Effect of a Sema3A inhibitor treatment in a murine dry eye model

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Fujita Health University (2018); National Institutes of Biomedical Innovation, Health and Nutrition (2017); Keio University (2016)
• Principal Investigator: Satoru Yoshida 藤田医科大学, 医学部, 講師 (50398781)
• Co-Investigator(Kenkyū-buntansha): 榛村 重人 慶應義塾大学, 医学部(信濃町), 准教授 (00235780)
• Research Collaborator: TSUBOTA kazuo (40163878) ; OKANO hideyuki (60160694) ; YAMAZOE katsuya ; YAMAZAKI risa ; SHIMIZU shota ; YASUDA miyuki (80574912)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 角膜神経再生 / Semaphorin3A / ドライアイ

Outline of Final Research Achievements

Semaphorin 3A (Sema3A) is expressed in corneal epithelium and is known to act as a repellent for axonal growth of neurons. In dry eye disease (DED), corneal nerves, which responsible for corneal sensations and tear secretion, are compromised. Therefore, inhibition of Sema3A may protect corneal nerve dysfunction in DED. Using a murine dry eye model, which developed by removing an extra-orbital lacrimal gland, we found that topical application of a selective Sema3A inhibitor, vinaxanthone, prevent disruption of corneal nerves, preserve corneal sensitivity and tear volume. Furthermore, formation of corneal epithelial erosion was suppressed in DED model mice treated with the inhibitor. These results suggest that topical application of the selective Sema3A inhibitor may be effective for treatment of DED.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

ドライアイは有病率が高い疾患であるが、神経再生または保護の観点からの治療法はなく、現行の涙液構成成分の補充療法だけでは治療が不十分な例も多い。神経再生を促進するビナキサントンを新たなドライアイ治療薬として開発できれば、より多くのドライアイ患者の症状を軽減できると考えられ、本研究でその可能性を示すことができた。ビナキサントンを用いることで、レーザー屈折矯正手術（レーシック）や全層角膜移植術の後に生じることのある知覚低下や涙液分泌低下の症状を緩和できる可能性もある。