Development of new drugs for direct reprogramming into corneal epithelial cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16930
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kitazawa Koji 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10760803)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: ダイレクトリプログラミング / 角膜上皮 / 転写因子 / 低分子化合物

Outline of Final Research Achievements

We firstly, analyzed mircroarray data of corneal epithelial cells and epidermal keratinocyte, which is a model showing the pathological condition on the severe ocular surface disorders, such as Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and severe thermal/chemical injury, and 8877 of small molecular compounds, which enhanced the corneal related genes, were selected. Using CMap data base, candidate compounds were narrowed down. Among them, 13 candidate were found with more than 90 of score, and 48 candidates were observed with less than 90 of score, indicating the possible induction of corneal-related gene expression profile. However, no small molecule compounds were capable of reprogramming into corneal epithelial cells was found, although the treatment period and the combination of compounds were tested by various conditions,

Free Research Field

医薬

Academic Significance and Societal Importance of the Research Achievements

本研究では、網羅的遺伝子発現のデータを用いて、低分子化合物で角膜上皮細胞へのリプログラミングを可能とする薬剤開発を目指したが、結果的に本法では有力な候補薬剤を同定することはできなかった。しかし、本研究から得られたデータによって、化合物スクリーニング方法の改善など、さらなる研究の発展に貢献することができる。