Abstract：
PURPOSE:To analyze whether insulin receptor substrate (IRS-1) is involved in lymphatic vessel development and whether IRS-1 blockade can inhibit lymphangiogenesis in vivo. METHODS:The impact of IRS-1 blockade by GS-101 (Aganirsen), an antisense oligonucleotide against IRS-1, on lymphatic endothelial cell (LEC) proliferation was assessed by ELISA. Furthermore, the effect of IRS-1 blockade on prolymphangiogenic growth factor expression by LECs and macrophages (peritoneal exudate cells) was tested by real-time PCR. The mouse model of inflammatory corneal neovascularization was used to analyze the effect of IRS-1 blockade in vivo: after corneal suture placement, mice were treated with GS-101 eye drops (twice daily afterwards for 1 week, 5 μL per drop; 50, 100, or 200 μM). Afterward, corneal wholemounts were prepared and stained for blood and lymphatic vessels. RESULTS:Blockade of IRS-1 by GS-101 inhibited LEC proliferation dose dependently. GS-101 led to decreased VEGF-A expression levels in LECs, whereas VEGF-C, VEGF-D, and VEGFR3 showed no significant change. In macrophages, VEGF-A expression levels were also inhibited by IRS-1 blockade. Additionally, GS-101 strongly inhibited macrophage-derived VEGF-C, VEGF-D, and VEGFR3 expression. In vivo, corneal hemangiogenesis was significantly inhibited when used at a concentration of 200 μM (by 17%; P < 0.01). Corneal lymphangiogenesis was significantly inhibited when used at a dose of 100 μM (by 21%; P < 0.01), and the highest used dose (200 μM) showed an even stronger inhibition (by 28%; P < 0.001). CONCLUSIONS:Blockade of IRS-1 inhibits not only hemangiogenesis but also lymphangiogenesis. To the authors' knowledge, this is the first evidence that IRS-1 is involved in the molecular pathway leading to lymphangiogenesis.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Hos D,Regenfuss B,Bock F,Onderka J,Cursiefen Cdoi
10.1167/iovs.10-6816subject
Has Abstractpub_date
2011-07-29 00:00:00pages
5778-85issue
8eissn
0146-0404issn
1552-5783pii
iovs.10-6816journal_volume
52pub_type
杂志文章abstract：PURPOSE:To study reading acuity in children and assess the reliability of its measurement using the Italian version of the MNREAD reading chart. METHODS:One hundred sixteen children from grades 3 to 8 with normal near vision were tested at a pediatric eye care institution in northeastern Italy. Visual acuity was evalu...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.03-1304
更新日期：2004-09-01 00:00:00
abstract：PURPOSE:Varicella zoster virus (VZV) is a common cause of infectious uveitis associated with an intraocular inflammatory response involving virus-specific T cells. In the current study, the functional characteristics and the antigen specificity of VZV-reactive T cells recovered from intraocular fluid (IOF) samples of f...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-0020
更新日期：2007-08-01 00:00:00
abstract：PURPOSE:Oxidative stress in the human lens leads to a wide range of damage including DNA strand breaks, which are likely to contribute to cataract formation. The protein Ku80 is a fundamental component of the nonhomologous end-joining pathway that repairs DNA double strand breaks. This study investigates the putative i...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.15-18309
更新日期：2015-12-01 00:00:00
abstract：PURPOSE:Lacritin is a tear glycoprotein with prosecretory, prosurvival, and mitogenic properties. We examined lacritin levels in the tears of Sjögren's syndrome (SS) patients and explored the therapeutic potential of topical lacritin for the treatment of keratoconjunctivitis sicca. METHODS:Tears from healthy controls ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.14-13924
更新日期：2014-07-17 00:00:00
abstract：:Chinese hamster ovarian (CHO) cells in culture were used to evaluate the relative antiproliferative potential of drugs. These agents have been used to improve the clinical response after glaucoma filtering surgery. The following drugs were evaluated: 5-fluorouracil (5-FU) as the benchmark, 5-fluorouridine (FUR), 5-flu...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：PURPOSE:Subcellular Ca2+ signaling patterns, such as Ca2+ waves, gradients, and oscillations, are an important aspect of cell regulation, but the molecular basis for these signaling patterns is not understood. Because Ca2+ release patterns differ among isoforms of the inositol 1,4,5-trisphosphate (InsP3) receptor, the ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1999-08-01 00:00:00
abstract：PURPOSE:Elevated levels of extracellular glutamate have been implicated in the pathophysiology of neuronal loss in both central nervous system and ophthalmic disorders, including glaucoma. This increase in glutamate may result from a failure of glutamate transporters (molecules that ordinarily regulate extracellular gl...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
abstract：:Spleen cells of BALB/c mice, previously immunized with bovine retinal S-antigen, were fused with Sp2/0-Ag14 mouse myeloma cells. Two monoclonal antibodies (MAbs) MAbA9-C6 (IgG2a isotype) and MAbA1-G5 (IgG1 isotype) were selected on the basis of reactivity in an ELISA and immunofluorescent assay. In radioimmunoassay MA...
