Abstract:
PURPOSE:The primary purpose of this study was to characterize photoreceptor apoptosis in the rd mouse. Given that apoptosis is the final common pathway in many cases of retinal degeneration, the ability to retard or even arrest this process may ameliorate retinal disorders such as retinitis pigmentosa (RP). The absence of any recognized therapy emphasizes the fact that a detailed knowledge of the molecular events involved is necessary to identify rational targets for therapeutic intervention. METHODS:Flow cytometry was used to measure physical and chemical characteristics in the photoreceptor population. Individual cells flow in suspension past one or more lasers, scattering light and emitting fluorescence. Western blot techniques demonstrated cleavage of calpain-specific substrates. Retinal explant cultures were used for inhibitor studies. Postnatal day 10 (P(10)) rd retinas were cultured without retinal pigment epithelium (RPE) attached up to P(17). RESULTS:This study demonstrated calcium overload in the cytosol and subsequently in mitochondria. Mitochondrial membrane depolarization and reactive oxygen species (ROS) were detected later, during the peak of cell death. Analysis of downstream events indicated early activation of calcium-activated calpains. Treatment of rd retinal explants with the calpain inhibitor N-acetyl-Leu-Leu-Nle-CHO (ALLN) successfully inhibited calpain-induced alpha-fodrin cleavage, yet it did not protect against photoreceptor degeneration. Finally, the results demonstrate an increase in the levels of both precursor and processed forms of the aspartate protease cathepsin D. CONCLUSIONS:Excessive calcium influx is an early event that initiates the activation of calcium-activated proteases. However, these proteases are not singularly the cause of death, because their inhibition does not prevent apoptosis. Indeed, the results presented herein suggest that multiple pathways are involved and that each of these components may have to be addressed for cell death to be successfully inhibited.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Doonan F,Donovan M,Cotter TGdoi
10.1167/iovs.05-0248keywords:
subject
Has Abstractpub_date
2005-10-01 00:00:00pages
3530-8issue
10eissn
0146-0404issn
1552-5783pii
46/10/3530journal_volume
46pub_type
杂志文章abstract:Purpose:We describe the spatial distribution and cross-sectional associations with physical and lifestyle attributes. Methods:The participants of the Montrachet (Maculopathy Optic Nerve, nuTRition neurovAsCular and HEarT) study underwent an exhaustive ophthalmologic examination, including optical coherence tomography,...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:10.1167/iovs.16-19958
更新日期:2016-08-01 00:00:00
abstract::The unscarified corneas of rabbits were inoculated with 50 microliter of 2-4 X 10(6) PFU/ml of herpes simplex virus, type 1 (HSV-1), McKrae strain in 10 separate experiments over a 12-month period. Sixty of 104 (57.7%) rabbits survived to postinoculation (PI) day 20. These sixty rabbits were swabbed with dacron-tipped...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1985-04-01 00:00:00
abstract:Purpose:The purpose of this study was to evaluate the efficacy of new viscous cysteamine hydrochloride (CH) eye drops (vCH 0.55%) compared with standard CH 0.10% drops treatment. Methods:This was an open-label, phase III, randomized, two-arm multicenter trial conducted at two centers in France. Cystinosis patients ≥2 ...
