Treatment of Inherited Eye Defects by Systemic Hematopoietic Stem Cell Transplantation.

Abstract:

PURPOSE:Cystinosis is caused by a deficiency in the lysosomal cystine transporter, cystinosin (CTNS gene), resulting in cystine crystal accumulation in tissues. In eyes, crystals accumulate in the cornea causing photophobia and eventually blindness. Hematopoietic stem progenitor cells (HSPCs) rescue the kidney in a mouse model of cystinosis. We investigated the potential for HSPC transplantation to treat corneal defects in cystinosis. METHODS:We isolated HSPCs from transgenic DsRed mice and systemically transplanted irradiated Ctns-/- mice. A year posttransplantation, we investigated the fate and function of HSPCs by in vivo confocal and fluorescence microscopy (IVCM), quantitative RT-PCR (RT-qPCR), mass spectrometry, histology, and by measuring the IOP. To determine the mechanism by which HSPCs may rescue disease cells, we transplanted Ctns-/- mice with Ctns-/- DsRed HSPCs virally transduced to express functional CTNS-eGFP fusion protein. RESULTS:We found that a single systemic transplantation of wild-type HSPCs prevented ocular pathology in the Ctns-/- mice. Engraftment-derived HSPCs were detected within the cornea, and also in the sclera, ciliary body, retina, choroid, and lens. Transplantation of HSPC led to substantial decreases in corneal cystine crystals, restoration of normal corneal thickness, and lowered IOP in mice with high levels of donor-derived cell engraftment. Finally, we found that HSPC-derived progeny differentiated into macrophages, which displayed tunneling nanotubes capable of transferring cystinosin-bearing lysosomes to diseased cells. CONCLUSIONS:To our knowledge, this is the first demonstration that HSPCs can rescue hereditary corneal defects, and supports a new potential therapeutic strategy for treating ocular pathologies.

authors

Rocca CJ,Kreymerman A,Ur SN,Frizzi KE,Naphade S,Lau A,Tran T,Calcutt NA,Goldberg JL,Cherqui S

doi

10.1167/iovs.15-17107

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

7214-23

issue

12

eissn

0146-0404

issn

1552-5783

pii

2469222

journal_volume

56

pub_type

杂志文章
  • Orientation Tuning and Contrast Dependence of Continuous Flash Suppression in Amblyopia and Normal Vision.

    abstract:Purpose:Suppression in amblyopia may be an unequal form of normal interocular suppression or a distinct pathophysiology. To explore this issue, we examined the orientation tuning and contrast dependence of continuous flash suppression (CFS) in adults with amblyopia and visually normal controls. Methods:Nine patients (...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.18-23954

    authors: Gao TY,Ledgeway T,Lie AL,Anstice N,Black J,McGraw PV,Thompson B

    更新日期:2018-11-01 00:00:00

  • Retinal and Choroidal Microvasculature in Nonarteritic Anterior Ischemic Optic Neuropathy: An Optical Coherence Tomography Angiography Study.

    abstract:Purpose:To analyze retinal and choroidal microvasculature in patients with nonarteritic anterior ischemic optic neuropathy (NAION) by using optical coherence tomography angiography (OCT-A). Methods:In this case-control retrospective observational study, patients with atrophic NAION (at least 3 months after onset of sy...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.17-22996

    authors: Augstburger E,Zéboulon P,Keilani C,Baudouin C,Labbé A

    更新日期:2018-02-01 00:00:00

  • Difluprednate 0.05% versus prednisolone acetate 1% for endogenous anterior uveitis: a phase III, multicenter, randomized study.

    abstract:PURPOSE:Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition. METHODS:This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogeno...

    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.13-12660

    authors: Sheppard JD,Toyos MM,Kempen JH,Kaur P,Foster CS

    更新日期:2014-05-06 00:00:00

  • Modulation of inflammatory markers by miR-146a during replicative senescence in trabecular meshwork cells.

    abstract:PURPOSE:To investigate the alterations in microRNA (miRNA) expression during replicative senescence (RS) in human trabecular meshwork (HTM) cells. METHODS:Two HTM cell lines were serially passaged until they reached RS. Changes in expression of 30 miRNAs were assessed by real-time quantitative (q)-PCR. The effects of ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.09-4874

    authors: Li G,Luna C,Qiu J,Epstein DL,Gonzalez P

    更新日期:2010-06-01 00:00:00

  • Eye movements in schizophrenia.