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:As efforts to noninvasively measure intracranial pressure (ICP) increase, we thought it important to investigate the timing of retinal venous pulsation in relation to the intraocular and intracranial pressure pulses. METHODS:Neurosurgical patients undergoing continuous direct ICP monitoring had video recording...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-9837
更新日期：2012-07-10 00:00:00
abstract：PURPOSE:CD40 antigen is a membrane receptor that plays a role in the regulation of immune reactions. The expressions of CD40 and CD40 ligand (CD40L) were investigated ex vivo and in vitro in conjunctival epithelial cells, in correlation with HLA DR class H antigen, previously shown to be upregulated in conjunctival inf...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2000-01-01 00:00:00
abstract：PURPOSE:To determine if there is endothelin-mediated regulation of cell signaling and proliferation in rabbit corneal epithelium. METHODS:Endothelin-1 (ET-1) gene and protein expression by the rabbit corneal epithelial (RCE) cells were analyzed by polymerase chain reaction, sequence analysis, and enzyme immunoassay. D...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：PURPOSE:To characterize the response of cultured human retinal pigment epithelial (RPE) cells to lowered environmental oxygen. METHODS:The response of cultured RPE cells to lowered oxygen environments was compared to that of cell types of presumed high (Madin-Darby canine kidney [MDCK] cells, an epithelial cell line) ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：PURPOSE:A relationship has been reported between the presence of peripheral neuropathy and the density and shape of corneal nerve fibers. Peripheral neuropathy is a debilitating condition that arises from many common health problems, and its presence is often confirmed with an invasive clinical test called intramuscula...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.09-4108
更新日期：2010-09-01 00:00:00
abstract：:The retinas of six pigmented rabbits (12 eyes) were irradiated with a cw-Nd:YAG laser using two different pulse forms, in conjunction with a constant pulse duration of 200 msec and a retinal focus diameter of 200 microns. The first pulse form (a) was characterized by an initial transient, lasting 15-20 msec, with a pe...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:To determine whether ciliary body thickness (CBT) is related to refractive error in school-age children. METHODS:Fifty-three children, 8 to 15 years of age, were recruited. CBT was measured from anterior segment OCT images (Visante; Carl Zeiss Meditec, Inc., Dublin, CA) at 1 (CBT1), 2 (CBT2) and 3 (CBT3) mm po...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.08-2008
更新日期：2008-10-01 00:00:00
abstract：Purpose:Although normal function of the lacrimal gland is essential for vision (and thus for human well-being), the lacrimal gland remains rather poorly understood at a molecular level. The purpose of this study was to identify new genes and signaling cascades involved in lacrimal gland development. Methods:To identif...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.16-20315
更新日期：2017-02-01 00:00:00
abstract：:In tear fluid, a large number of proteins can be detected with electrophoretic or immunologic techniques. The composition of serum proteins in tears resembles that of whole serum. By comparison of the protein patterns resulting from different sampling methods, it was shown that serum albumin is not present in the secr...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:In the retina from an eye enucleated for choroidal melanoma apposed rod outer segments were seen by transmission electron microscopy to be fusing together in groups by the confluence of their plasma membranes and the formation of cytoplasmic bridges between adjacent outer segments. These fusions were seen in areas dis...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1977-07-01 00:00:00
abstract：PURPOSE:To characterize the phagocytosis of extracellular matrix components by retinal pigment epithelial cells and to determine which receptors and signal transduction pathways are involved. METHODS:Fluorescent latex beads were coated with fibronectin (FN), collagen type I or IV, or thrombospondin and incubated with ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：PURPOSE:To characterize the differential expression of intraocular inflammatory cytokines in eyes with branch retinal vein occlusion (BRVO) and to assess their roles as prognostic determinants of BRVO. METHODS:A prospective cohort study of 38 eyes with BRVO. Aqueous humor samples were collected just before the intravi...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.10-6299
