"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
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 ⅰ）サル滲出型加齢黄斑変性及び網膜静脈閉塞症モデルの確立とその病態解明に関する研究 Studies for establishment and elucidating pathology of exudative age-related macular degeneration and retinal vein occlusion model in monkeys ⅱ）サル緑内障モデルを用いた病態解明及び神経保護薬の評価に関する研究 Studies for elucidating pathology and evaluation neuroprotective drug of glaucoma model in monkeys ⅲ）上記疾患モデルのバイオマーカーの探索研究 Study for exploration of biomarkers the above disease models
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
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).
Yako T., Otsu W., Nakamura S., Shimazawa M., Hara H., Lipid Droplet Accumulation Promotes RPE Dysfunction. J. Mol. Sci., 23, 1790 (2022).
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).
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)
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).
