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PMID: 23152758 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The semaphorin 3A inhibitor SM-345431 accelerates peripheral nerve regeneration and sensitivity in a murine corneal transplantation model.

PloS one ·Vol. 7 ·No. 11 ·2012-00-00 ·Pages e47716

Omoto M, Yoshida S, Miyashita H, Kawakita T, Yoshida K, Kishino A, Kimura T, Shibata S, Tsubota K, Okano H, Shimmura S

Abstract

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. 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. 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.

MeSH Terms
Animals Cell Proliferation/drug effects Cell Survival/drug effects Cornea/innervation,pathology,surgery Corneal Neovascularization Corneal Transplantation Epithelial Cells/drug effects Mice Mice, Transgenic Models, Animal Neovascularization, Physiologic/drug effects Nerve Regeneration/drug effects Peripheral Nerves/drug effects,physiology Semaphorin-3A/antagonists & inhibitors,metabolism Xanthones/pharmacology
Chemicals
Semaphorin-3A Xanthones vinaxanthone
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Omoto Masahiro
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Yoshida Satoru
Miyashita Hideyuki
Kawakita Tetsuya
Yoshida Kenji
Kishino Akiyoshi
Kimura Toru
Shibata Shinsuke
Tsubota Kazuo
Okano Hideyuki
Shimmura Shigeto
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0047716
Published
2012-00-00
Epub
2012-00-09
Pages
e47716
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3494696
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0047716 PMC Full Text View journal details
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