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Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization.

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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
Volume: 19
Start Page: 536
End Page: 543
PMID: 23559848
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.
Type: article
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

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