Abstract:
PURPOSE:To investigate the retinal-protective effects of the oral iron chelator deferiprone (DFP) in mice lacking the iron regulatory hormone hepcidin (Hepc). These Hepc knockout (KO) mice have age-dependent systemic and retinal iron accumulation leading to retinal degeneration. METHODS:Hepc KO mice were given DFP in drinking water from age 6 to 18 months. They were then compared to Hepc KO mice not receiving DFP by fundus imaging, electroretinography (ERG), histology, immunofluorescence, and quantitative PCR to investigate the protective effect of DFP against retinal and retinal pigment epithelial (RPE) degeneration. RESULTS:In Hepc KO mice, DFP diminished RPE depigmentation and autofluorescence on fundus imaging. Autofluorescence in the RPE layer in cryosections was significantly diminished by DFP, consistent with the fundus images. Immunolabeling with L-ferritin and transferrin receptor antibodies showed a decreased signal for L-ferritin in the inner retina and RPE cells and an increased signal for transferrin receptor in the inner retina, indicating diminished retinal iron levels with DFP treatment. Plastic sections showed that photoreceptor and RPE cells were well preserved in Hepc KO mice treated with DFP. Consistent with photoreceptor protection, the mRNA level of rhodopsin was significantly higher in retinas treated with DFP. The mRNA levels of oxidative stress-related genes heme oxygenase-1 and catalase were significantly lower in DFP-treated Hepc KO retinas. Finally, ERG rod a- and b- and cone b-wave amplitudes were significantly higher in DFP-treated mice. CONCLUSIONS:Long-term treatment with the oral iron chelator DFP diminished retinal and RPE iron levels and oxidative stress, providing significant protection against retinal degeneration caused by chronic systemic iron overload in Hepc KO mice. This indicates that iron chelation could be a long-term preventive treatment for retinal disease involving iron overload and oxidative stress.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Song D,Zhao L,Li Y,Hadziahmetovic M,Song Y,Connelly J,Spino M,Dunaief JLdoi
10.1167/iovs.14-14568subject
Has Abstractpub_date
2014-06-26 00:00:00pages
4525-32issue
7eissn
0146-0404issn
1552-5783pii
iovs.14-14568journal_volume
55pub_type
杂志文章abstract:PURPOSE:To study the antineoplastic effect of vitamin D analogues in a xenograft model of human retinoblastoma. METHODS:Athymic mice were injected subcutaneously with Y79 cells and treated 5 days a week with either mineral oil (control group) or the vitamin D analogues calcitriol or 1,25-dihydroxy-16-ene-23-yne vitami...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-1198
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abstract:PURPOSE:To characterize the prejunctional mechanisms that control the impulse-evoked release of norepinephrine in the isolated, superfused human iris-ciliary body. METHODS:Human iris-ciliary body tissue segments were preincubated with 3H-norepinephrine, superfused and electrically-stimulated in vitro to evoke the disc...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract:PURPOSE:To report the impact of intravitreous bevacizumab therapy on contrast sensitivity in patients with neovascular age-related macular degeneration (nAMD). METHODS:This was a prospective, multicenter, double-masked, randomized, controlled trial of 131 patients with nAMD. The patients with nAMD had received intravi...
