Abstract:
PURPOSE:To explore the role of integrin alpha5beta1 in proliferative vitreoretinopathy (PVR) pathogenesis by evaluating the expression alpha5beta1 on ARPE-19 cells and patient proliferative membranes, quantifying the inhibitory effects of JSM6427 (a small molecule alpha5beta1 inhibitor) on ARPE-19 cell adhesion and migration, and assessing the therapeutic potential of JSM6427 in a rabbit retinal detachment model. METHODS:Expression of alpha5beta1 was evaluated on activated ARPE-19 cells by flow cytometry and on PVR membranes by immunohistochemistry. ARPE-19 cells were used in fibronectin-dependent adhesion and migration assays with various concentrations of JSM6427; IC(50) was calculated. In the rabbit model, eyes were intravitreally injected with vehicle or JSM6427 on day 0 or 1 after retinal detachment; BrdU was administered intravitreally on day 3, and retinal tissues were harvested on day 3 (4 hours later) or 7. Retinal scarring, cellular proliferation, and inflammatory responses were quantified, and retinal morphology was analyzed in retinal sections. RESULTS:Activated ARPE-19 cells and PVR membranes expressed high levels of alpha5beta1; expression was low in control eyes. JSM6427 provided a dose-dependent blockade of ARPE-19 cell adhesion to fibronectin (IC(50), 7.1 +/- 2.5 microM) and inhibition of migration (IC(50), 6.0 +/- 4.5 microM). In the rabbit model, intravitreal injection of JSM6427 provided significant inhibition of proliferation of retinal cells (Müller cells, microglia, and macrophages) on days 3 and 7 after detachment and inhibition of inflammatory response and retinal scarring on day 7 after detachment. CONCLUSIONS:JSM6427 is a promising treatment for PVR, with data suggesting that inhibition of alpha5beta1-fibronectin interactions addresses multiple pathways involving retinal pigment epithelial, glial, and inflammatory cells.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Zahn G,Volk K,Lewis GP,Vossmeyer D,Stragies R,Heier JS,Daniel PE Jr,Adamis AP,Chapin EA,Fisher SK,Holz FG,Löffler KU,Knolle Jdoi
10.1167/iovs.09-3575subject
Has Abstractpub_date
2010-02-01 00:00:00pages
1028-35issue
2eissn
0146-0404issn
1552-5783pii
iovs.09-3575journal_volume
51pub_type
杂志文章abstract:PURPOSE:Organized conjunctiva-associated lymphoid tissue (O-CALT) is constantly exposed to environmental antigens and plays a central role in the common mucosal immune system. This study was undertaken to investigate whether O-CALT in rabbit lymphoid tissue, as in other lymphoid tissue in other mammals, changes with ag...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0856
更新日期:2008-02-01 00:00:00
abstract:PURPOSE:To determine protective properties of recombinant TCR ligands (RTLs) as a new treatment for experimental autoimmune anterior uveitis (AU). RTLs comprise the rat RT1.B beta1alpha1 domains, linked either to the guinea pig MBP69-89 peptide (RTL201), to the corresponding rat MBP69-89 peptide (RTL200), or to the car...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1242
更新日期:2006-06-01 00:00:00
abstract:PURPOSE:To determine whether messenger RNA coding for fibroblast growth factor receptor-1, interleukin-1 receptor, and glucocorticoid receptor messenger RNA are produced in human lacrimal tissue. METHODS:Total cellular RNA was isolated from three specimens of normal human lacrimal tissue and complementary DNA was synt...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract:PURPOSE:Angiogenesis, the formation of new capillary blood vessels, is an essential biological process under physiological conditions, including embryonic development, reproduction, and wound repair. Under pathologic conditions, this process plays a critical role in a variety of diseases such as cancer, rheumatoid arth...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-1527
更新日期:2008-09-01 00:00:00
abstract:PURPOSE:To characterize the chemokines and chemokine receptors that mediate the effect of proinflammatory cytokines, interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, on the recruitment of MHC class II(+) Langerhans cells (LCs) in the corneal epithelium. METHODS:A standard model for corneal LC recruitment, app...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0658
更新日期:2005-04-01 00:00:00
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 study transition zones from normal to abnormal retina in Usher syndrome IB (USH1B) caused by myosin 7A (MYO7A) mutations. METHODS:Optical coherence tomography (OCT) scattering layers in outer retina were segmented in patients (n = 16, ages 2-42; eight patients had serial data, average interval 4.5 years) to...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-18860
