Development of new treatments for refractory corneal stroma incision injury in TRPV1 and TRPA1 control

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16931
• 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: Nidegawa Yuka 和歌山県立医科大学, 医学部, 博士研究員 (50727807)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 角膜実質 / 創傷治癒 / TRPチャネル

Outline of Final Research Achievements

The loss of Trpv1 gene delayed closure of corneal stromal incision with hindered myofibroblast transdifferentiation along with declines in the expression of collagen Ia1 and TGFβ1. Inflammatory cell infiltration was not affected by the loss of TRPV1. Ultrastructurally endoplasmic reticulum of TRPV1-null keratocytes was more extensively dilated as compared with WT keratocytes, suggesting an impairment of protein secretion by TRPV1-gene knockout. These results indicate that injury-related TRPV1 signal is involved in healing of stromal incision injury in a mouse cornea by selectively stimulating TGFβ-induced granulation tissue formation.

Free Research Field

角膜

Academic Significance and Societal Importance of the Research Achievements

角膜では外傷後の治癒過程での線維・瘢痕化は透明性と形状異常を惹起し、視機能を低下させる。速やかな創傷治癒による炎症軽減と線維瘢痕化抑制が透明性と形状の維持に必須であるが、一方で治癒後の強度維持も担保される必要がある。本研究により、TRPV1KOマウス角膜では、角膜実質治癒過程でのTGFβ1発現の抑制により、筋線維芽細胞やコラーゲンの発現が抑制されることが考えられ、TRPV1は角膜実質での創傷治癒促進・線維瘢痕化に関わる因子である可能性が示唆され、新たな角膜創傷治癒の治療方法にTRPV1をコントロールする治療薬という選択肢が考えられた。