Abstract：
:The aim of this study was to test the selectivity, in-vivo effectiveness, and potential mechanism of action of a linomide analogue (N-phenyl-1,2-dihydro-4-hydroxyl-2-oxo-quinoline-3-carboxamide, Lin05) for inhibition of choroidal neovascularization. The selectivity of Lin05 was tested in cell proliferation assays with human umbilical vein endothelial cells (HUVEC) and a retinal pigmented epithelial cell line(ARPE-19). In-vivo anti-angiogenic effect of Lin05 was investigated utilizing an experimental laser-induced choroidal neovascularization (ECNV) model in adult Brown Norway rats. Western blot and/or reverse transcriptase-PCR was used to test the effect of Lin05 on potential targets. Our results indicate that Lin05 is at least an 8-fold more selective inhibitor of endothelial cell proliferation compared to RPE cells. Systemic administration of Lin05 in an ECNV model was associated with a significant decrease in both vascular leakage on fluorescein angiography and lesion size by histopathology (p = 0.02). No systemic toxicity was detected for Lin05 in major organs such as the liver, lung and kidneys. Lin05 did not inhibit VEGF-induced VEGFR2 (KDR) phosphorylation in HUVEC nor was associated with decreased VEGF gene expression. Also it did not inhibit insulin-like growth factor (IGF-1) and Epidermal Growth Factor (EGF) induced activation of p42/p44 MAPK activation. It inhibited both PDGF- and bFGF-induced p42/p44 MAPK phosphorylation. However, the effect on PDGF was variable in different HUVEC cells. In conclusion, Lin05 is a potential anti-angiogenic agent for the treatment of eye diseases associated with pathological neovascularization. The anti-angiogenic effect of Lin05 is likely through inhibition of bFGF but not through inhibition of the VEGF/KDR pathway.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Abdel-Rahman MH,Yang Y,Salem MM,Meadows S,Massengill JB,Li PK,Davidorf FHdoi
10.1016/j.exer.2010.10.013subject
Has Abstractpub_date
2010-12-01 00:00:00pages
837-43issue
6eissn
0014-4835issn
1096-0007pii
S0014-4835(10)00336-2journal_volume
91pub_type
杂志文章abstract：:In our earlier study we showed that invasive retinoblastoma (RB) had down regulated tetraspanin protein KAI1/CD82, a family of cell surface glycoprotein. KAI1 may link to the cell surface molecules, such as integrins, E-cadherin, and other TM4SF members, and loss of KAI1 function may have a significant role in the pro...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.06.014
更新日期：2007-04-01 00:00:00
abstract：:We sought to determine the effects of exogenous epidermal growth factor (EGF), heparin-binding EGF (HB-EGF), transforming growth factor alpha (TGF-alpha), single-chain precursor hepatocyte growth factor (SC-HGF), double-chain mature HGF (DC-HGF), and keratinocyte growth factor (KGF) on proliferation, motility, and dif...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1994.1152
更新日期：1994-12-01 00:00:00
abstract：:The aim of this study was to elucidate the expression of chemokines, their role and regulation in bacterial corneal infection using three bacterial strains (Pseudomonas. aeruginosa- invasive, cytotoxic and contact lens induced acute red eye strains) which have been shown to produce three distinct patterns of corneal d...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(02)00270-1
更新日期：2003-02-01 00:00:00
abstract：:Cynomolgus (Macaca fascicularis) monkeys from three families, which showed symptoms of early onset macular degeneration was studied. Two proteins, albumin and glyceraldehyde 3-phosphate dehydrogenase, were found to have markedly altered concentrations in whole retina of the monkeys with early onset macular degeneratio...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1996.0026
更新日期：1996-03-01 00:00:00
abstract：:Although primary cultures of human lens epithelial (HLE) cells provide important information concerning the role of epithelium in normal lens and cataract formation, the lack of a cell line precludes a broad range of studies on the metabolism and molecular biology of these cells. We have, therefore developed an HLE ce...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1998.0551
更新日期：1998-11-01 00:00:00
abstract：:Hypoxia inducible factor (HIF) regulates expression of over 60 genes by binding to hypoxia response elements (HRE) located upstream of the transcriptional start sites. Many genes encoding proteins involved in iron transport and homeostasis are regulated by HIF. Expression of iron handling proteins can also be translat...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.05.010
更新日期：2014-08-01 00:00:00
