Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization
Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization
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发表时间：
2013-03
期刊：
影响因子：
2.2
通讯作者：
Zhenyu Dong;K. Noda;Atsuhiro Kanda;Junichi Fukuhara;Ryo Ando;M. Murata;W. Saito;M. Hagiwara;S. Ishida
中科院分区：
文献类型：
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作者：
Zhenyu Dong;K. Noda;Atsuhiro Kanda;Junichi Fukuhara;Ryo Ando;M. Murata;W. Saito;M. Hagiwara;S. Ishida
目的研究富丝氨酸/精氨酸蛋白激酶（SRPK）特异性抑制剂SRPIN340对小鼠脉络膜新生血管（CNV）形成的抑制作用。方法采用激光光凝法诱导C57BL/6J小鼠CNV，玻璃体内注射SRPIN340或对照物。治疗后7天，使用平载技术评估CNV大小。采用酶联免疫吸附法检测视网膜色素上皮-脉络膜复合体中血管内皮生长因子（VEGF）和炎症相关分子(单核细胞趋化蛋白（MCP)-1和细胞间粘附分子(ICAM)-1）的蛋白水平。利用实时PCR技术评估总Vegf、含有Vegf的外显子8a亚型和F4/80（巨噬细胞特异性标志物）的表达水平。结果SRPIN340抑制CNV形成呈剂量依赖性。与对照物相比，SRPIN340显著降低VEGF、MCP-1、ICAM-1蛋白水平，从而抑制巨噬细胞浸润。此外，SRPIN340抑制了总Vegf和含有8a外显子的Vegf亚型的基因表达水平。结论SRPIN340是SRPK的特异性抑制剂，可抑制Vegf的表达，减轻CNV的形成。我们的数据表明，SRPIN340可能作为一种新的化学疗法适用于新生血管性年龄相关性黄斑变性。
Purpose To investigate the applicability of serine/arginine-rich protein kinase (SRPK)-specific inhibitor, SRPIN340, for attenuation of choroidal neovascularization (CNV) formation using a mouse model. Methods Laser photocoagulation was performed to induce CNV in C57BL/6J mice, followed by intravitreal injection of SRPIN340 or vehicle. Seven days after the treatment, the CNV size was evaluated using a flatmount technique. Protein levels of vascular endothelial growth factor (VEGF) and inflammation-associated molecules, such as monocyte chemoattractant protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1, in the retinal pigment epithelium-choroid complex were measured with enzyme-linked immunosorbent assay. Expression levels of total Vegf, exon 8a-containing Vegf isoforms, and F4/80 (a specific marker for macrophage) were assessed using real-time PCR. Results SRPIN340 inhibited CNV formation in a dose-dependent manner. Compared with the vehicle, SRPIN340 significantly decreased the protein levels of VEGF, MCP-1, ICAM-1, and consequently inhibited macrophage infiltration. Furthermore, SRPIN340 suppressed the gene expression levels of total Vegf and exon 8a-containing Vegf isoforms. Conclusions SRPIN340, a specific inhibitor of SRPK, suppressed Vegf expression and attenuated CNV formation. Our data suggest the possibility that SRPIN340 is applicable for neovascular age-related macular degeneration as a novel chemical therapeutics.