更新日期:2016-07-01 00:00:00
abstract:PURPOSE:To elucidate the spatial distribution of inactivation of lactate dehydrogenase (LDH) in ultraviolet-B radiation (UVR-B)-exposed eyes. To determine the in vivo penetration depth of UVR-B in the lens. METHODS:LDH activity in cornea and lens was investigated with an enzyme histochemical technique. Thirty rats wer...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract:PURPOSE:To investigate cytokine production by leukocytes in aqueous humor (AH) during corneal graft rejection and nitric oxide (NO) production by macrophages as a potential mediator of graft damage. METHODS:Rats received corneal allotransplants and were killed during acute rejection. Leukocytes in AH that expressed tu...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-1962
更新日期:2008-11-01 00:00:00
abstract:PURPOSE:Cigarette smoking is the most consistent risk factor for age-related macular degeneration (AMD), especially the choroidal neovascularization (CNV)-mediated exudative type. Dioxins and dioxin-like compounds have various effects on living organisms and are also contained in cigarette smoke. However, the effects o...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-2299
更新日期:2009-07-01 00:00:00
abstract:PURPOSE:To compare the prophylactic effects of intravenous moxifloxacin and vancomycin for Staphylococcus epidermidis endophthalmitis in a rabbit model. METHODS:Albino rabbits (n = 60) were divided into three groups. Intravenous moxifloxacin was injected into 20 animals (group 1), and intravenous vancomycin was inject...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5231
更新日期:2011-03-25 00:00:00
abstract:Purpose:To investigate the underlying mechanisms for how the mouse Cx50-R205G point mutation, a homologue of the human Cx50-R198W mutation that is linked to cataract-microcornea syndrome, affects proper lens growth and fiber cell differentiation to lead to severe lens phenotypes. Methods:EdU labeling, immunostaining, ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.3.25
更新日期:2020-03-09 00:00:00
abstract:Purpose:To compare cross-sectional choroidal morphology in rhesus macaque and human eyes using enhanced-depth imaging optical coherence tomography (EDI-OCT) and histologic analysis. Methods:Enhanced-depth imaging-OCT images from 25 rhesus macaque and 30 human eyes were evaluated for choriocapillaris and choroidal-scle...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-20070
更新日期:2016-10-01 00:00:00
abstract:PURPOSE:Amphibian retinas regenerate after injury, making them ideal for studying the mechanisms of retinal regeneration, but this leaves their value as models of retinal degeneration in question. The authors asked whether the initial cellular changes after rod loss in the regenerative model Xenopus laevis mimic those ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5347
更新日期:2011-01-21 00:00:00
abstract::Retinal dysplasia is a failure in normal retinal development. The morphologic sequence of the dysplastic processes was examined in fetuses and neonates from dogs affected with an inherited form of retinal dysplasia. The dysplastic change has its onset at 45-50 days' gestation and is most prominent in the dorsal peripa...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract:Purpose:The purpose of this work was to test whether palisade endings express structural and molecular features of exocytotic machinery, and are associated with acetylcholine receptors, and enzymes for neurotransmitter breakdown. Methods:Extraocular rectus muscles from six cats were studied. Whole-mount preparations o...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.14.31
更新日期:2020-12-01 00:00:00
abstract:PURPOSE:To test the hypothesis that retinal hypoxia is present during vascular development in normal rat pups and in a newborn rat model of retinopathy of prematurity (ROP). METHODS:Preretinal vitreous PO(2) measurements were made during room air breathing using (19)F magnetic resonance spectroscopy (MRS) and a perflu...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-1122
更新日期:2003-07-01 00:00:00
abstract:PURPOSE:Cultured human corneal endothelial cells (cHCECs) are anticipated to become an alternative to donor corneas for the treatment of corneal endothelial dysfunction. However, cHCECs reportedly tend to exhibit chromosomal abnormality during in vitro cell division, thereby hampering their use in the clinical setting....
