Subcellular distribution and activity of mechanistic target of rapamycin in aged retinal pigment epithelium.


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.


Yu B,Xu P,Zhao Z,Cai J,Sternberg P,Chen Y




Has Abstract


2014-12-09 00:00:00














  • Laser scanning in vivo confocal microscopy of the normal human corneoscleral limbus.

    abstract:PURPOSE:To elucidate the structure of the human corneoscleral limbus by in vivo laser scanning confocal microscopy and to correlate limbal epithelial dimensions and density with the central epithelium and in relation to age. METHODS:Fifty adult subjects were recruited into one of two age groups: younger (age<45 years)...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Patel DV,Sherwin T,McGhee CN

    更新日期:2006-07-01 00:00:00

  • Interrelationship of optical coherence tomography and multifocal visual-evoked potentials after optic neuritis.

    abstract:PURPOSE:Acute optic neuritis (ON) is often followed by recovery of visual function. Although this recovery is mainly attributable to resolution of the acute inflammation, the redistribution of ion channels along the demyelinated membrane, and subsequent remyelination, part of it may be the result of neural plasticity. ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Klistorner A,Arvind H,Garrick R,Graham SL,Paine M,Yiannikas C

    更新日期:2010-05-01 00:00:00

  • Protective effect of pioglitazone on retinal ischemia/reperfusion injury in rats.

    abstract:PURPOSE:To investigate the protective effect of pioglitazone on the rat retina after ischemia/reperfusion (I/R) injury and to explore its possible mechanisms. METHODS:Retinal ischemia was induced by increasing the intraocular pressure to 110 mm Hg for 60 minutes, and pioglitazone was delivered 3 hours before the I/R. ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Zhang XY,Xiao YQ,Zhang Y,Ye W

    更新日期:2013-06-06 00:00:00

  • Comparison of time-domain OCT and fundus photographic assessments of retinal thickening in eyes with diabetic macular edema.

    abstract:PURPOSE:To explore the correlation between optical coherence tomography (OCT) and stereoscopic fundus photographs (FP) for the assessment of retinal thickening (RT) in diabetic macular edema (DME) within a clinical trial. METHODS:OCT, FP, and best corrected visual acuity (VA) measurements were obtained in both eyes of...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Davis MD,Bressler SB,Aiello LP,Bressler NM,Browning DJ,Flaxel CJ,Fong DS,Foster WJ,Glassman AR,Hartnett ME,Kollman C,Li HK,Qin H,Scott IU,Diabetic Retinopathy Clinical Research Network Study Group.

    更新日期:2008-05-01 00:00:00

  • Linkage of a mild late-onset phenotype of Fuchs corneal dystrophy to a novel locus at 5q33.1-q35.2.

    abstract:PURPOSE:To identify the disease locus associated with autosomal dominant Fuchs corneal dystrophy (FCD) in a large family and to compare the progression of severity in families mapped to the FCD1 and FCD2 loci. METHODS:Seventeen individuals in a large family were examined by slit lamp biomicroscopy. Blood samples were ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Riazuddin SA,Eghrari AO,Al-Saif A,Davey L,Meadows DN,Katsanis N,Gottsch JD

    更新日期:2009-12-01 00:00:00

  • Iris arteriolar diameters in hypoxia and hyperoxia: a photographic study in albino guinea pigs.

    abstract::The irides of albino guinea pigs were photographed, and the iris arteriolar diameters were measured with the animal breathing room air, 10% O2/90% N2, or 100% O2. The iris arterioles constrict significantly in hyperoxia and dilate in hypoxia. The average constriction in 100% O2 was 27% +/- 8%, and the average dilatati...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Stefansson E,Shelton RA,Landers MB 3rd,Walsh AW,Wolbarsht ML

    更新日期:1983-06-01 00:00:00

  • Contributing factors to corneal deformation in air puff measurements.

    abstract:PURPOSE:Air puff systems have been presented recently to measure corneal biomechanical properties in vivo. In our study we tested the influence of several factors on corneal deformation to an air puff: IOP, corneal rigidity, dehydration, presence of sclera, and in vivo versus in vitro conditions. METHODS:We used 14 fr...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Kling S,Marcos S

