June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Serine/Arginine-Rich Protein Kinase Blockade Attenuates Choroidal Neovascularization
Author Affiliations & Notes
  • Zhenyu Dong
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Kousuke Noda
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Atsuhiro Kanda
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Junichi Fukuhara
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Ryo Ando
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Miyuki Murata
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Wataru Saito
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Masatoshi Hagiwara
    Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • Susumu Ishida
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Footnotes
    Commercial Relationships Zhenyu Dong, None; Kousuke Noda, None; Atsuhiro Kanda, None; Junichi Fukuhara, None; Ryo Ando, None; Miyuki Murata, None; Wataru Saito, None; Masatoshi Hagiwara, Kinopharma Co Ltd (I), Kinopharma Co Ltd (P); Susumu Ishida, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4605. doi:
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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)

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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 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.

Results: 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.

Conclusions: 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.

Keywords: 453 choroid: neovascularization  
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