更新日期：2011-05-06 00:00:00
abstract：PURPOSE:To determine the association between ocular dominance and spherical or astigmatic anisometropia, age, and sex. METHODS:Medical records of 10,264 myopic refractive surgery candidates were filtered. Ocular dominance was assessed with the hole-in-the-card test. Manifest refractive error was measured in each subje...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-8131
更新日期：2011-11-25 00:00:00
abstract：PURPOSE:To assess the impact of glaucoma-related vision loss on measures of out-loud reading, including time to say individual words, interval time between consecutive words, lexical errors, skipped words, and repetitions. METHODS:Glaucoma subjects (n = 63) with bilateral visual field loss and glaucoma suspect control...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.15-15462
更新日期：2015-03-03 00:00:00
abstract：:Topical administration of biosynthetic human epidermal growth factor (h-EGF), given in combination with an antibiotic and synthetic steroid (Neodecadron) accelerated the rate of corneal epithelial regeneration and significantly increased the strength of full-thickness stromal incisions in primates. The regenerated epi...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：PURPOSE:To describe the evolution of retinal thickness in eyes affected with acute anterior uveitis (AAU) in the course of follow-up and to assess its correlation with severity of inflammatory activity in the anterior chamber. METHODS:72 eyes (affected and fellow eyes) of 36 patients presenting with HLA-B27-related ac...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-10026
更新日期：2012-09-14 00:00:00
abstract：:Alloantigens placed into the anterior chamber of the eye elicit antigen-specific suppression of systemic delayed-type hypersensitivity (DTH) responses and severe impairment of skin allograft rejection. This pattern of immunologic alteration has been termed anterior chamber-associated immune deviation (ACAID) and is th...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：PURPOSE:To determine the role of connexin43 (Cx43) and gap junctional intercellular communication (GJIC) in the response of the human retinal pigment epithelial cell line ARPE-19 to oxidative stress. METHODS:ARPE-19 cells were treated with the chemical oxidant tert-butyl hydroperoxide (t-BOOH), and cell viability was ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-0717
更新日期：2008-02-01 00:00:00
abstract：Purpose:To assess the phenotypic variability and natural course of inherited retinal diseases (IRDs) caused by EYS mutations. Methods:Multiethnic cohort study (N = 30) with biallelic EYS variants from a clinical IRD database (retinitis pigmentosa [RP], N = 27; cone-rod dystrophy [CRD], N = 1; and macular dystrophy, N ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章,多中心研究
doi：10.1167/iovs.18-25531
更新日期：2019-05-01 00:00:00
abstract：PURPOSE:To investigate the choroidal thickness (CT) in children with amblyopia through spectral-domain optical coherence tomography (SD-OCT). METHODS:Thirty-seven children with unilateral amblyopia and 22 children with normal vision participated in the study. Cross-sectional images of the choroid of evaluated eyes wer...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.14-14439
更新日期：2014-10-14 00:00:00
abstract：:Cataracts in cultured rabbit lenses were produced by elevation of internal calcium. Experimental procedures were successful in increasing levels of total and bound Ca++, often without significant changes in sodium, potassium, or water content. Although the excess in calcium was predominantly associated with water-solu...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1982-02-01 00:00:00
abstract：:Effects of substance P (SP) and vasoactive intestinal peptide (VIP) on motor function of bovine sphincter, dilator, and ciliary muscles were investigated pharmacologically, with and without field stimulation. SP contracted the sphincter and the maximum response was only about 25% of that in the presence of equimolar d...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1983-12-01 00:00:00
