Abstract:
PURPOSE:To test the hypothesis that overexpression of genes coding for the anti-apoptotic proteins Bcl-2 or Bcl-XL in photoreceptor cells may prevent or delay photoreceptor degenerations. METHODS:Transgenic mice were generated in which the bcl-2 or bcl-XL transgenes were expressed in photoreceptor cells under the transcriptional control of a rhodopsin gene promoter. Bcl-2 or bcl-XL transgenic mice were crossed separately to a mouse strain carrying the rd/rd mutation and to another mouse line carrying a dominant rhodopsin gene mutation; both genetic defects result in photoreceptor degeneration. Photoreceptor cell death in mice expressing one of the bcl transgenes and carrying either the rd mutation homozygously or the rhodopsin mutation heterozygously was examined by histologic and electroretinographic measurements. Bcl-2 and bcl-XL transgenic mice also were tested for possible resistance to light-induced photoreceptor damage under two different experimental conditions. RESULTS:Bcl-2 or bcl-XL transgenes were expressed in photoreceptor cells of all lines of transgenic mice. In both the rd and the rhodopsin mutant mice, expression of either bcl-2 or bcl-XL transgenes did not prevent or measurably delay photoreceptor degeneration. Apoptosis-related nuclear DNA fragmentation, as assessed by in situ labeling with terminal deoxynucleotidyl transferase, was present in 13-day-old rd/rd mouse retinas with or without transgene expression. Twelve days after exposure to 2 hours of high-intensity light, bcl-2 transgenic mice retained approximately four rows of photoreceptor cells in the central retina as compared to none in littermate controls, whereas bcl-XL transgenic mice showed no increased resistance to light damage. Expression of the bcl-2 but not the bcl-XL transgene also was associated with a reduction in rhodopsin content. CONCLUSIONS:Overexpression of bcl-2 or bcl-XL transgenes does not rescue photoreceptor cells from apoptosis caused by the two genetic mutations tested. Resistance to light damage seen in the bcl-2 transgenic mice is likely from a reduction in rhodopsin content rather than an anti-cell death activity of Bcl-2. Cell death pathways not regulated by Bcl-2 may be operative in photoreceptor degeneration.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Joseph RM,Li Tsubject
Has Abstractpub_date
1996-11-01 00:00:00pages
2434-46issue
12eissn
0146-0404issn
1552-5783journal_volume
37pub_type
杂志文章abstract:PURPOSE:Phakic intraocular lenses (pIOLs) are used for correcting vision; in this paper we investigate the fluid dynamical effects of an iris-fixated lens in the anterior chamber. In particular, we focus on changes in the wall shear stress (WSS) on the cornea and iris, which could be responsible for endothelial and pig...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-16118
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:Diabetic retinopathy (DR) is a leading cause of blindness, yet pertinent animal models are uncommon. The sand rat (Psammomys obesus), exhibiting diet-induced metabolic syndrome, might constitute a relevant model. METHODS:Adult P. obesus (n = 39) were maintained in captivity for 4 to 7 months and fed either veg...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8423
更新日期:2011-11-21 00:00:00
abstract:PURPOSE:A pilot study of human neural retinal transplantation was undertaken to investigate three major issues: whether a safe surgical procedure could be devised for transplantation of neural retinal tissue into the subretinal space, whether the transplant would be accepted in the subretinal space, and whether an impr...
journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:PURPOSE:To determine the effect of triamcinolone acetonide (TA) on outflow facility in mice. METHODS:Animals received 20 μL of TA (40 mg/mL) suspension subconjunctivally either bilaterally or unilaterally and were euthanized after either 1 week or 3 weeks. Before mice were killed, IOP was measured with a rebound tonom...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-11223
更新日期:2013-02-01 00:00:00
abstract::This study demonstrated that growth and differentiation of rabbit conjunctival epithelial cells could be promoted by such substrata as collagen gel, matrigel or various mixtures of collagen and matrigel in a defined culture system. On conventional plastic or glass culture, the conjunctival epithelial cells adopted a m...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract:PURPOSE:To quantify protein changes in the morphologically distinct remodeling zone (RZ) and adjacent regions of the human lens outer cortex using spatially directed quantitative proteomics. METHODS:Lightly fixed human lens sections were deparaffinized and membranes labeled with fluorescent wheat germ agglutinin (WGA-...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-19791
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:To explore the maximum retinal vasodilation in response to repeated flicker light stimulation in relation to vasospastic propensity in healthy subjects. METHODS:Twenty-four young healthy women were grouped as vasospastic and nonvasospastic, based on their history of cold extremities and on the results of nailf...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0351
更新日期:2006-09-01 00:00:00
abstract::Pattern ERGs in response to pattern-reversal stimuli varying in spatial frequency (range: 0.2-9.03 cycles/deg) and contrast (range: 0.03-0.93) were recorded from two normal male subjects. At most spatial frequencies the response amplitude increased linearly up to the highest contrast without saturation. From the ampli...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Wound healing in the eye may lead to undesirable sequelae such as proliferative vitreoretinopathy and scarring of glaucoma filtering fistulas. We therefore sought to manipulate in vitro two key wound healing processes--cell proliferation and contraction of extracellular matrices--using vitamin A (VA), retinoic acid (R...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Sixteen patients with osteogenesis imperfecta (OI) have undergone a thorough eye examination. These patients had statistically significantly lower ocular rigidity measurements than a group of normal volunteers matched on age, sex, and refractive error. In addition, the corneal diameter and length of the eyeball was sm...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract:Purpose:The purpose of this study was to measure change in anterior lamina cribrosa depth (ALD) globally and regionally in glaucoma eyes at different intraocular pressures (IOP). Methods:Twenty-seven glaucoma patients were imaged before and after IOP-lowering procedures using optical coherence tomography. The anterior...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-21321
更新日期:2017-05-01 00:00:00
abstract:PURPOSE:Tissues derived from immune-privileged sites sometimes possess special characteristics that promote their own survival when transplanted to a nonprivileged site. This study was undertaken to evaluate whether retinal pigment epithelium (RPE) behaves as an immune-privileged tissue when transplanted extraocularly....
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 investigate the regulatory role of FGF-2 on type I collagen expression during endothelial mesenchymal transformation (EMT). METHODS:Corneal endothelial cells (CECs) treated with FGF-2 from the primary culture to the third passage were transformed and designated as fibroblastic CECs (fCECs). Steady state lev...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0818
更新日期:2005-12-01 00:00:00
abstract:PURPOSE:To characterize the cellular expression patterns of antiangiogenic factors differentially regulated in the fetal human macula. METHODS:RNA was extracted from macular, nasal, and surround biopsies of three human fetal retinas at midgestation. Relative levels of expression of pigment epithelium-derived factor (P...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4905
更新日期:2010-08-01 00:00:00
abstract:PURPOSE:To determine the effects of silicone hydrogel lens wear and lens-solution interactions on ocular surface sensitivity. METHODS:Forty-eight adapted lens wearers completed the study, which comprised two phases. Phase 1 included habitual lens wear, no lens wear (7 ± 3 days), and balafilcon A lenses (PV; PureVision...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,随机对照试验
doi:10.1167/iovs.09-4807
更新日期:2010-12-01 00:00:00
abstract::Cyclodestructive modalities in humans have been shown to be effective when applied 3.5 mm or more posterior to the limbus. Therefore, CW Nd:YAG contact transscleral laser and cryopexy were applied 6 mm posterior to the limbus of pigmented rabbits. The intraocular pressure (IOP), flare, iritis, cells and conjunctival h...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract:PURPOSE:To determine whether the human retinal oxygenation response (deltaPO2) to a hyperoxic provocation is abnormal in patients with type I diabetes. METHODS:Magnetic resonance imaging (MRI) was used to measure deltaPO2 during 100% oxygen breathing in patients with type I diabetes who had either no clinically detect...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0833
更新日期:2006-04-01 00:00:00
abstract::The acute effect of topical epinephrine HCl 2% on macular capillary blood flow was studied in 18 healthy human volunteers using the blue-field simulation technique. This technique provides a method for quantifying the velocity of leukocytes flowing in macular capillaries. Subjects adjusted the velocity of simulated le...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
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
更新日期:2018-03-01 00:00:00
abstract:PURPOSE:In glaucoma, the optic nerve head (ONH) is the principal site of initial axonal injury, and elevated intraocular pressure (IOP) is the predominant risk factor. However, the initial responses of the ONH to elevated IOP are unknown. Here the authors use a rat glaucoma model to characterize ONH gene expression cha...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5317
更新日期:2011-01-25 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) inoculated directly into the anterior chamber of the mouse eye induced an acute inflammatory process in both the injected eye and its uninjected (contralateral) counterpart. In the former, a rapid intense inflammatory reaction developed in the anterior segment (cornea, anterior cham...
