Development of novel therapeutics targetingTRP channel for neurotrophic keratopathy

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10878
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Wakayama Medical University
• Principal Investigator: OKADA YUKA 和歌山県立医科大学, 医学部, 准教授 (50264891)
• Co-Investigator(Kenkyū-buntansha): 雑賀 司珠也 和歌山県立医科大学, 医学部, 教授 (40254544)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 神経麻痺性角膜症 / TRPチャネル

Outline of Final Research Achievements

A mouse model of neurotrophic keratopathy was produced in the cranium by using a needle at the point described above, a bipolar coagulation. Sensory loss was confirmed by the lack of the blink reflex on air jet stimulation as well as by confirming less response with cochet-bonnet aesthesiometer. The cornea of a mouse following electrolysis coagulation of the first branch of the trigeminal nerve showed significant delayed epithelial defect closure. TRPV4 gene introduction into a damaged V1 nerve rescues the impairment of epithelial healing.The system composed of sensory nerve TRPV4 - maintenance of cell stemness - NGFn is one of the major mechanisms of homeostasis of corneal epithelium.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

神経麻痺性角膜症は、三叉神経第１枝領域が障害され角膜知覚が低下することで角膜障害と角膜創傷治癒遅延が惹起される疾患であるが、病態解明が不十分でそれに基づく根治的な治療法はない。角膜保護剤や抗生剤点眼などの対症療法のみできわめて難治性である。
知覚神経麻による神経終末からの神経ペプチドが病態に大きく関与していると想定する中、それらの神経ペプチドの分泌に関与するTRPV4を障害三叉神経で強制発現させることがの神経麻痺性角膜症の治療標的となる可能性を示せた。