    更新日期:2013-07-26 00:00:00

  • Survival of Alpha and Intrinsically Photosensitive Retinal Ganglion Cells in NMDA-Induced Neurotoxicity and a Mouse Model of Normal Tension Glaucoma.

    abstract:Purpose:We assess if α retinal ganglion cells (αRGCs) and intrinsically photosensitive retinal ganglion cells (ipRGCs) survive in mouse models of glaucoma. Methods:Two microliters of N-methyl-D-aspartate (NMDA; 1 mM) or PBS were injected intraocularly 7 days before sacrifice. Immunohistochemical analyses of the retina...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Honda S,Namekata K,Kimura A,Guo X,Harada C,Murakami A,Matsuda A,Harada T

    更新日期:2019-09-03 00:00:00

  • Androgen influence on the meibomian gland.

    abstract:PURPOSE:The hypothesis in the study was that androgens control meibomian gland function, regulate the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer. To test this hypothesis, a study was conducted to determine whether androgen receptor protein exists ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Sullivan DA,Sullivan BD,Ullman MD,Rocha EM,Krenzer KL,Cermak JM,Toda I,Doane MG,Evans JE,Wickham LA

    更新日期:2000-11-01 00:00:00

  • Regulation of paracrine cytokine balance controlling collagenase synthesis by corneal cells.

    abstract:PURPOSE:Classic studies have demonstrated that corneal epithelial cell density in culture can alter the balance of stimulatory and inhibitory cytokines controlling the elaboration of collagenolytic activity by co-cultured stromal cells. The current study attempts to bring the understanding of this mechanism to a molecu...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Strissel KJ,Rinehart WB,Fini ME

    更新日期:1997-02-01 00:00:00

  • Ocular penetration of N-formimidoyl thienamycin (MK-787) and potentiation by dipeptidase inhibitor (MK-791).

    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


    authors: Finlay KR,Carlson CL,Chow AW

    更新日期:1983-08-01 00:00:00

  • Difference in the properties of retinal nerve fiber layer defect between superior and inferior visual field loss in glaucoma.

    abstract:PURPOSE:To investigate the patterns of retinal nerve fiber layer (RNFL) defects in mean deviation-matched early glaucomatous eyes with either superior or inferior visual hemifield loss. METHODS:Seventy-five open-angle glaucoma patients with isolated parafoveal scotoma (PFS) within a central 10° of fixation, and 62 pat...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Choi JA,Park HY,Jung KI,Hong KH,Park CK

    更新日期:2013-10-23 00:00:00

  • Clinical Characteristics, Mutation Spectrum, and Prevalence of Åland Eye Disease/Incomplete Congenital Stationary Night Blindness in Denmark.

    abstract:Purpose:To assess clinical characteristics, foveal structure, mutation spectrum, and prevalence rate of Åland eye disease (AED)/incomplete congenital stationary night blindness (iCSNB). Methods:A retrospective survey included individuals diagnosed with AED at a national low-vision center from 1980 to 2014. A subset of...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Hove MN,Kilic-Biyik KZ,Trotter A,Grønskov K,Sander B,Larsen M,Carroll J,Bech-Hansen T,Rosenberg T

    更新日期:2016-12-01 00:00:00

  • A novel in vitro model to study staphylococcal biofilm formation on intraocular lenses under hydrodynamic conditions.

    abstract:PURPOSE:To develop a novel in vitro model to study the formation of Staphylococcus epidermidis biofilm on intraocular lenses (IOLs) from the primary-attachment phase to the biofilm-accumulation phase. The model was designed to replicate intraocular conditions especially by taking into account intraocular hydrodynamics....

