Abstract：
:Neovascular age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Although intravitreal injection of anti-VEGF antibodies and VEGF Trap have significant clinical benefits, the complications of intravitreal injection, drug resistance and patient compliance still need to be concerned. In this study, the effects of an orally administered multi-targeted tyrosine kinase inhibitor (Lenvatinib, E7080) were evaluated in vitro and in vivo on neovascular AMD mouse model. The results showed that E7080 effectively inhibited the proliferation, migration and tubule formation of human choroidal microvascular endothelial cells (HCMECs), and suppressed the angiogenesis of zebrafish subintestinal vessels without causing malformation. The anti-angiogenic effect of E7080 on the laser-induced choroidal neovascularization (CNV) mouse model by oral administration of 10 mg/kg/day was observed. The fluorescein angiography showed CNV leakage area in treatment group vs control group was 3.407 ± 0.2939 vs 5.202 ± 0.9001 (P = .0133) at day 7th post laser-induced CNV, 1.138 ± 0.4334 vs 3.122 ± 0.3466 (P = .0064) at day 14th, 1.401 ± 0.6577 vs 2.781 ± 0.9815 (P = .00262) at day 21th respectively. Moreover, pharmacokinetics analysis in rat retina showed that E7080 rapidly penetrated the blood-retina barrier to retina through oral administration. The T1/2 in retina was 3.81 ± 0.77 h, the Tmax was 4.60 ± 0.73 h, the AUC0-∞ was 110448.51 ± 18532.51 h*ng/g after a single dose administration analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). In conclusion, our study suggested that orally administered E7080 can be a novel therapeutic strategy for neovascular AMD.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Wei X,Zhang T,Yao Y,Zeng S,Li M,Xiang H,Zhao C,Cao G,Li M,Wan R,Yang P,Yang Jdoi
10.1016/j.exer.2017.12.009subject
Has Abstractpub_date
2018-03-01 00:00:00pages
2-11eissn
0014-4835issn
1096-0007pii
S0014-4835(17)30681-4journal_volume
168pub_type
杂志文章abstract：:The purpose of this study was to correlate potential mechanisms with site(s) of action for TNPA-induced ocular hypotension. In response to R(-)-2, 10, 11-trihydroxy-N-propyl-noraporphine hydrobromide (TNPA, 75 microg), a D2 dopamine receptor agonist, the intraocular pressure decreased by 4.5 and 8 mm Hg at 1 and 2 hr,...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1999.0734
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abstract：:The development of a synthetic material allowing increased cellular adhesion and ingrowth would improve keratoprosthetic devices and requires an understanding of cell colonization processes. Interlamellar implantation of hydrophobic synthetic material may lead to poor corneal nutrition with subsequent necrosis. The pr...
journal_title：Experimental eye research
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doi：10.1006/exer.1994.1193
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abstract：:Misregulation of the innate immune response and other immune-related processes have been suggested to play a critical role in the pathogenesis of a number of different neurodegenerative diseases, including age related macular degeneration. In an animal model for photoreceptor degeneration, several genes of the innate ...
journal_title：Experimental eye research
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doi：10.1016/j.exer.2006.08.017
更新日期：2007-01-01 00:00:00
abstract：:The effects of metabolic inhibitors on the apical and basal membrane potentials were studied in the isolated retinal pigment epithelium of the lizard Gekko gekko. Adding dinitrophenol or cyanide or cooling the tissue to 15 degrees C first depolarized the apical membrane and then hyperpolarized the basal membrane. The ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(90)90015-m
更新日期：1990-01-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2007.08.001
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abstract：:Endostatin is an endogenous angiogenesis inhibitor which requires E-selectin for its antiangiogenic activity. The aim of this study was to investigate the expression of endostatin in human choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD) with regard to vascularization and proli...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2005.12.017
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abstract：:With the combined purpose of facilitating useful vision over a lifetime, a number of ocular cells have evolved specialized features not found elsewhere in the body. The trabecular meshwork (TM) cell at the irido-corneal angle, which is a key regulator of intraocular pressure, is no exception. Examination of cells in c...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2016.07.009
更新日期：2017-05-01 00:00:00
abstract：:We have determined the pattern of RNA labeling (uridine incorporation) in the normal retina of the domestic cat. One eye in each of eight cats was labeled by injecting [3H]uridine into the vitreous cavity. Two of the labeled eyes had the lens and vitreous removed 10 days before labeling. Three additional animals recei...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(90)90066-4
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abstract：:Autophagy is a lysosomal degradative process that is essential for cellular homeostasis and metabolic stress adaptation. Defective autophagy is involved in the pathogenesis of many diseases including granular corneal dystrophy type 2 (GCD2). GCD2 is an autosomal dominant disorder caused by substitution of histidine fo...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
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更新日期：2016-03-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(84)90099-x
更新日期：1984-02-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.02.012
更新日期：2006-09-01 00:00:00
abstract：:Recent evidence suggests that mucosal epithelial cells are capable of actively participating in immune reactions via expression of surface antigens, such as adhesion molecules, and synthesis of cytokines. This appears to be important in the pathophysiology of non-ocular allergic disorders. The objectives of the experi...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1998.0528
