Field of Study
Laboratory animal science
Non-human primates, Glaucoma, Age-related macular degeneration, Retinal vein occlusion
Establishment of disease models using non-human primates and development research of new drug
  • 特任教授 角崎 英志 Research Professor Tsusaki Hideshi DVM., Ph.D.
  • 特任講師 大津 航 Research Associate Professor Otsu Wataru DVM., Ph.D. otsu-wa
  • 教授(兼務) 嶋澤 雅光 Professor Shimazawa Masamitsu Ph.D. shimazawa

研究テーマ Research Subjects

「非ヒト霊長類を用いた疾患病態モデルの確立と新薬開発研究」が本研究室の研究テーマです。近年、抗体医薬品をはじめとするバイオ医薬品が数多く開発され、iPS 細胞等を再生医療に応用するための研究開発も盛んになっています。抗体や核酸医薬品の薬効評価は、主要な実験動物である齧歯類ではリガンドとの交差性の問題で評価が難しいことが指摘されています。加えて、齧歯類を用いた病態モデルでは、ヒトとの組織学的な違いや表現形の違いなどが数多く報告されており、よりヒトに近い病態モデル並びにその評価系の需要が高まっています。従って、非ヒト霊長類による病態モデルは、基礎研究から臨床開発の死の谷を越えて医薬品の成功確率を上げるための強力なツールとなり得るため、その開発は社会的にも重要な課題です。本講座では、サルを用いた様々な病態モデルを確立し、その病態解析と薬効評価を行っています。現在、緑内障、加齢黄斑変性及び網膜静脈閉塞症などの網膜疾患の研究を進めています。

"Establishment of disease model using nonhuman primate and translational research for new drug development" is the theme of our research laboratory. Nowadays, more and more biologics such as antibody drug have been developed and used as medicine. On the other hand, research using iPS cells makes remarkable progress for application to regenerative medicine. To evaluate these types of new candidates, the efficacy evaluation system using monkeys gains in importance because conventional models using rodents are not acceptable due to the difference of the cross-reactivity with ligand. Furthermore, since it has come to be indicated that histological morphology and phenotype are not always consistent among human and rodents, monkey seems more suitable to valuate effect and toxicity of candidate compounds. Establishments of disease model and evaluation system using onkeys are potent tools to discover a novel drug which overcomes "Death Valley" between basic research and clinical development. We establish the disease model of monkeys, analyze the pathology and evaluate drug efficacy. Our targets are retinal diseases such as glaucoma, age-related macular degeneration and retinal vein occlusion.

研究課題 Research Objectives

  1. 霊長類を主体とした動物実験モデルの確立及び病態解析
    Establishment and elucidating pathology of animal model using primate
     Studies for establishment and elucidating pathology of exudative age-related macular degeneration and retinal vein occlusion model in monkeys
     Studies for elucidating pathology and evaluation neuroprotective drug of glaucoma model in monkeys
     Study for exploration of biomarkers the above disease models
  2. 確立した動物実験モデルを用いた新薬開発の研究
    Studies for development new drugs using established animal model

最近の研究成果 Research Results

  1. Otsu W., Yako T., Sugisawa E., Nakamura S., Tsusaki H., Umingai N., Shimazawa M., Hara H., Crocetin protects against mitochondrial damage induced by UV-A irradiation in corneal epithelial cell line HCE-T cells. J. Pharm. Sci., 150, 279-288 (2022).
  2. Yako T., Otsu W., Nakamura S., Shimazawa M., Hara H., Lipid Droplet Accumulation Promotes RPE Dysfunction. J. Mol. Sci., 23, 1790 (2022).
  3. Chuang JZ., Yang N., Nakajima N., Otsu W., Fu C,, Yang H., Lee M., Akbar A., Badea T., Guo Z., Nuruzzaman A., Hsu KS., Dunaief J., Sung CH., Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration. Nat. Commun., 13, 375 (2022).
  4. Yako T., Nakamura M., Otsu W., Nakamura S., Shimazawa M., Hara H., Mitochondria dynamics in the aged mice eye and the role in the RPE phagocytosis. Exp. Eye Res., 213, 108800 (2021)
  5. Inagaki S., Shimazawa M., Otsu W., Araki T., Sasaki Y., Numata Y., Nakamura S., Tsusaki H., and Hara H. Creation of retinal vein occlusion model in cynomolgus monkeys and determination of its pathological features. Curr. Neurovasc. Res., 18, 123-133 (2021).