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Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization.
|Title: ||Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization.|
|Authors: ||Dong, Zhenyu Browse this author|
|Noda, Kousuke Browse this author →KAKEN DB|
|Kanda, Atsuhiro Browse this author →KAKEN DB|
|Fukuhara, Junichi Browse this author|
|Ando, Ryo Browse this author|
|Murata, Miyuki Browse this author|
|Saito, Wataru Browse this author|
|Hagiwara, Masatoshi Browse this author|
|Ishida, Susumu Browse this author →KAKEN DB|
|Issue Date: ||5-Mar-2013|
|Publisher: ||Molecular Vision|
|Journal Title: ||Molecular vision|
|Start Page: ||536|
|End Page: ||543|
|Abstract: ||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.|
|Appears in Collections:||医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)|
Submitter: 石田 晋