abstract：:To assess the ability of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to detect blood retinal barrier (BRB) damage in patients with diabetic macular edema (DME). DCE-MRI with 0.1 mmol Gd-DTPA was used to measure BRB permeability in 10 healthy and visually normal subjects and eight patients with DME, ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2005.01.015
更新日期：2005-07-01 00:00:00
abstract：:Lens development and transparency have been hypothesized to depend on intercellular gap junction channels, consisting of alpha3 (Cx46) and alpha8 (Cx50) connexin subunits, to transport metabolites, secondary messages and ions between lens cells. To evaluate this hypothesis, we have generated alpha3(-/-) alpha8(-/-) do...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.03.013
更新日期：2006-09-01 00:00:00
abstract：:Careful control of iron availability in the retina is central to maintenance of iron homeostasis, as its imbalance is associated with oxidative stress and the progression of several retinopathies. Ferritin, known for its role in iron storage and detoxification, has also been proposed as an iron-transporter protein, th...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2020.108292
更新日期：2021-01-01 00:00:00
abstract：:A technology has recently been developed that allows for the rapid transduction of full-length functionally active proteins into intact tissue through intravenous injection and into cultured cells. This technology involves the fusion of an 11 amino acid sequence of the HIV TAT protein to the protein of interest. In th...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2003.12.010
更新日期：2004-05-01 00:00:00
abstract：:The purpose of this investigation is to characterize parvalbumin-immunoreactive (IR) neurons in the inner nuclear layer (INL) of zebrafish retina through immunocytochemistry, quantitative analysis, and confocal microscopy. In the INL, parvalbumin-IR neurons were located in the inner marginal portion of the INL. On the...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2008.11.014
更新日期：2009-03-01 00:00:00
abstract：:To determine the effect of roscovitine, a potent antiviral in tissue culture administered intramuscularly to rabbits or by eye drops to mice for the treatment of herpetic keratitis this study was commenced.New Zealand white rabbits infected with McKrae strain herpesvirus (HSV-1) were treated twice a day with 10mg Rosc...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(03)00056-3
更新日期：2003-06-01 00:00:00
abstract：:Retinal vein occlusion (RVO) is an intractable eye disease that results in reduced visual acuity, associated with retinal ischemia, hemorrhage, and edema. RVO results in excessive ROS production in the retina, causing inflammation and retinal edema. A free radical scavenger, 4-(4-acetylpiperazin-1-yl)-2-(1H-imidazole-...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2021.108453
更新日期：2021-01-24 00:00:00
abstract：:Corneal autofluorescence, as measured with a commercial scanning fluorophotometer (lambda(exc): 415-491 nm; lambda(em): 515-630 nm), is increased in patients with diabetes mellitus. However, such fluorophotometers register an average fluorescence signal over all corneal layers as a consequence of their limited axial r...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1999.0733
更新日期：1999-11-01 00:00:00
abstract：:The polarity of retinal pigmented epithelia (RPE) from chicken embryos was studied in primary cell culture. Since cultured RPE approximates the morphological polarity of RPE in vivo, we investigated whether this polarity extends to the distribution of plasma membrane proteins that are peculiar to RPE. In contrast to o...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(90)90156-o
更新日期：1990-10-01 00:00:00
abstract：:The conjunctival associated lymphoid tissue is considered to be an integral part of the mucosal immune system. Under normal circumstances immune mechanisms in mucosal associated lymphoid tissue of the gut and bronchus can selectively suppress, rather than enhance, immune responsiveness to encountered antigens, inducin...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1997.0297
更新日期：1997-06-01 00:00:00
abstract：:Human trabecular-meshwork (HTM) cells in culture convert arachidonic acid to two products: PGE2 and 6-keto PGF1 alpha. Prostaglandin PGE2 was the major product of arachidonic-acid metabolism. The synthesis and release of PGE2 and 6-keto PGF1 alpha was inhibited by a 15-min pre-treatment with indomethacin (5 X 10(-6) M...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(86)90085-0
更新日期：1986-12-01 00:00:00
abstract：:The effect of angiotensin II was studied in vitro on ring segments of bovine retinal resistance arteries (i.d. 126-271 microns) and posterior ciliary arteries (i.d. 207-1153 microns). Although the retinal resistance arteries were responsive to 5-hydroxytryptamine, prostaglandin F2 alpha, and changes in extracellular K...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(90)90034-r
