The Effect of CM082, an Oral Tyrosine Kinase Inhibitor, on Experimental Choroidal Neovascularization in Rats.
The Effect of CM082, an Oral Tyrosine Kinase Inhibitor, on Experimental Choroidal Neovascularization in Rats.
复制标题
口服酪氨酸激酶抑制剂CM082对大鼠实验性脉络膜新生血管的影响
DOI：
10.1155/2017/6145651
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发表时间：
2017
影响因子：
1.9
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Ren C;Shi H;Jiang J;Liu Q;Du Y;He M;Cai W;Wei Q;Yu J
本研究的目的是评估CM 082对激光诱导的脉络膜新生血管（CNV）大鼠模型中CNV发展的影响，并确定眼组织中的药物浓度。在大鼠中建立激光诱导的CNV模型后，经口给予CM 082。使用眼底荧光素血管造影术（FFA）、CNV组织学和视网膜色素上皮（RPE）脉络膜-巩膜眼杯分析来评估CM 082对CNV病变的影响。采用液相色谱-串联质谱法（LC-MS/MS）测定血浆和眼组织中CM 082的浓度。FFA、组织学和RPE-脉络膜-巩膜眼杯分析的结果表明，CM 082治疗（10 mg/kg/d或30 mg/kg/d）的大鼠表现出比对照组显著更少的新血管形成。眼内CM 082的总浓度（172.86 ± 57.11 ng/g）与血浆浓度（196.87 ± 73.13 ng/ml）相似。在眼内，CM 082及其代谢物的浓度在视网膜-巩膜中最高。因此，口服给药的CM 082有效地穿过血-视网膜屏障（BRB）到达Brown Norway大鼠的视网膜。因此，在10 mg/kg/d和30 mg/kg/d剂量下，CM 082能够减少激光诱导的CNV大鼠模型中的CNV病变。
The aims of this study were to evaluate the effects of CM082 on the development of choroidal neovascularization (CNV) in a laser-induced CNV rat model and to determine the drug concentration in the ocular tissues. After the laser-induced CNV model was established in rats, CM082 was orally administered. The effects of CM082 on the CNV lesions were assessed using fundus fluorescein angiography (FFA), CNV histology, and retinal pigment epithelium- (RPE-) choroid-sclera eyecup analysis. The concentrations of CM082 in the plasma and eye tissues were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results of FFA, histology, and RPE-choroid-sclera eyecup analysis demonstrated that the CM082-treated (10 mg/kg/d or 30 mg/kg/d) rats exhibited significantly less neovascularization than did the control group. The total concentration of CM082 in the eyes (172.86 ± 57.11 ng/g) was similar to that in the plasma (196.87 ± 73.13 ng/ml). Within the eye, the concentrations of CM082 and its metabolites were highest in the retina-sclera. The orally administered CM082 thus effectively passed through the blood-retina barrier (BRB) to reach the retina in the Brown Norway rats. Therefore, at both 10 mg/kg/d and 30 mg/kg/d, CM082 was able to reduce CNV lesions in the laser-induced CNV rat model.
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影响因子：
17.1
作者：
Sidman RL;Li J;Lawrence M;Hu W;Musso GF;Giordano RJ;Cardó-Vila M;Pasqualini R;Arap W
通讯作者：
Arap W
影响因子：
3.9
作者：
Silvestri, G.;Williams, M. A.;Muldrew, K. A.
通讯作者：
Muldrew, K. A.
影响因子：
158.5
作者：
Rosenfeld, Philip J.;Brown, David M.;Kim, Robert Y.
通讯作者：
Kim, Robert Y.
DOI：
10.1007/978-3-540-78281-0_7
发表时间：
2010-01-01
期刊：
ANGIOGENESIS INHIBITION
影响因子：
--
作者：
Hellberg, Carina;Ostman, Arne;Heldin, C. -H.
通讯作者：
Heldin, C. -H.
影响因子：
--
作者：
AIELLO, LP;NORTHRUP, JM;IWAMOTO, MA
通讯作者：
IWAMOTO, MA