    abstract::Smooth pursuit and other eye movements were quantitatively studied in patients with chronic schizophrenia to characterize the pattern and severity of eye movement abnormalities in this disorder. Twenty-one patients with schizophrenia, 13 patients with other psychiatric disorders (manic-depressive psychosis, schizoaffe...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Yee RD,Baloh RW,Marder SR,Levy DL,Sakala SM,Honrubia V

    更新日期:1987-02-01 00:00:00

  • The minimum precorneal oxygen tension to avoid corneal edema.

    abstract::One eye of each of eight subjects was exposed to gases containing oxygen concentrations of 1.0%, 2.5%, 4.9%, 7.5%, 10.1%, and 21.4% (oxygen partial pressures ranging from 8 to 158 mmHg) for 8 hr. The precorneal oxygen concentration required to avoid corneal edema for the group as a whole was 10.1% (an oxygen tension o...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Holden BA,Sweeney DF,Sanderson G

    更新日期:1984-04-01 00:00:00

  • The Effect of Light Level and Small Pupils on Presbyopic Reading Performance.

    abstract:Purpose:To examine the impact of small pupils and light levels on reading performance of distance-corrected presbyopes. To determine whether small pupils would enable presbyopes to read at near even at low light levels. Methods:To establish the lower range of text luminances, we quantified the space-averaged luminance...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.16-20008

    authors: Xu R,Gil D,Dibas M,Hare W,Bradley A

    更新日期:2016-10-01 00:00:00

  • Role of metallothioneins 1 and 2 in ocular neovascularization.

    abstract:PURPOSE:The incidence of blindness is increasing, in part, because of abnormal ocular neovascularization. Anti-VEGF therapies have yielded impressive results; however, they are not a cure for blindness. Recently, metallothioneins (MTs) 1 and 2 have been implicated in the process of angiogenesis. Therefore, we investiga...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.14-14545

    authors: Nakamura S,Shimazawa M,Inoue Y,Takata S,Ito Y,Tsuruma K,Ikeda T,Honda A,Satoh M,Hara H

    更新日期:2014-09-23 00:00:00

  • The oscillatory potentials of the mudpuppy retina.

    abstract::The properties of the oscillatory potentials (OPs) of the mudpuppy electroretinogram (ERG) were studied and compared with the properties of the b-wave of the ERG and the proximal negative response (PNR). Both transretinal and intraretinal ERGs were recorded in response to full-field as well as 200 and 500 microgram sp...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Wachtmeister L,Dowling JE

    更新日期:1978-12-01 00:00:00

  • Human Parafoveal Capillary Vascular Anatomy and Connectivity Revealed by Optical Coherence Tomography Angiography.

    abstract:Purpose:To assess the connection among arterioles, venules, and capillaries in three retinal capillary plexuses using optical coherence tomography angiography (OCTA). Methods:This was a prospective, cross-sectional, observational study including 20 eyes of 10 healthy subjects. En face and cross-sectional OCTA images w...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.18-24710

    authors: Nesper PL,Fawzi AA

    更新日期:2018-08-01 00:00:00

  • In vitro and in vivo susceptibility of Candida keratitis to topical polyenes.

    abstract::The susceptibility of Candida albicans to topical amphotericin B and natamycin was evaluated in a model of stromal keratitis in Dutch-belted rabbits and compared with minimal inhibitory concentrations in vitro. Treatment was delayed 24 hr to allow invasive disease to occur and was then continued for 5 days. Ten strain...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: O'Day DM,Ray WA,Robinson RD,Head WS,Savage AM

    更新日期:1987-05-01 00:00:00

  • Endothelium-dependent regulation of the ophthalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelins.

    abstract:PURPOSE:The endothelium produces nitric oxide and endothelin (ET). This study was designed to investigate the endothelium-dependent regulation of the porcine ophthalmic microcirculation. METHODS:Isolated porcine eyes were perfused with a modified Langendorff setup (Hugo Sachs Elektronik KG, Freiburg, Germany) at a per...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Meyer P,Flammer J,Lüscher TF

    更新日期:1993-12-01 00:00:00

  • Microvascular Density Is Associated With Retinal Ganglion Cell Axonal Volume in the Laminar Compartments of the Human Optic Nerve Head.

    abstract:Purpose:To quantify associations between microvascular density and retinal ganglion cell (RGC) axonal volume in the laminar compartments of the human optic nerve head (ONH). Methods:Eleven normal human ONHs were evaluated. Antibodies were used to label the vascular endothelium (factor VIII-related antigen/von Willebra...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.17-23183

    authors: Kang MH,Suo M,Balaratnasingam C,Yu PK,Morgan WH,Yu DY

    更新日期:2018-03-01 00:00:00

  • Inhibition of hemangiogenesis and lymphangiogenesis after normal-risk corneal transplantation by neutralizing VEGF promotes graft survival.

