Elucidation of the Mechanisms of Corneal Epithelial Wound Healing and Inflammation by Semaphorin 3a

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09753
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Keio University
• Principal Investigator: Hatou Shin 慶應義塾大学, 医学部, 特任講師 (70327542)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Semaphorin3A / 樹状細胞 / 角膜神経 / 角膜上皮 / ドライアイ / 抗炎症作用 / 涙腺神経切断

Outline of Final Research Achievements

Semaphorin 3A (Sema3A) is one of the molecules that regulate nerve terminal growth and inflammation. To elucidate the role of Sema3A in corneal wound healing from the perspectives of neuroprotection and inflammation, a mouse model with lacrimal gland nerve transection was created. Three groups were compared: a PBS eye drop group, a Sema3A inhibitor eye drop group, and a sham group. The results showed that the Sema3A inhibitor promoted the recovery of tear production, suppressed corneal epithelial damage, and reduced both the number and activation of dendritic cells in the central cornea. Additionally, there was a tendency to prevent atrophy and fibrosis of the lacrimal gland.
It is hypothesized that the direct effect of the Sema3A inhibitor on dendritic cells resulted in anti-inflammatory effects, leading to the protection of the corneal epithelium and the recovery of tear production.

Free Research Field

角膜細胞生物学

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、現行の涙液成分の補充療法や、ステロイドによる抗炎症療法だけでは治療が不十分な例も多い。
神経末端の成長や炎症を制御するSema3A阻害剤の研究は、角膜の神経損傷や炎症の分子メカニズムを解明し、ドライアイの根本的な原因に直接作用する新たな治療法を提供できる可能性がある。本研究では、Sema3A阻害剤による涙液量の回復や角膜上皮障害の抑制、樹状細胞を介した眼表面炎症の抑制効果の機序を見出すことができた。Sema3A阻害剤が、ステロイドの副作用となる眼圧上昇、易感染性等を伴わない抗炎症剤として実用化できれば、臨床的意義が高い治療選択肢の１つになる可能性がある。