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Zhenyu Dong, Kousuke Noda, Atsuhiro Kanda, Junichi Fukuhara, Ryo Ando, Miyuki Murata, Wataru Saito, Masatoshi Hagiwara, Susumu Ishida; Serine/Arginine-Rich Protein Kinase Blockade Attenuates Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4605.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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 by enzyme-linked immunosorbent assay. Expression levels of total Vegf and exon 8a-containing Vegf isoforms were assessed using real-time PCR, and F4/80 (a specific marker for macrophage) using real-time PCR and immunostaining.
SRPIN340 inhibited CNV formation in a dose-dependent manner. Compared with the vehicle, SRPIN340 significantly decreased the protein levels of VEGF, MCP-1 and ICAM-1, and consequently inhibited macrophage infiltration. Furthermore, SRPIN340 suppressed the gene expression levels of both total Vegf and exon 8a-containing Vegf isoforms.
SRPIN340, a specific inhibition of SRPK, suppressed Vegf expression and attenuates CNV formation. Our data suggest the possibility that SRPIN340 is applicable for neovascular age-related macular degeneration as a novel chemical therapeutics.
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