BIOMEDICAL RESEARCH LABORATORY

Gifu Pharmaceutical University

“ESTABLISHMENT OF DISEASE MODEL USING NONHUMAN PRIMATE AND DEVELOPMENT RESEARCH OF NEW DRUG”

Establishments of disease model and evaluation system using monkeys are potent tools to make the drug to overcome “Death Valley”. In our chair, we establish the disease model of monkeys, analyze the pathology and evaluate drug efficacy. We are investigating retinal disease such as glaucoma, age-related macular degeneration and retinal vein occlusion.

CURRENT MEMBERS

Hideshi Tsusaki, DVM., Ph.D.

Research Professor

President, Nonclinical Services

Shin Nippon Biomedical Laboratories, Ltd (SNBL)

Wataru Otsu, DVM., Ph.D.

Research Associate Professor

Curriculum vitae

Graduate student
D1 Mayuna Obayashi

PUBLICATIONS

1. Movement of retinal vessels toward the optic nerve head after increasing intraocular pressure in monkey eyes with experimental glaucoma

Kuroda A., Enomoto N., Ishida K., Shimazawa M., Noguchi T., Horai N., Onoe H., Hara H. and Tomita G.

Exp Eye Res., 162, 110-115, 2017.

2. Relationship between elevated intraocular pressure and divided peripapillary sector retinal nerve fiber layer thickness in a cynomolgus monkey laser-induced ocular hypertension model

Noguchi T., Shimazawa M., Hamaguchi K., Araki T., Horai N. and Hara H.

Ophthalmic Res., 58, 99-106, 2017.

3. Muscle mass measurement by DXA and MRI in non-human primates

Horai N. and Tsusaki H.

Nihon Yakurigaku Zasshi, 152, 126-131, 2018.

4. Establishment of retinal disease models using non-human primates and its strategy for drug discovery

Shimazawa M. and Hara H.

Nihon Yakurigaku Zasshi, 152, 139-146, 2018.

5. Nrf2 activator RS9 suppresses pathological ocular angiogenesis and hyperpermeability

Nakamura S., Noguchi T., Inoue Y., Sakurai S., Nishinaka A., Hida Y., Masuda T., Nakagami Y., Horai N., Tsusaki H., Hara H., and Shimazawa M.

Invest. Ophthalmol. Vis. Sci., 60(6):1943-1952, 2019.

6. The Late Endosomal Pathway Regulates the Ciliary Targeting of Tetraspanin Protein Peripherin 2

Otsu W., Hsu YC., Chuang JZ., and Sung CH.

J. Neurosci., 39(18):3376-3393, 2019.

7. CLIC4 regulates late endosomal trafficking and matrix degradation activity of MMP14 at focal adhesions in RPE cells

*Hsu KS, *Otsu W., Li Y., Wang HC., Chen S., Tsang SH., Chuang JZ., and Sung CH.

Sci. Rep., 9(1):12247, 2019.

*Contributed equally.

8. A triterpenoid Nrf2 activator, RS9, promotes LC3-associated phagocytosis of photoreceptor outer segments in a p62-independent manner

Saito Y., Yako T., Otsu W., Nakamura S., Inoue Y., Muramatsu A., Nakagami Y., Shimazawa M., and Hara H.

Free Radic. Biol. Med.,152:235-247, 2020

9. Blue light-emitting diode irradiation promotes transcription factor EB-mediated lysosome biogenesis and lysosomal cell death in murine photoreceptor-derived cells

Otsu W., Ishida K., Nakamura S., Shimazawa M., Tsusaki H., and Hara H.

Biochem. Biophys. Res. Commun., 526(2):479-484, 2020

10. Anti-vascular endothelial growth factor antibody limits vascular leakage and decreases subretinal fibrosis in a cynomolgus monkey choroidal neovascularization model

Inagaki S., Shimazawa M., Hamaguchi K., Otsu W., Araki T., Sasaki Y., Numata Y., Tsusaki H., and Hara H.

