHODS:Vision function was determined in three experiments by determining peak contrast sensitivity (CS) and grating acuity (GA) with t...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-0755
更新日期：2007-08-01 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:To describe the clinical findings and to identify the genetic locus in a Dutch family with autosomal dominant benign concentric annular macular dystrophy (BCAMD). METHODS:All family members underwent ophthalmic examination. Linkage analysis of candidate retinal dystrophy loci and a whole genome scan were perfo...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.03-0392
更新日期：2004-01-01 00:00:00
abstract：PURPOSE:In situ 2-photon excitation fluorescence (TPEF) of the human trabecular meshwork (TM) reveals beams of heterogeneous autofluorescence (AF) comprising high intensity fluorescent fibers (AF-high) on a background of lower intensity fluorescence (AF-low). To determine the sources of this AF heterogeneity, we imaged...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-11235
更新日期：2013-07-18 00:00:00
abstract：:Vitrectomy has been shown to halt diabetic retinal neovascularization, but the mechanism of this process is unknown. We propose that vitrectomy improves the oxygen supply to ischemic inner retina by way of fluid currents in the vitreous cavity. In order to test this hypothesis, we induced branch retinal vein occlusion...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:A pattern electroretinogram (PERG) can be recorded when the eye wearing the electrode is occluded and the stimulus is viewed with the other eye. We find that this phenomenon occurs when an Arden gold foil electrode is used, but not when either an ERG-Jet lens or a scleral lens electrode is used. Therefore, a corneal-t...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
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journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：PURPOSE:To determine whether the intact isolated ciliary epithelial bilayer retains the alpha-2 and beta adrenergic receptor activation and interaction described for whole ciliary processes and whether this pure epithelial bilayer displays bioelectric parameters sensitive to alterations in cyclic adenosine Monophosphat...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：PURPOSE:To study in an infant rat model of retinopathy of prematurity, the rod photoreceptors, which are known to have attenuated photoresponses. METHODS:Rhodopsin was extracted from whole retinas, the thickness of the rod outer segment (ROS) layer was measured, large phagosomes were counted, and the ROS ultrastructur...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：PURPOSE:To document the cyclovertical ocular motor mechanism used for vertical fusion in healthy subjects, and to explore whether vertical vergence training in healthy individuals can produce objectively confirmed vertical deviations that change with head tilt, revealing a basic mechanism that can produce a pattern of ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-11368
更新日期：2013-05-03 00:00:00
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journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：PURPOSE:Activity in regions of the visual cortex corresponding to central scotomas in subjects with macular degeneration (MD) is considered evidence for functional reorganization in the brain. Three unresolved issues related to cortical activity in subjects with MD were addressed: Is the cortical response to stimuli pr...
journal_title：Investigative ophthalmology & visual science
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doi：10.1167/iovs.09-4926
更新日期：2010-12-01 00:00:00
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journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.03-0845
更新日期：2004-06-01 00:00:00
abstract：PURPOSE:To study relationships between glaucoma-sensitive components identified with frequency-domain analysis of global-flash multifocal electroretinogram (mfERG), regional retinal nerve fiber layer thickness (RNFLT), and local visual field sensitivity (VS). METHODS:Eleven macaque monkeys, including four controls and...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.10-6667
更新日期：2011-06-01 00:00:00
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
更新日期：2004-09-01 00:00:00
abstract：PURPOSE:The association of age and blood pressure (BP) with retinal vessel change is widely reported, with inverse relationships between retinal arteriolar and venular diameter and increasing age and elevated BP. No previous studies have dissected the separate effects of age and BP on the diameter of retinal vessels. ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-0893
更新日期：2007-02-01 00:00:00
abstract：PURPOSE:To identify cell types and extracellular matrix components in Molteno implant capsules. METHODS:Histologic features including cytology, distribution of apoptotic cells, cytoantigens, collagens, basement membranes, elastic fibers, and glycoproteins were examined by light microscopy. Findings were correlated wit...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-1424
更新日期：2009-03-01 00:00:00
abstract：:To investigate the pathogenesis of ocular cytomegalovirus infections, 3-week-old BALB/c mice were inoculated with 10(4) plaque-forming units of murine cytomegalovirus (MCMV) by the right anterior chamber and studied sequentially with the use of virus assays and in situ nucleic acid hybridization methods. During acute ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：PURPOSE:Myopia is a common complex trait that affects up to 60% of some populations. Its development is influenced by multiple genes and environmental factors. PAX6 and SOX2 are genes with fundamental roles in ocular growth and development, and they have been linked with myopia in a recent linkage study. The authors in...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-0231
更新日期：2007-10-01 00:00:00
abstract：Purpose:Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation. Toll-like receptors (TLRs) are integral in the initiation of inflammatory signaling. Therefore, we evaluated the effect of TLR-deficiency on dry eye-related ocular surface damage and inflammation using a mouse model o...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.17-23397
更新日期：2018-06-01 00:00:00
abstract：PURPOSE:To compare spectral-domain optical coherence tomography (SD-OCT) standard structural measures and a new three-dimensional (3D) volume optic nerve head (ONH) change detection method for detecting change over time in severely advanced-glaucoma (open-angle glaucoma [OAG]) patients. METHODS:Thirty-five eyes of 35 ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章,多中心研究
doi：10.1167/iovs.15-18929
更新日期：2016-07-01 00:00:00