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:Retinal ganglion cells are known to express ionotropic P2X(7) receptors for ATP. Stimulation of these receptors in other cells can elevate Ca(2+) and sometimes lead to cell death. This study asked whether P2X(7) receptor stimulation alters the Ca(2+) levels and viability of retinal ganglion cells. METHODS:P2X(...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0052
更新日期:2005-06-01 00:00:00
abstract:PURPOSE:Histone lysine methylation (HKM) is an important epigenetic mechanism that establishes cell-specific gene expression and functions in development. However, epigenetic control of retinal development is poorly understood. To study the roles of HKM in retinogenesis, the authors examined the dynamic changes of thre...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4730
更新日期:2010-12-01 00:00:00
abstract:PURPOSE:To investigate the expression of humanin (HN) in human retinal pigment epithelial (hRPE) cells and its effect on oxidative stress-induced cell death, mitochondrial bioenergetics, and senescence. METHODS:Humanin localization in RPE cells and polarized RPE monolayers was assessed by confocal microscopy. Human RP...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-17053
更新日期:2016-03-01 00:00:00
abstract:PURPOSE:To determine the usefulness of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the identification and speciation of bacteria causing endophthalmitis. METHODS:PCR-RFLP was performed on 53 strains of 14 bacterial species (eight Gram positive and five Gram negative) collected from...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract:PURPOSE:Metabolism and transport of glutathione (GSH), the endogenous thiol antioxidant, in conjunctival tissue to date are poorly understood. The purpose of the present study was to define transport characteristics of GSH in primary cultured rabbit conjunctival epithelial cells (RCECs). METHODS:RCECs were grown on me...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract:PURPOSE:Endotoxin-induced uveitis (EIU) is a model that mimics human acute anterior uveitis. Cyclooxygenase (COX)-2 is an enzyme that initiates the conversion of arachidonic acid (AA) into prostaglandins (PGs), whereas 5-lipoxygenase (5-LO) generates leukotrienes (LT). The purpose of this study was to delineate the rol...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0756
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:This study explores the order of assembly of the lens fiber cell plasma membrane. Because the lens must synthesize most of its membrane components, our approach was to map directly the spatial distribution of cholesterol, fatty acid (reflecting phospholipid), and the main intrinsic protein, MP26, synthesis in t...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract:PURPOSE:The aim of this study was to demonstrate the synthesis and cellular distribution of group II phospholipase A2 and lysozyme in the main and accessory lacrimal glands. METHODS:The authors studied samples of normal main lacrimal glands of seven autopsied subjects and accessory lacrimal glands of eight patients wh...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract:PURPOSE:The purpose of this study was to investigate the mutational incidence and spectrum of mitochondrial ND1 gene in subjects with Leber's hereditary optic neuropathy (LHON). METHODS:A cohort of 1281 Han Chinese probands and 478 control subjects underwent sequence analysis of mitochondrial (mt)DNA. Resultant varian...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:10.1167/iovs.16-19243
更新日期:2016-05-01 00:00:00