Curr. Neurovasc. Res., 17(4):420-428, 2020

11. Tauroursodeoxycholic acid promotes neuronal survival and proliferation of tissue resident stem and progenitor cells in retina of adult zebrafish

Saito Y., Okuyoshi H., Nakamura S., Otsu W., Yamaguchi A., Hitchcock P.F., Nagashima M, Shimazawa M., and Hara H.

BPB Reports, 3(3), 92-96, 2020

12. Cholesterol-binding protein TSPO2 coordinates maturation and proliferation of terminally differentiating erythroblasts

Kiatpakdee B., Sato K., Otsuka Y., Arashiki N., Chen Y., Tsumita T., Otsu W., Yamamoto A., Kawata R., Yamazaki J., Sugimoto Y., Takada K., Mohandas N., and Inaba M.
J Biol Chem., 295(23):8048-8063, 2020

13. Central nervous system migration of astaxanthin and adonixanthin following their oral administration in cynomolgus monkeys

Nakamura S., Maoka T., Tsuji S., Hayashi M., Shimazawa M., and Hara H.

J. Nutr. Sci. Vitaminol., 66(5):488-494, 2020.

14. Survival motor neuron protein modulates lysosomal function through the expression of transcription factor EB in motoneurons

Ando S., Otsu W., Osanai D., Kamiya S., Ishida K., Nakamura S., Shimazawa M., and Hara H.

BPB Reports, 3(4), 130-137, 2020.

15. Brazilian green propolis promotes the cytoprotective expression of heme oxygenase-1 against oxidative stress injury in murine myoblast cells

Chinen N., Otsu W., Ohuchi K., Ando S., Nakamura S., Kono H., Shimazawa M., and Hara H.

Functional Foods in Health and Disease, 10, 12 (2020)

16. Creation of retinal vein occlusion model in cynomolgus monkeys and determination of its pathological features

Inagaki S., Shimazawa M., Otsu W., Araki T., Sasaki Y., Numata Y., Nakamura S., Tsusaki H., and Hara H.
Curr. Neurovasc. Res., 18(1):123-133, 2021

17. Establishment of a pigmented murine model abundant with characteristics of retinal vein occlusion

Miyagi S., Nishinaka A., Yamamoto T., Otsu W., Nakamura S., Shimazawa M., Kitaoka T., and Hara H.
Exp. Eye Res., 204, 108441, 2021

18. Free-radical scavenger NSP-116 protects the corneal epithelium against UV-A and blue LED light exposure

Ishida K., Yako T., Tanaka M., Otsu W., Nakamura S., Shimazawa M., Tsusaki H., and Hara H.

Biol. Pharm. Bull., 44(7):937-946, 2021.

19. Progranulin deficiency in Iba-1+ myeloid cells exacerbates choroidal neovascularization by perturbation of lysosomal function and abnormal inflammation

Takahashi K., Nakamura S., Otsu W., Shimazawa M., and Hara H.

J. Neuroinflamm., 18(1), 164, 2021.

20. Cigarette smoke extract and heated tobacco products promote ferritin cleavage and iron accumulation in human corneal epithelial cells

Otsu W., Ishida K., Chinen N., Nakamura S., Shimazawa M., Tsusaki H., and Hara H.

Sci. Rep., 11(1):18555, 2021.

21. Mitochondria dynamics in the aged mice eye and the role in the RPE phagocytosis

Yako T., Nakamura M., Otsu W., Nakamura S., Shimazawa M., and Hara H.

Exp. Eye Res., 213, 108800, 2021.

22. Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration

*Chuang JZ., *Yang N., *Nakajima N., *Otsu W., Fu C., Yang HH., Lee MP., Akbar AF., Bdea TC., Guo Z., Nuruzzaman A., Hsu KS., Dunaief JL., and Sung CH.

Nat. Commun., 13(1):375, 2022.