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.16-21080
更新日期:2017-04-01 00:00:00
abstract:PURPOSE:To determine the contribution of copy number variation (CNV) in glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) to the susceptibility to age-related cataract (ARC) and its subtypes in a Han Chinese population. METHODS:ARC cases (n = 279) and controls (n = 145) were included from a...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5240
更新日期:2010-08-01 00:00:00
abstract:PURPOSE:Allopregnanolone is a neurosteroid and powerful modulator of neuronal excitability. The neuroprotective effects of allopregnanolone involve potentiation of γ-aminobutyric acid (GABA) inhibitory responses. Although glutamate excitotoxicity contributes to ganglion cell death in glaucoma, the role of GABA in glauc...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-15624
更新日期:2014-11-18 00:00:00
abstract::Inoculation of the neurotropic coronavirus mouse hepatitis virus strain JHM intravitreally or into the anterior chamber causes acute infection of the retinal pigment epithelium (RPE) and neural retina. Weeks later, many retinas have foci of moderate to severe atrophy. The effect of coronavirus infection (after intravi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::The effects of x-rays and three chemical agents, known to cause intraocular inflammation in mammalian eyes, were studied on the chicken eye because this species was reported to be insensitive to the cataractogenic effects of x-rays. Intravitreal injection of Shigella endotoxin and topical and/or intravitreal administr...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1978-05-01 00:00:00
abstract:PURPOSE:To evaluate the pharmacokinetics of ciliary neurotrophic factor (CNTF) delivered over a period of up to 2 years by an intraocular encapsulated cell technology (ECT) implant in patients with retinitis pigmentosa (RP) and geographic atrophy (GA). METHODS:Patients from phase 1 RP (CNTF1); phase 2 GA (CNTF2); and ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2012-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-2499
更新日期:2009-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-7174
更新日期:2011-07-18 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.6.2
更新日期:2020-06-03 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-3202
更新日期:2009-07-01 00:00:00
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
doi:10.1167/iovs.11-7210
更新日期:2011-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-1210
更新日期:2008-08-01 00:00:00
abstract::The first heritable model of retinoblastoma was established by retina-specific expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice. Bilateral, multifocal ocular tumors were observed in 100% of transgene-bearing mice. Central nervous system neoplasms occurred at a lower rate (27%) and represented the...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract:Purpose:Synthesis of keratan sulfate (KS) relies on coordinated action of multiple enzymes, including the N-acetylglucosamine-transferring enzyme, β-1,3-N-acetylglucosaminyltransferase-7 (β3GnT7). A mouse model deficient in β3GnT7 was developed to explore structural changes in KS and the extracellular matrix (ECM; i.e....
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-22716
更新日期:2018-03-01 00:00:00
abstract::A method for assessing the inward permeability of the blood-retinal barrier by fluorophotometry is presented. The permeability value is calculated with the fluorophotometer computer from fluorophotometric scan values in vitreous and non-protein-bound fluorescein concentration values in plasma. No diffusion coefficient...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract:PURPOSE:Leber congenital amaurosis (LCA) is a group of childhood-onset retinal diseases characterized by severe visual impairment or blindness. One form is caused by mutations in the RPE65 gene, which encodes the retinal pigment epithelium (RPE) isomerase. In this study, the retinal structure and expression of molecula...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5213
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:
更新日期:2000-12-01 00:00:00
abstract::Swollen rabbit corneas incubated in vitro with their posterior surfaces blocked with silicone oil maintained fairly constant thickness over an 11 hr. period. Increasing the simulated intraocular pressure from 10 to 30 mm. Hg did not produce stromal thinning. When theophylline was added to stimulate epithelial Cl secre...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1977-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章
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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:
更新日期:2000-03-01 00:00:00
abstract:PURPOSE:To test whether eliprodil (SL 82.0715), a unique antagonist for the N-methyl-D-aspartate (NMDA) receptor, is protective in the glutamate-induced cytotoxicity model in cultured rat retinal ganglion cells (RGCs). METHODS:Two to four days after a fluorescent dye, Di-I, was injected near the superior colliculi, ne...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::Eight murine monoclonal antibodies to retinal S-antigen were found to recognize three antigenic clusters in competitive binding experiments. Variable patterns of immunohistochemical staining of retinal sections supported the competitive binding studies. Monoclonal antibodies to two of these three antigenic clusters on...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Ultrastructural cytochemistry was used to localize a previously undescribed retinal enzyme activity, ie, "manganese-dependent pyrimidine 5'-nucleotidase" (MDPNase) activity in retinas from rats raised in cyclic light and killed at various times in the lighting cycle. In retinas fixed during the last 3 hr of darkness, ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1192
更新日期:2006-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.18-24206
更新日期:2018-08-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
abstract:PURPOSE:To evaluate by vector analysis the corneal astigmatic changes occurring in keratoconic corneas during a 3-year follow-up and to determine the relationship between these changes and other clinical changes. METHODS:Keratoconic eyes (n = 114) of 75 patients ranging in age from 14 to 70 years were retrospectively ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:10.1167/iovs.10-6856
更新日期:2011-06-08 00:00:00