    abstract:PURPOSE:To evaluate the occurrence and time course of hem- and lymphangiogenesis after normal-risk corneal transplantation in the mouse model and to test whether pharmacologic strategies inhibiting both processes improve long-term graft survival. METHODS:Normal-risk allogeneic (C57BL/6 to BALB/c) and syngeneic (BALB/c...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.03-1380

    authors: Cursiefen C,Cao J,Chen L,Liu Y,Maruyama K,Jackson D,Kruse FE,Wiegand SJ,Dana MR,Streilein JW

    更新日期:2004-08-01 00:00:00

  • Replication of the recessive STBMS1 locus but with dominant inheritance.

    abstract:PURPOSE:Strabismus is a common eye disorder with a prevalence of 1% to 4%. Comitant strabismus accounts for approximately 75% of all strabismus, yet more is known about the less common incomitant disorders. Comitant strabismus is at least partly inherited, but only one recessive genetic susceptibility locus, on chromos...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.07-1631

    authors: Rice A,Nsengimana J,Simmons IG,Toomes C,Hoole J,Willoughby CE,Cassidy F,Williams GA,George ND,Sheridan E,Young TL,Hunter TI,Barrett BT,Elliott DB,Bishop DT,Inglehearn CF

    更新日期:2009-07-01 00:00:00

  • Overt Proteinuria, Moderately Reduced eGFR and Their Combination Are Predictive of Severe Diabetic Retinopathy or Diabetic Macular Edema in Diabetes.

    abstract:Purpose:Since the combined effects of proteinuria and a moderately decreased eGFR on incident severe eye complications in patients with diabetes are still largely unknown, these associations were determined in a large historical cohort of Japanese patients with diabetes mellitus. Methods:We evaluated the effects of ov...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.19-26749

    authors: Yamamoto M,Fujihara K,Ishizawa M,Osawa T,Kaneko M,Ishiguro H,Matsubayashi Y,Seida H,Yamanaka N,Tanaka S,Kodama S,Hasebe H,Sone H

    更新日期:2019-06-03 00:00:00

  • Directed Differentiation of Human Corneal Endothelial Cells From Human Embryonic Stem Cells by Using Cell-Conditioned Culture Media.

    abstract:Purpose:A shortage of human corneal endothelial cells (HCEC) for transplant and current methods of differentiation induction require chemical compounds, which might cast further influences after differentiation induction. Therefore, we developed a simple and straightforward approach to endothelial cell differentiation ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.17-23627

    authors: Chen X,Wu L,Li Z,Dong Y,Pei X,Huang Y,Wang L

    更新日期:2018-06-01 00:00:00

  • Vitreous macrophage elicitation: generation of stimulants for pigment epithelium in vitro.

    abstract::Vitreous and macrophage samples were tested for the ability to stimulate proliferation and cell migration in cultured rabbit retinal pigment epithelium (RPE). A macrophage invasion was elicited by the intravitreal injection of latex particles in rabbits and after 3 days the vitreal macrophages were collected. The macr...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Burke JM,Twining SS

    更新日期:1987-07-01 00:00:00

  • Nuclear gene expression changes due to mitochondrial dysfunction in ARPE-19 cells: implications for age-related macular degeneration.

    abstract:PURPOSE:To measure changes in nuclear gene expression resulting from mitochondrial dysfunction in retinal pigment epithelial cells. METHODS:ARPE-19 retinal pigment epithelial cells were depleted of their mitochondrial (mt)DNA by passaging in a low concentration of ethidium bromide. Loss of mitochondrial DNA was determ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.04-1327

    authors: Miceli MV,Jazwinski SM

    更新日期:2005-05-01 00:00:00

  • A new tonometer--the Corvis ST tonometer: clinical comparison with noncontact and Goldmann applanation tonometers.

    abstract:PURPOSE:To compare intraocular pressure (IOP) measurements obtained using the Topocon noncontact tonometer (NCT), the Goldmann applanation tonometer (GAT), and the Corvis ST (CST), a newly developed tonometer with features of visualization and measurement of the corneal deformation response to an air impulse. A seconda...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.12-10984

    authors: Hong J,Xu J,Wei A,Deng SX,Cui X,Yu X,Sun X

    更新日期:2013-01-23 00:00:00

  • Anti-Inflammatory Effect of Dexamethasone Controlled Released From Anterior Suprachoroidal Polyurethane Implants on Endotoxin-Induced Uveitis in Rats.

