title: The semaphorin 3A inhibitor SM-345431 accelerates peripheral nerve regeneration and sensitivity in a murine corneal transplantation model.
abstract: BACKGROUND
  Peripheral nerve damage of the cornea is a complication following surgery or infection which may lead to decreased visual function. We examined the efficacy of the semaphorin 3A inhibitor, SM-345431, in promoting regeneration of peripheral nerves in a mouse corneal transplantation model.
  
  
  RESULTS
  P0-Cre/Floxed-EGFP mice which express EGFP in peripheral nerves cells were used as recipients of corneal transplantation with syngeneic wild-type mouse cornea donors. SM-345431 was administered subconjunctivally every 2 days while control mice received vehicle only. Mice were followed for 3 weeks and the length of regenerating nerves was measured by EGFP fluorescence and immunohistochemistry against βIII tubulin. Cornea sensitivity was also measured by the Cochet-Bonnet esthesiometer. CD31 staining was used to determine corneal neovascularization as a possible side effect of SM-345431. Regeneration of βIII tubulin positive peripheral nerves was significantly higher in SM-345431 treated mice compared to control. Furthermore, corneal sensitivity significantly improved in the SM-345431 group by 3 weeks after transplantation. Neovascularization was limited to the peripheral cornea with no difference between SM-345431 group and control.
  
  
  CONCLUSIONS
  Subconjunctival injections of SM-345431 promoted a robust network of regenerating nerves as well as functional recovery of corneal sensation in a mouse keratoplasty model, suggesting a novel therapeutic strategy for treating neurotrophic corneal disease.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Omoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Yoshida
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Miyashita
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawakita
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kishino
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Shigeto
authors.initials: S
authors.lastname: Shimmura
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003315:Cornea / Q000294:innervation / Q000473:pathology / Q000601:surgery; D016510:Corneal Neovascularization; D016039:Corneal Transplantation; D004847:Epithelial Cells / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000502:physiology*; D040121:Semaphorin-3A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D040121:Semaphorin-3A; D044004:Xanthones; C086647:vinaxanthone