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.10-6208
更新日期:2011-05-11 00:00:00
abstract:PURPOSE:The purpose of this study was to determine whether a better IOP reduction can be observed in conscious, normotensive monkeys treated with ONO-9054, a novel dual EP3 and FP receptor agonist, compared with prostaglandin F2α analogs. METHODS:The binding affinities and agonistic activities of ONO-AG-367, a carboxy...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-16181
更新日期:2015-04-01 00:00:00
abstract::Acute laser injury to the tapetum of the feline retina produces thrombosis of the choriocapillaris. Early changes are characterized by the appearance of platelet-fibrin thrombi within capillary loops and disruption of endothelial integrity. By 4 days, thrombi have disappeared, and the endothelium shows regenerative ch...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract:PURPOSE:The aim of this study was to elucidate the molecular mechanisms that lead to a dominant nuclear cataract in a mouse harboring the Y118D mutation in the alphaA-crystallin gene. METHODS:The physicochemical properties of alpha-crystallin obtained from mouse lenses with the Y118D mutation as well as a recombinant ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5334
更新日期:2010-09-01 00:00:00
abstract:PURPOSE:To study different aspects of macular function in eyes with early age-related macular degeneration (early AMD: drusen with or without retinal pigment epithelium alterations) and normal visual acuity, to obtain a complete evaluation of macular function impairment in early AMD and to study the relationship betwee...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract:PURPOSE:To evaluate a porcine anterior chamber perfusion model and to test the transferability of data obtained with this model to the human system. METHODS:Porcine eyes were obtained from a local abattoir and processed within 2 hours after death. Anterior chambers of 42 pairs of eyes were dissected with removal of le...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1393
更新日期:2006-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6908
更新日期:2011-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract:PURPOSE:To determine whether corneal acidosis, which occurs during contact lens wear, alters corneal O2 consumption (QO2) and if so, whether increased ion transport activity could contribute to altered QO2 during acidosis. METHODS:PO2 was measured, using the phosphorescence quenching of Pd-meso-tetra-(4-carboxyphenyl)...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract:Purpose:To compare blood pressure and urine albumin-creatinine ratio over time for participants receiving aflibercept, bevacizumab, or ranibizumab. Methods:Preplanned secondary analyses from a randomized trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME). The Diabetic Retinopath...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,随机对照试验
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更新日期:2018-03-01 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
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0403
更新日期:2006-11-01 00:00:00
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:
更新日期:1993-11-01 00:00:00
abstract:PURPOSE:The betaB2-crystallin gene (Crybb2) is expressed at an increasing level in the postnatal lens cortex. It has been assumed that the gene functions as structural protein, although this has not been directly tested. Here the in vivo functions of betaB2-crystallin are examined via the generation of mice with a targ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2008-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::Scanning electron microscopic (SEM) observations of the rabbit retinal pigment epithelium (RPE) are reported both for normal tissue and for tissue subjected to laser radiation. In normal RPE, cells were observed to be closely packed and to have the characteristic hexagonal shape. The microvilli were abundant and of tw...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1977-08-01 00:00:00
abstract:PURPOSE:To identify the mutation leading to syndromic choroideremia (CHM) in two families and to define fundus autofluorescence (FAF) in CHM carriers. METHODS:The ophthalmic and clinical phenotype was investigated including FAF, neuropediatric, otorhinolaryngologic, cardiologic, and nephrologic examinations of three m...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2013-10-09 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1979-08-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2010-08-01 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:2010-03-01 00:00:00
abstract:PURPOSE:To investigate whether the detection of apoptosing retinal cells (DARC) could detect cells undergoing apoptosis in a laser model of retinal damage. METHODS:Laser lesions were placed, with the use of a frequency-doubled Nd:YAG laser, on the retina in 34 eyes of anesthetized Dark Agouti rats. Lesion size and las...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2008-06-01 00:00:00
abstract:Purpose:To quantify the effect of induced stray light on halo size, luminance threshold, and contrast sensitivity. Methods:Retinal stray light was induced in five healthy subjects using different photographic filters. The stray light induced ranged from levels observed in intraocular lenses (IOLs) with glistenings (lo...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2016-10-01 00:00:00
abstract:PURPOSE:To estimate the critical duration of temporal summation for achromatic Goldmann III stimuli under the conditions of standard automated perimetry (SAP) and quantify response variability for short-duration stimuli. METHODS:Contrast thresholds were gathered using the method of constant stimuli for seven circular ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-15304
更新日期:2014-12-16 00:00:00
abstract:PURPOSE:Migration of Müller glial cells is enhanced in proliferative retinopathies, but the mechanisms involved are ill defined. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid synthesized by sphingosine kinase (SphK), which promotes proliferation, migration, and inflammation, acting as an intracellular media...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2015-09-01 00:00:00
abstract:PURPOSE:To compare the mydriatic effect and the short-term corneal endothelial safety of intracamerally injected N-methyl-3,4-dihydroxyphenylamine (epinine) to phenylephrine in a porcine eye model. METHODS:One hundred twelve eyes from newly slaughtered pigs were used in this study. After pretreatment with 20 mg intrac...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-3651
更新日期:2009-11-01 00:00:00
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
doi:10.1167/iovs.09-3764
更新日期:2009-12-01 00:00:00