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Baillif S,Casoli E,Marion K,Roques C,Pellon G,Hartmann DJ,Freney J,Burillon C,Kodjikian L

    更新日期:2006-08-01 00:00:00

  • Targeted transgene expression in muller glia of normal and diseased retinas using lentiviral vectors.

    abstract:PURPOSE:Müller glia play crucial roles in retinal homeostasis and function. Genetic modification of Müller cells by viral gene delivery would be valuable for studies of their normal physiology and roles in retinal disease states. However, stable and efficient transgene expression in Müller cells after delivery of gene ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Greenberg KP,Geller SF,Schaffer DV,Flannery JG

    更新日期:2007-04-01 00:00:00

  • Baseline OCT measurements in the idiopathic intracranial hypertension treatment trial, part I: quality control, comparisons, and variability.

    abstract:PURPOSE:Optical coherence tomography (OCT) has been used to investigate papilledema in single-site, mostly retrospective studies. We investigated whether spectral-domain OCT (SD-OCT), which provides thickness and volume measurements of the optic nerve head and retina, could reliably demonstrate structural changes due t...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 临床试验,杂志文章,多中心研究


    authors: OCT Sub-Study Committee for NORDIC Idiopathic Intracranial Hypertension Study Group.,Auinger P,Durbin M,Feldon S,Garvin M,Kardon R,Keltner J,Kupersmith M,Sibony P,Plumb K,Wang JK,Werner JS

    更新日期:2014-11-04 00:00:00

  • Intraocular pressure after optic nerve transection.

    abstract::Intraocular pressure response to systemically administered osmotic agents was studied in albino rabbits with one optic nerve transected and the fellow optic nerve left intact. There eas a significant increase in intraocular pressure of both eyes following water ingestion but no significant difference in the pressure r...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Serafano DM,Brubaker RF

    更新日期:1978-01-01 00:00:00

  • Global Visit Effects in Point-Wise Longitudinal Modeling of Glaucomatous Visual Fields.

    abstract:PURPOSE:One of the difficulties in modeling visual field (VF) data is the sometimes large and correlated measurement errors in the point-wise sensitivity estimates. As these errors affect all locations of the same VF, we propose to model them as global visit effects (GVE). We evaluate this model and show the effect it ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Bryan SR,Eilers PH,Lesaffre EM,Lemij HG,Vermeer KA

    更新日期:2015-07-01 00:00:00

  • Analysis of immunosuppressive properties of iris and ciliary body cells and their secretory products.

    abstract::The anterior chamber of the eye is an immunosuppressive microenvironment as shown experimentally by immune privilege, anterior chamber-associated immune deviation, and inability to display local delayed-type hypersensitivity responses. It recently was reported that both the aqueous humor and the cells of the iris and ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Streilein JW,Bradley D

    更新日期:1991-09-01 00:00:00

  • Cholinergic agonists activate P2X7 receptors to stimulate protein secretion by the rat lacrimal gland.

    abstract:PURPOSE:To determine the interaction of M3 muscarinic receptors (M3AChR) and P2X(7) receptors to increase intracellular [Ca2+] ([Ca2+]i) and stimulate protein secretion in rat lacrimal gland cells. METHODS:Exorbital lacrimal glands from male Sprague-Dawley rats were divided into pieces or digested with collagenase to ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Dartt DA,Hodges RR

    更新日期:2011-05-01 00:00:00

  • Prophylactic acyclovir effectively reduces herpes simplex virus type 1 reactivation after exposure of latently infected mice to ultraviolet B.

    abstract:PURPOSE:To determine the potential efficacy and anatomic sites of action of prophylactic oral acyclovir using a murine model of ultraviolet-B-induced reactivation of herpes simplex 1 keratitis. METHODS:Latent infection with herpes simplex 1 (McKrae) was established in 80 National Institutes of Health inbred strain of ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Blatt AN,Laycock KA,Brady RH,Traynor P,Krogstad DJ,Pepose JS

    更新日期:1993-11-01 00:00:00

  • Electrophysiological and psychophysical differences between early- and late-onset strabismic amblyopia.

    abstract:PURPOSE:To compare visual evoked potentials (VEPs) and contrast sensitivity in adults with early- or late-onset strabismic amblyopia. METHODS:Twelve adults with early- and 12 with late-onset strabismic amblyopia with similar ranges of visual acuity were studied. Pattern-onset VEPs to 30-minute checks were recorded at ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Davis AR,Sloper JJ,Neveu MM,Hogg CR,Morgan MJ,Holder GE

