title: Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Dong
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kanda
authors.forename: Junichi
authors.initials: J
authors.lastname: Fukuhara
authors.forename: Ryo
authors.initials: R
authors.lastname: Ando
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murata
authors.forename: Wataru
authors.initials: W
authors.lastname: Saito
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hagiwara
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D017346:Protein Serine-Threonine Kinases
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