*Contributed equally

23. Lipid droplet accumulation promotes RPE dysfunction

Yako T., Otsu W., Nakamura S., Shimazawa M., and Hara H.

Int. J. Mol. Sci., 23(3): 1790, 2022.

24. The pathological association between the anterior eye segment and the retina in a murine model of neovascular glaucoma

Nishinaka A., Tanaka M., Aoshima K., Kuriyama A., Sasaki T., Otsu W., Yasuda H., Nakamura S., Shimazawa M., and Hara H.

FASEB J., 36(6):e22323, 2022.

25. Crocetin protects against mitochondrial damage induced by UV-A irradiation in corneal epithelial cell line HCE-T cells

Otsu W., Yako T., Sugisawa E., Nakamura S., Tsusaki H., Umigai N., Shimazawa M., and Hara H.

J. Pharmacol. Sci., 150(4):279-288, 2022.

26. Blueberry stem extract suppresses blue light emitting diode light induced endoplasmic reticulum stress on retinal photoreceptor cells

Ogawa K., Karitani T, Otsu W., Nishiyama K., Kunitake H., Goto Y., Nomiyama S., Hara H., and Yamasaki M.

BPB Reports, 6(3), 87-97, 2023.

27. Protective effect of Vaccinium myrtillus L. extract against UVA-induced injury in ARPE-19 cells

Otsu W., Hara H., and Ogawa K.

Food Sci. Technol. Res. 29 (5), 403-411, 2023.

28. Protective effect of crocetin against cytoskeletal injury induced by acrolein from cigarette smoke extract in C2C12 myoblasts

Otsu W., Chinen N., Sugisawa E., Kitano H., Nakamura S., Umigai N., Tsusaki H., and Shimazawa M.

J. Funct. Foods, 106, 105611, 2023.

29. Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets

Saito M., Otsu W., Miyadera K., and Nishimura Y.

Front. Mol. Biosci., 10, 1232188, 2023.

30. Delphinidins from Maqui berry (Aristotelia chilensis) ameliorate the subcellular organelle damage induced by blue light exposure in murine photoreceptor-derived cells

Yamazaki K., Ishida K., Otsu W., Muramatsu A., Nakamura S., Yamada W., Tsusaki H., Shimoda H., Hara H., and Shimazawa M.

BMC Complement. Med. Ther., 24(3), 2024

31. Investigation into the usefulness of cynomolgus monkeys with spontaneously elevated intraocular pressure as a model for glaucoma treatment research

Araki T., Shimazawa M., Nakamura S., Otsu W., Numata Y, Sakata M., Kabayama K., Tsusaki H., and Hara H.

J. Pharmacol. Sci. 154(2), 52-60, 2024.

32. Mutant mice with rod-specific VPS35 deletion exhibit retinal α-synuclein pathology-associated retinal degeneration

Fu C., Yang N., Chuang JZ., Nakajima N., Iraha S., Roy N., Wu Z., Jiang Z., Otsu W., Radu RA., Yang HH., Lee MP., Worgall TS., Xiong WC, and Sung CH.

Nat. Commun.,15(1):5970, 2024.

33. Intranasal administration of liposomes can deliver drugs to the posterior ophthalmic region in addition to the brain

Tsuji S., Hatano R., Nakamura S., Kudo U., Aoshima K., Fujimori H., Takagi Y., Obayashi M., Ito T., Yamazoe E., KuseY., Otsu W., Shimazawa M., Tahara K.

J. Drug Deliv. Sci. Technol.,101, 106254, 2024.

34. NAMPT activator P7C3-A20 protects against tunicamycin-induced cell injury in C2C12 murine myoblast cells

Chinen N., Otsu W., Kuse Y., Nakamura S., Hara H., Shimazawa M.

BPB Reports, 7(6), 212-217, 2024

35. Macular white dot lesions with hyperreflective optical coherence tomography findings in cynomolgus and rhesus monkeys