    更新日期:2003-02-01 00:00:00

  • Microarray characterization of human embryonic stem cell--derived retinal cultures.

    abstract:PURPOSE:A number of protocols have been published to induce retinal determination from human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC). Although all these studies have shown some degree of expression of markers of retinal cells, fewer than 30 markers are typically used to characterize the ES...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Lamba DA,Reh TA

    更新日期:2011-07-01 00:00:00

  • In Vivo Assessment of Pharmacologic Vitreolysis in Rabbits With the Digital Fluoroscopy System.

    abstract:PURPOSE:The purpose of this study was to demonstrate the efficacy of the digital fluoroscopy system (DFS) for the in vivo assessment of pharmacologically induced posterior vitreous detachment (PVD) and vitreous liquefaction in a rabbit model. METHODS:Twenty eyes from 10 New Zealand white rabbits were divided into 5 gr...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Bae JH,Park HS,Kim JM,Lee BR,Lee SC,Tandogan T,Auffarth GU,Koss MJ,Choi CY

    更新日期:2015-07-01 00:00:00

  • Methionine sulfoxide reductases B1, B2, and B3 are present in the human lens and confer oxidative stress resistance to lens cells.

    abstract:PURPOSE:Methionine-sulfoxide reductases are unique, in that their ability to repair oxidized proteins and MsrA, which reduces S-methionine sulfoxide, can protect lens cells against oxidative stress damage. To date, the roles of MsrB1, -B2 and -B3 which reduce R-methionine sulfoxide have not been established for any mam...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Marchetti MA,Pizarro GO,Sagher D,Deamicis C,Brot N,Hejtmancik JF,Weissbach H,Kantorow M

    更新日期:2005-06-01 00:00:00

  • Characteristics of a glycoprotein in the ocular surface glycocalyx.

    abstract::A monoclonal antibody has been produced that binds to the apical squames (flattened cells) of the rat ocular surface epithelium and to the goblet cells of the conjunctiva. Immunoelectron microscopic localization of the antigen indicates that in apical cells it is present along the apical-microplical membrane in the re...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Gipson IK,Yankauckas M,Spurr-Michaud SJ,Tisdale AS,Rinehart W

    更新日期:1992-01-01 00:00:00

  • Anti-retinal antibodies in serum of laser-treated rabbits.

    abstract:PURPOSE:Retinal injuries that affect the photoreceptors and/or the retinal pigment epithelium (RPE) may result in the leakage of retinal proteins into the systemic circulation. This study was designed to determine whether an immune response is elicited after an acute retinal injury resulting in circulating anti-retinal...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Scott SE,Bouhenni RA,Chomyk AM,Dunmire JJ,Patil J,Nakamura H,Deepak P

    更新日期:2012-04-06 00:00:00

  • Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics.

    abstract:Purpose:Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and approximately half of those diagnosed will die of metastasis. This study investigates whether UM progression is driven by a subpopulation of stem-like cells, termed "cancer stem cells" (CSCs). Methods:Expression of postulated s...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Doherty RE,Sisley K,Hammond DW,Rennie IG,Cross NA

    更新日期:2017-10-01 00:00:00

  • Early TIMP gene expression after corneal infection with Pseudomonas aeruginosa.

    abstract:PURPOSE:To evaluate the expression of tissue inhibitor of metalloproteinases (TIMP) mRNA in corneal tissues before and at early time points (6 and 12 hours and 1, 3, and 5 days) after corneal infection with Pseudomonas aeruginosa. METHODS:Ribonuclease protection assays were used to detect and quantitate TIMP mRNA expr...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Kernacki KA,Goebel DJ,Poosch MS,Hazlett LD

    更新日期:1998-02-01 00:00:00

  • Improvement of Photoreceptor Targeting via Intravitreal Delivery in Mouse and Human Retina Using Combinatory rAAV2 Capsid Mutant Vectors.

    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


    authors: Reid CA,Ertel KJ,Lipinski DM

    更新日期:2017-12-01 00:00:00