更新日期：1998-11-01 00:00:00
abstract：:An attachment to (Haag-Streit and Topcon) slit-lamps is described. This permits projection of a patterned target into the eye and the visual or photographic analysis of the details of the image reflected from the posterior surface of the crystalline lens. A numerical assessment can then be made of the optical quality ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(92)90124-b
更新日期：1992-09-01 00:00:00
abstract：:Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2016.08.008
更新日期：2016-10-01 00:00:00
abstract：:Recently we determined that the Transient Receptor Potential Vanilloid 4 ion channel (TRPV4) has a crucial signaling role in a pathway that regulates various aspects of lens epithelium function. Here, we report on a different TRPV channel, TRPV1, in porcine lens. The presence of TRPV1 in the lens was evident from RT-P...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2018.04.006
更新日期：2018-07-01 00:00:00
abstract：:The present study determined whether topical latanoprost, a prostaglandin (PG) F(2alpha) analog, influences the induction of anterior chamber-associated immune deviation (ACAID), corneal neovascularization (NV) or survival of corneal allografts in mice. BALB/c mice received topical latanoprost or PGE(2) once or multip...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2007.11.012
更新日期：2008-02-01 00:00:00
abstract：:By means of X-ray diffraction analysis, structural conversions of crystallins in human lens were detected in senile cataract and upon artificial dehydration of lens tissue. In senile cataract certain characteristics of the native three-dimensional structure of gamma- and beta-crystallins are completely lost, whereas d...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(89)80044-2
更新日期：1989-11-01 00:00:00
abstract：:Many ocular surface tests have been developed for the clinical diagnosis of keratoconjunctivitis sicca, and several have been used to 'validate' animal models of Sjogren's and non-Sjogren's dry eye. However, many of these tests themselves have not been systematically studied or standardized, and yet their use in anima...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2004.07.002
更新日期：2004-11-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章,meta分析,评审
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更新日期：2015-10-01 00:00:00
abstract：:A shift or displacement of the retinal blood vessels (RBVs) with neuroretinal rim thinning indicates the progression of glaucomatous optic neuropathy. In chronic open angle glaucoma, individuals with RBV positional shifts exhibit more rapid visual field loss than those without RBV shifts. The retinal vessels reportedl...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2017.07.012
更新日期：2017-09-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.11.008
更新日期：2015-01-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.09.019
更新日期：2007-02-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2016.12.007
更新日期：2017-02-01 00:00:00
abstract：:The differentiation of rat lens epithelial cells to fibre cells can be mimicked using lens epithelial explants, which differentiate in vitro when exposed to fibroblast growth factor (FGF). A previous study demonstrated that FGF is required only for initiation of differentiation: once induced by FGF, differentiation ca...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1998.0534
更新日期：1998-10-01 00:00:00
abstract：:Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were isolated from frog retinal rod outer segment (ROS) membranes and their major molecular species determined. Saturated fatty acids are predominantly located on position-1 and polyunsaturates on position-2, although this assignment is not absolute. One-fifth...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(83)90075-1
更新日期：1983-08-01 00:00:00
abstract：:Choroidal neovascularization (CNV) is one of the severe pathological consequences of the end-stage of age-related macular degeneration (AMD). Several lines of evidence implicate increased levels of vascular endothelial growth factor (VEGF) in the retinas of AMD patients. Current available agents for the inhibition of ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2010.06.019
更新日期：2010-09-01 00:00:00
abstract：:Excised bovine and rhesus monkey vitreous samples were subjected to different hydrostatic pressures (0.03, 1 and 2 atm) for 12 hr. At the end of the experiment the samples were frozen in a -70 degrees C dry ice-acetone bath and thereafter maintained in frozen conditions. Differential scanning calorimetry (DSC) was use...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2001.1021
更新日期：2001-07-01 00:00:00
abstract：:Recoverin is a calcium-binding protein identified as an autoantigen in a paraneoplastic degenerative disease of the human retina known as cancer-associated retinopathy (CAR). In this study we investigated whether recoverin could elicit an immune response leading to the degeneration of photoreceptor cells in a rodent r...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1994.1130
更新日期：1994-10-01 00:00:00
abstract：:Iris pigment epithelial (IPE) cells from the anterior segment in the eye are able to suppress activation of bystander responder T cells in vitro. The cultured IPE cells fully suppress proliferation and cytokine production by responder T cells via direct cell-to-cell contact. We have now investigated whether primary cu...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2009.01.011
更新日期：2009-06-01 00:00:00
abstract：:Post-translational modifications and/or structural changes induced by modifications are likely causes of the decrease in crystallin solubility associated with aging and the development of cataract. Characterization of human lens crystallins by mass spectrometry has demonstrated that betaB2-crystallin undergoes less mo...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2001.1023
更新日期：2001-08-01 00:00:00