    abstract:PURPOSE:Targeted drug delivery to the ocular tissues remains a challenge. Biodegradable intraocular implants allow prolonged controlled release of drugs directly into the eye. In this study, we evaluated an anterior suprachoroidal polyurethane implant containing dexamethasone polyurethane dispersions (DX-PUD) as a drug...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.15-18127

    authors: Barbosa Saliba J,Vieira L,Fernandes-Cunha GM,Rodrigues Da Silva G,Ligório Fialho S,Silva-Cunha A,Bousquet E,Naud MC,Ayres E,Oréfice RL,Tekaya M,Kowalczuk L,Zhao M,Behar-Cohen F

    更新日期:2016-04-01 00:00:00

  • Intravitreal injection of AAV2 transduces macaque inner retina.

    abstract:PURPOSE:Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized mo...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.10-6250

    authors: Yin L,Greenberg K,Hunter JJ,Dalkara D,Kolstad KD,Masella BD,Wolfe R,Visel M,Stone D,Libby RT,Diloreto D Jr,Schaffer D,Flannery J,Williams DR,Merigan WH

    更新日期:2011-04-25 00:00:00

  • Abundant expression of ponsin, a focal adhesion protein, in lens and downregulation of its expression by impaired cytoskeletal signaling.

    abstract:PURPOSE:This study was undertaken to improve understanding of the defective lens developmental changes induced by the transgenic overexpression of the Rho GDP dissociation inhibitor RhoGDIalpha. The study was focused on a single differentially expressed gene encoding ponsin, a cell adhesion interacting signaling adapto...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.08-2909

    authors: Rao PV,Maddala R

    更新日期:2009-04-01 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

    doi:

    authors: Serafano DM,Brubaker RF

    更新日期:1978-01-01 00:00:00

  • Individual variation in size of the human red and green visual pigment gene array.

    abstract:PURPOSE:To determine the size variation of the X-chromosomal human red and green visual pigment gene array in the general population using pulsed field gel electrophoresis and Southern blotting. METHODS:Peripheral blood lymphocytes were prepared from 67 anonymous males. The cells were embedded in agarose and the genom...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:

    authors: Macke JP,Nathans J

    更新日期:1997-04-01 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

    doi:

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

    更新日期:1993-11-01 00:00:00

  • Retinal Glial and Choroidal Vascular Pathology in Donors Clinically Diagnosed With Stargardt Disease.

    abstract:Purpose:The present study investigated retinal glia and choroidal vessels in flatmounts and sections from individuals with clinically diagnosed Stargardt disease (STGD). Methods:Eyes from three donors clinically diagnosed with STGD were obtained through the Foundation Fighting Blindness (FFB). Genetic testing was perf...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.61.8.27

    authors: Edwards MM,Bonilha VL,Bhutto IA,Bell BA,McLeod DS,Hollyfield JG,Lutty GA

    更新日期:2020-07-01 00:00:00

  • A Novel Luciferase Assay For Sensitively Monitoring Myocilin Variants in Cell Culture.

    abstract:PURPOSE:Primary open angle glaucoma-associated mutations in myocilin (MYOC) cause protein "nonsecretion," rendering secreted MYOC difficult to detect using conventional techniques. This study focused on developing and using an assay that can quickly and easily detect mutant MYOC secretion. METHODS:We fused Gaussia luc...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.15-18789

    authors: Zadoo S,Nguyen A,Zode G,Hulleman JD

    更新日期:2016-04-01 00:00:00

  • Downregulation of Lysyl Oxidase Protects Retinal Endothelial Cells From High Glucose-Induced Apoptosis.

    abstract:Purpose:To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Methods:Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG me...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.16-21340

    authors: Kim D,Mecham RP,Trackman PC,Roy S

    更新日期:2017-05-01 00:00:00

  • Visually impaired drivers who use bioptic telescopes: self-assessed driving skills and agreement with on-road driving evaluation.

    abstract:PURPOSE:To compare self-assessed driving habits and skills of licensed drivers with central visual loss who use bioptic telescopes to those of age-matched normally sighted drivers, and to examine the association between bioptic drivers' impressions of the quality of their driving and ratings by a "backseat" evaluator. ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章

    doi:10.1167/iovs.13-13520

    authors: Owsley C,McGwin G Jr,Elgin J,Wood JM

    更新日期:2014-01-15 00:00:00