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-19771
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:Previous studies have demonstrated a role for the retinal pigment epithelium (RPE) in the development and maintenance of the choroidal vasculature, suggesting that RPE serves a trophic role for the choroidal vessels. The goal of this study was to determine the expression pattern of vascular endothelial growth f...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1229
更新日期:2006-07-01 00:00:00
abstract::Ocular ultraviolet radiation (UVR) exposure was assessed in three occupational groups: fisherman, landscape workers and construction workers. The ratio of ocular exposure to ambient exposure was determined by placing UV-sensitive film (295-320 nm) between the eyes of the subjects and in a nearby open field. The mean o...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract:Purpose:Optical coherence tomography's (OCT) third outer retinal band has been attributed to the zone of interdigitation between RPE cells and cone outer segments. The purpose of this paper is to investigate the structure of this band with adaptive optics (AO)-OCT. Methods:Using AO-OCT, images were obtained from two s...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-21138
更新日期:2017-09-01 00:00:00
abstract:PURPOSE:Stereoscopic displays challenge the neural cross-coupling between accommodation and vergence by inducing a constant accommodative demand and a varying vergence demand. Stereoscopic viewing calls for a decrease in the gain of vergence accommodation, which is the accommodation caused by vergence, quantified by us...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-18854
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:This study was performed to investigate motion perception in patients with glaucoma. METHODS:A random dot motion test was used to measure three aspects of central motion perception: minimum displacement threshold (Dmin), maximum displacement threshold (Dmax), and coherence threshold (signal to noise). Motion p...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract:PURPOSE:To compare directly the robustness of standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), frequency-doubling perimetry (FDP), and grating-resolution perimetry (GRP) stimuli to different degrees of intraocular stray light induced by commercially available opacity-containing filters. ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-2934
更新日期:2009-08-01 00:00:00
abstract:PURPOSE:We tested the hypothesis that retinal blood flow has a postocclusive reactive hyperemia response modulated by occlusion duration and metabolic activity, and that choroidal blood flow does not. METHODS:Anesthetized and paralyzed rats (n = 34) were studied. Retinal and choroidal blood flow was measured by laser ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12404
更新日期:2013-07-30 00:00:00
abstract:Purpose:To determine if variation in anterior lamina cribrosa surface depth (ALCSD) differs between glaucoma patients of African (AD) and European descent (ED). Methods:A total of 178 eyes from 123 glaucoma patients in the African Descent and Glaucoma Evaluation Study (ADAGES) and Diagnostic Innovations in Glaucoma St...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.19-26645
更新日期:2019-10-01 00:00:00
abstract:PURPOSE:To evaluate the role of TIMP-1 in inherited retinal degeneration. METHODS:The genomic structure of the TIMP-1 gene was established and male patients with x-linked retinitis pigmentosa 2 from five families were screened for sequence alterations by direct sequencing in all exons, exon-intron boundaries, and the ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract:PURPOSE:The purpose of this study was to determine the feasibility of using Cerenkov luminescence imaging (CLI) to facilitate plaque placement during episcleral brachytherapy of intraocular tumors. METHODS:Ruthenium-106 (Ru-106) decays to rhodium-106, which in turn emits high-energy beta particles. When the electrons ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-18012
更新日期:2015-11-01 00:00:00
abstract:PURPOSE:To compare adult discrimination performance on nine pediatric visual acuity tests to determine the consistency of optotype design. METHODS:After their binocular acuity was measured with each test, eight adult observers (mean age, 27 years ± 6.3 SD; three emmetropes and five corrected myopes) were shown isolate...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6391
更新日期:2011-06-16 00:00:00
abstract:PURPOSE:To investigate a depolarizing layer that is visible in polarization-sensitive optical coherence tomography (PS-OCT) images of the retina. To identify this layer and characterize its depolarizing effect quantitatively. METHODS:Ten healthy human subjects (mean age, 31 +/- 8 years) and two patients with RPE disea...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1589
更新日期:2006-12-01 00:00:00