Abstract:
PURPOSE:Erythropoietin (EPO) modulates erythropoiesis by inhibiting apoptosis in erythrocyte progenitors. Recently, EPO has been shown to be protective in experimental models of mechanical trauma, neuroinflammation, cerebral and retinal ischemia, and even in a human stroke trial. However, little is known about EPO signal transduction in vivo and the usefulness of EPO in the prevention of the chronic, purely apoptotic neuronal cell death that contributes to vision loss in glaucoma and the progression of neurodegenerative diseases. METHODS:EPO's effects and signaling in the retinal ganglion cell axotomy paradigm were studied by Western blot analysis and immunohistochemistry, receptor expression was characterized in the retina before and after lesion. EPO was injected into the vitreous body to investigate neuroprotection of axotomized rat RGCs. Moreover, EPO's effects were studied in cultures of immunopurified retinal ganglion cells. Signal-transduction pathways transmitting neuroprotective EPO effects in vivo were characterized by the use of specific kinase inhibitors, immunohistochemistry, and Western blot analysis. RESULTS:EPO receptors (EPORs) were expressed on RGC somata and dendrites in vivo. EPOR expression did not significantly change after axotomy. Application of EPO prevented death of neurotrophic-factor-deprived immunopurified rat RGCs in vitro, rescued axotomized RGCs in vivo, and prevented caspase-3 activation. EPO-induced Akt phosphorylation and survival-promoting EPO effects were completely abolished by inhibition of PI-3-kinase. EPO neuroprotection followed a bell-shaped dose-response curve in vitro and in vivo, whereas toxic EPO effects were never observed, even at high concentrations. CONCLUSIONS:These data support a potential role for EPO as a therapeutic molecule against predominantly apoptotic neuronal cell death in the context of glaucoma or neurodegenerative diseases and delineate the PI-3-K/Akt pathway as the predominant mediator of EPO neuroprotection in this in vivo paradigm of neuronal cell death.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Weishaupt JH,Rohde G,Pölking E,Siren AL,Ehrenreich H,Bähr Mdoi
10.1167/iovs.03-1039keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
1514-22issue
5eissn
0146-0404issn
1552-5783journal_volume
45pub_type
杂志文章abstract:PURPOSE:The objective of this study was to determine whether alteration in mucins could be detected in patients with dry eye symptoms by using the monoclonal antibody H185, which recognizes carbohydrate epitopes on mucin molecules. METHODS:Immunohistochemistry and immunoelectron microscopy was used to examine binding ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::Monoclonal antibody to HSV glycoprotein D was derivatized with palmitic acid and incorporated into liposomes. These immunoliposomes bound specifically to intact mouse corneas infected with HSV-1 in vitro. Furthermore, in yield reduction assays, anti-gD immunoliposomes loaded with acyclovir proved far more effective at...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract:PURPOSE:To examine the in vitro properties of gap junctions on the isolated rabbit ciliary epithelium. METHODS:Intracellular potential was measured and lucifer yellow (5% in 1 M LiCl) was iontophoretically injected into a ciliary epithelial cell. Fixated tissue was examined with a laser confocal microscope. RESULTS:D...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract:PURPOSE:To evaluate the short- and long-term changes of focal macular electroretinograms (fmERGs) after macular translocation with 360 degrees retinotomy. METHODS:This was a retrospective study. fmERGs were recorded in 19 eyes of 19 consecutive patients who underwent macular translocation with 360 degrees retinotomy f...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0187
更新日期:2004-02-01 00:00:00
abstract:PURPOSE:Cortical cataract in humans is associated with Ca2+ overload and protein loss, and although animal models of cataract have implicated Ca2+-activated proteases in this process, it remains to be determined whether the human lens responds in this manner to conditions of Ca2+ overload. The purpose of these experime...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract:PURPOSE:Macular pigment optical density (MPOD) and age-related macular degeneration (AMD) are thought to be associated; however, the details are not yet understood clearly. This study aimed at investigating how retinal anatomic structures relate with the spatial MPOD distribution in single eyes. METHODS:In a subgroup ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12903
更新日期:2014-02-26 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-11969
更新日期:2013-08-27 00:00:00
abstract:PURPOSE:Ca(2+) is a major regulator of cell function. In the retinal pigment epithelium (RPE), intracellular free Ca(2+) concentration ([Ca(2+)](i)) is essential for the maintenance of normal retinal function. Therefore, accurate control of [Ca(2+)](i) is vital in these cells. Because Ca(2+) is permanently extruded fro...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0412
更新日期:2007-12-01 00:00:00
abstract:Purpose:Conjunctival squamous cell carcinoma (SCC), a type of ocular surface neoplasia, is primarily treated by surgical resection and topical immuno- or chemotherapy. Metastatic disease may be treated with systemic chemo- or immunotherapy, albeit with variable response. The purpose of this study was to determine wheth...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2019-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00
abstract:Purpose:To test the hypothesis that emmetropization buffers against genetic and environmental risk factors for myopia by investigating whether risk factor effect sizes vary depending on children's position in the refractive error distribution. Methods:Refractive error was assessed in participants from two birth cohort...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2020-02-07 00:00:00
abstract:PURPOSE:The structure of collagen lamellae in the anterior stroma of the human cornea is thought to be an important determinant of corneal rigidity. The three-dimensional structure of such collagen lamellae in normal human corneas was examined. METHODS:The anterior portion of 27 normal human corneas was obtained from ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5657
更新日期:2011-02-16 00:00:00
abstract:Purpose:During development, the corneal epithelium (CE) and the conjunctiva are derived from the surface ectoderm. Here we have examined how, during development, the cells of these two issues become isolated from each other. Methods:Epithelia from the anterior eyes of chicken embryos were labeled with the fluorescent,...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-20737
更新日期:2017-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0178
更新日期:2004-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4348
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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::Chronic blepharitis has been a difficult disease to define either microbiologically or biochemically. Sterols from meibomian secretions of normal subjects and patients were analyzed, and important differences were observed. Based on analyses of these secretions, two significantly different (P less than 0.001) types of...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1991-07-01 00:00:00
abstract:PURPOSE:To identify the underlying molecular defects causing retinal degeneration in seven N-ethyl-N-nitrosourea (ENU) induced mutant alleles of the Pde6b gene and to analyze the timescale of retinal degeneration in these new models of retinitis pigmentosa. METHODS:Conformation sensitive capillary electrophoresis and ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0254
更新日期:2005-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2018-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0392
更新日期:2004-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-1050
更新日期:2008-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2014-05-29 00:00:00
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更新日期:2014-09-16 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2007-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00