title: Therapeutic potential of semaphorin 3E for the treatment of choroidal neovascularization.
abstract: OBJECTIVE
  We investigated the effects of semaphorin 3E (Sema3E)/PlexinD1 signaling in the development of choroidal neovascularization (CNV) and explored the therapeutic potential of the pathway.
  
  
  METHODS
  We used a laser-induced CNV model in the mouse. The expression of Sema3E and PlexinD1 was evaluated with immunohistochemistry, real-time RT-PCR, and Western blotting. After the intravitreal injection of Sema3E, the CNV size was measured on immunostained flat mounts. The CNV size was compared between inducible PlexinD1 homozygous mice and heterozygous knockout mice.
  
  
  RESULTS
  The presence of PlexinD1 was confirmed immunohistochemically in the endothelial cells of CNV. The expression of PlexinD1 mRNA was elevated after laser photocoagulation with its peak expression at day 5 (1.72 times, compared to baseline; P < 0.01). The intravitreal injection of recombinant Sema3E decreased the CNV size (16,320.9 ± 8316.0 μm(2) in the control eyes versus 9487.4 ± 4424.1 μm(2) in the eyes administered 0.1-μg Sema3E, P < 0.01). This inhibitory effect of Sema3E in the formation of CNV was canceled in the inducible PlexinD1 knockout mice (24,920.8 ± 24,684.8 μm(2) in homozygous knockout mice and 13,152.6 ± 7973.0 μm(2) in heterozygous knockout mice, P = 0.014).
  
  
  CONCLUSIONS
  These results indicate that Sema3E-PlexinD1 signaling is involved in the development of CNV. Stimulation of the pathway has therapeutic potential for CNV. Further studies are needed to evaluate the effects for clinical applications.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suda
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Congrong
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Oishi
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Retinal Vascular Biology, Nagoya City University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Uemura
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis / Q000235:genetics*; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006023:Glycoproteins / Q000008:administration & dosage*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D058449:Intravitreal Injections; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D039961:Semaphorins
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C473552:Plxnd1 protein, mouse; D012333:RNA, Messenger; C111150:Sema3e protein, mouse; D039961:Semaphorins
keywords: choroidal neovascularization; plexin; semaphorin