更新日期：1990-05-01 00:00:00
abstract：:The in vitro and in vivo effects of a new immunomodulating agent, bucillamine, on experimental autoimmune uveitis (EAU) was studied in the rat. The capacity of S-antigen-sensitized lymphocytes to proliferate in response to the antigen or to produce antigen-specific antibodies was significantly suppressed by bucillamin...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1994.1036
更新日期：1994-04-01 00:00:00
abstract：:Fiber cells of the ocular lens are arranged in a series of concentric shells. New growth shells are added continuously to the lens surface and, as a consequence, the preexisting shells are buried. To focus light, the refractive index of the lens cytoplasm must exceed that of the surrounding aqueous and vitreous humors...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
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更新日期：2017-03-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(84)90075-7
更新日期：1984-12-01 00:00:00
abstract：:AII amacrine cells are critical interneurons in the rod pathway of mammalian retina, active primarily in dim lighting conditions. Melatonin, a neuromodulator produced at night in the retina, is believed to induce retinal adaptation to dim lighting conditions in most vertebrate species examined to date, including human...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(03)00123-4
更新日期：2003-09-01 00:00:00
abstract：:Patients with inflammatory bowel disease suffer not only from gut inflammation, but also from extraintestinal manifestations of the disease, including ocular pathology. The mechanisms causing ocular inflammation in these patients are unknown. The purpose of the current study was to investigate the possible vascular ch...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2013.06.023
更新日期：2013-10-01 00:00:00
abstract：:This review offers a contemporary history of the renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems with emphasis on how these complex systems affect the eye. It describes the types of communication (cross-talk) between the two systems and evaluates their potential role in the development of diabetic retinopat...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2017.05.007
更新日期：2018-01-01 00:00:00
abstract：:Recent studies of the distribution and relative concentration of caveolin-1 in fractions of bovine lens epithelial and fiber cells have led to the novel concept that caveolin-1 may largely exist as a peripheral membrane protein in some cells. Caveolin-1 is typically viewed as a scaffolding protein for caveolae in plas...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2007.05.011
更新日期：2007-10-01 00:00:00
abstract：:Previous studies have suggested that a mannose receptor mediates the phagocytic uptake of effete rod outer segments by retinal pigment epithelial cells. In the present study, the effect of adding a soluble ligand for the mannose receptor, horseradish peroxidase, was examined. Cultured retinal pigment epithelial cells ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(05)80144-7
更新日期：1995-10-01 00:00:00
abstract：:Cataract is a multifactorial disease, and a large variety of stressors induce cataracts. Many cataractogenic stressors and endoplasmic reticulum (ER) stressors induce the unfolded protein response (UPR) in various cell types. The UPR is known to produce reactive oxygen species (ROS) prior to the inducement of apoptosi...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.01.033
更新日期：2006-09-01 00:00:00
abstract：:Several scleral cross-linking (SXL) methods were suggested to increase the biomechanical stiffness of scleral tissue and therefore, to inhibit axial eye elongation in progressive myopia. In addition to scleral cross-linking and biomechanical effects caused by riboflavin and light irradiation such a treatment might ind...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2015.07.005
更新日期：2015-10-01 00:00:00
abstract：:The combined effects of adenosine and acetylcholine on the intracellular free-Ca2+ concentration in nonpigmented epithelial cells of the rabbit ciliary body were investigated using fura-2 fluorescence-ratio imaging. Acetylcholine (10 microM) by itself produced a modest increase in [Ca2+]i. Acetylcholine in combination...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1996.0194
更新日期：1997-02-01 00:00:00
abstract：:We have previously shown that corticotropin-releasing hormone plays an important proinflammatory role in the induction of experimental autoimmune uveoretinitis. In this study, we examined the role of apoptosis in the destruction of the retina during experimental autoimmune uveoretinitis, and the role of corticotropin-...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2001.0992
更新日期：2001-06-01 00:00:00
