Treatment strategy for neuroparalytic keratopathy with a view to trigeminal nerve regeneration.

• Project/Area Number: 18K16963
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: TANAKA SAIICHI 和歌山県立医科大学, 医学部, 准教授 (60316106)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 角膜 / 三叉神経 / 創傷治癒 / ソニックヘッジホッグ / ソニック・ヘッジホッグ / 神経麻痺性角膜症

Outline of Final Research Achievements

Circular corneal epithelial defects were created in mice, and wound healing and cell proliferation were examined. There was no statistically significant difference in the residual area of the corneal epithelial defect between ShhΔCE and Shhf/wt mice, and the number of BrdU-positive cells was significantly suppressed in the corneal epithelium of ShhΔCE mice 6 hours after corneal epithelial detachment compared to that of Shhf/wt mice. Immunostaining for Sox9 expression during corneal epithelial wound healing revealed enhanced expression of Sox9 in the migrating corneal epithelium of ShhΔCE mice at 12 hours after corneal epithelial detachment compared to Shhf/wt mice. Whole-mount immunostaining of the cornea with TUJ1 antibody showed suppression of corneal nerve distribution and hypersensitivity.

Academic Significance and Societal Importance of the Research Achievements

神経麻痺性角膜症は視力障害や疼痛に関与する。ただ　その原因に関してはいまだ不明なために、動物実験モデルにてその機序を解明することで視力障害や疼痛の軽減につながる。今回の研究では角膜の創傷治癒や角膜神経の分布に関してソニックヘッジホッグ（Shh）が関与していることが示唆された。創傷治癒にはいろいろな作用機序が存在するが、その一つの関与がわかったことで、今後の創傷治癒においての臨床的な治療薬の解明につながると考える

Research Products

• [Journal Article] Inhibition of Rho kinase suppresses capsular contraction following lens injury in mice (2020)
  • Author(s): Tanaka Sai-Ichi、Ichikawa Kana、Miyajima Masayasu、Okada Yuka、Saika Shizuya
  • Journal Title: Taiwan Journal of Ophthalmology Volume: 10 Issue: 2 Pages: 100-105
  • DOI: 10.4103/tjo.tjo_80_19
  • Peer Reviewed / Open Access
• [Presentation] 内因性ソニックヘッジホッグ(Shh)は角膜内の神経分布に関与する (2020)
  • Author(s): 市川佳奈
  • Organizer: 日本眼科学会