Kurihara, Toshihide

写真a

Affiliation

School of Medicine, Department of Ophthalmology (Shinanomachi)

Position

Assistant Professor/Senior Assistant Professor

Profile 【 Display / hide

  • Toshihide Kurihara is an Associate Professor of Ophthalmology at Keio University, Tokyo, Japan. He has also been appointed as an Adjunct Assistant Professor at the Scripps Research Institute (TSRI) in La Jolla, CA, USA. He received his M.D. degree from the Faculty of Medicine, University of Tsukuba, Ibaraki, Japan, in 2001. He completed his ophthalmology residency at Keio University Hospital in 2005, and obtained his Ph.D. degree under the supervision of Professor Kazuo Tsubota from Keio University Graduate School of Medicine in 2009. Dr. Kurihara did his postdoctoral training under the mentorship of Professor Martin Friedlander at TSRI. His research interest is hypoxia responses in development, physiology, and pathophysiology of the retina. Editorial Board Member: BioMed Research International, Journal of Ophthalmology, and Case Reports in Ophthalmological Medicine

Career 【 Display / hide

  • 2001.04
    -
    2003.03

    Keio University Hospital, Department of Ophthalmology, Resident

  • 2002.07
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    2003.06

    National Kasumigaura Hospital, Department of Ophthalmology, Resident

  • 2003.04
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    2004.03

    Keio University Hospital, Department of Ophthalmology, Clinical Fellow

  • 2004.01
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    2005.03

    Tokyo Saiseikai Central Hospital, Ophthalmology, Clinical Fellow

  • 2005.04
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    2009.03

    Keio University Graduate School of Medicine, Doctoral Course

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Academic Background 【 Display / hide

  • 1995.04
    -
    2001.03

    University of Tsukuba, School of Medicine

    University, Graduated

  • 2005.04
    -
    2009.03

    Keio University, Graduate School of Medicine

    Graduate School, Completed

Academic Degrees 【 Display / hide

  • 博士(医学), 慶應義塾大学, Coursework, 2009.03

 

Papers 【 Display / hide

  • Spatial Functional Characteristics of East Asian Patients With Occult Macular Dystrophy (Miyake Disease); EAOMD Report No. 2

    Yang L., Joo K., Tsunoda K., Kondo M., Fujinami-Yokokawa Y., Arno G., Pontikos N., Liu X., Nakamura N., Kurihara T., Tsubota K., Iwata T., Li H., Zou X., Wu S., Sun Z., Ahn S.J., Kim M.S., Mun Y.S., Park K.H., Robson A.G., Miyake Y., Woo S.J., Sui R., Fujinami K.

    American Journal of Ophthalmology (American Journal of Ophthalmology)  221   169 - 180 2021.01

    ISSN  00029394

     View Summary

    © 2020 The Authors Purpose: To describe the functional phenotypic features of East Asian patients with RP1L1-associated occult macular dystrophy (ie, Miyake disease). Design: An international multicenter retrospective cohort study. Methods: Twenty-eight participants (53 eyes) with Miyake disease were enrolled at 3 centers (in Japan, China, and South Korea). Ophthalmologic examinations including spectral-domain optical coherence tomography (SDOCT) and multifocal electroretinogram (mfERG) were performed. Patients were classified into 3 functional groups based on mfERG: Group 1, paracentral dysfunction with relatively preserved central/peripheral function; Group 2, homogeneous central dysfunction with preserved peripheral function; and Group 3, widespread dysfunction over the recorded area. Three functional phenotypes were compared in clinical parameters and SDOCT morphologic classification (severe phenotype, blurred/flat ellipsoid zone and absence of the interdigitation zone; mild phenotype, preserved ellipsoid zone). Results: There were 8 eyes in Group 1, 40 eyes in Group 2, and 5 eyes in Group 3. The patients in Group 1 showed significantly later onset (P =.005) and shorter disease duration (P =.002), compared with those in Group 2. All 8 eyes in Group 1 showed the mild morphologic phenotype, while 43 of 45 eyes in Groups 2 and 3 presented the severe phenotype, which identified a significant association between the functional grouping and the morphologic classification (P <.001). Conclusions: A spectrum of functional phenotypes of Miyake disease was first documented with identification of 3 functional subtypes. Patients with paracentral dysfunction had the mildest phenotype, and those with homogeneous central or widespread dysfunction showed overlapping clinical findings with severe photoreceptor changes, suggesting various extents of visual impairment.

  • Rice bran and vitamin b6 suppress pathological neovascularization in a murine model of age‐related macular degeneration as novel hif inhibitors

    Ibuki M., Lee D., Shinojima A., Miwa Y., Tsubota K., Kurihara T.

    International Journal of Molecular Sciences (International Journal of Molecular Sciences)  21 ( 23 ) 1 - 24 2020.12

    ISSN  16616596

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    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age‐related macular degeneration (AMD) in the elderly. Inhibiting neovascularization via antivascular endothelial growth factor (VEGF) drugs has been used for the effective treatment. However, anti‐VEGF therapies may cause development of chorioretinal atrophy as they affect a physiological amount of VEGF essential for retinal homeostasis. Furthermore, anti‐VEGF therapies are still ineffective in some cases, especially in patients with AMD. Hypoxia‐inducible factor (HIF) is a strong regulator of VEGF induction under hypoxic and other stress conditions. Our previous reports have indicated that HIF is associated with pathological retinal neovascularization in murine models of ROP and AMD, and HIF inhibition suppresses neovascularization by reducing an abnormal increase in VEGF expression. Along with this, we attempted to find novel effective HIF inhibitors from natural foods of our daily lives. Food ingredients were screened for prospective HIF inhibitors in ocular cell lines of 661W and ARPE‐19, and a murine AMD model was utilized for examining suppressive effects of the ingredients on retinal neovascularization. As a result, rice bran and its component, vitamin B6 showed inhibitory effects on HIF activation and suppressed VEGF mRNA induction under a CoCl2‐induced pseudo-hypoxic condition. Dietary supplement of these significantly suppressed retinal neovascularization in the AMD model. These data suggest that rice bran could have promising therapeutic values in the management of pathological ocular neovascularization.

  • Relationship between nerve fiber layer defect and the presence of epiretinal membrane in a Japanese population: The JPHC-NEXT Eye Study

    Uchida A., Sasaki M., Motomura K., Yuki K., Kurihara T., Tomita Y., Ozawa Y., Yamagishi K., Kawasaki R., Hanyuda A., Sawada N., Tsubota K., Tsugane S., Iso H.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

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    © 2020, The Author(s). The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.

  • Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder: Identification of Genotype-phenotype Association

    Fujinami-Yokokawa Y., Fujinami K., Kuniyoshi K., Hayashi T., Ueno S., Mizota A., Shinoda K., Arno G., Pontikos N., Yang L., Liu X., Sakuramoto H., Katagiri S., Mizobuchi K., Kominami T., Terasaki H., Nakamura N., Kameya S., Yoshitake K., Miyake Y., Kurihara T., Tsubota K., Miyata H., Iwata T., Tsunoda K., Nishimura T., Hayashizaki Y., Kondo M., Shimozawa N., Horiguchi M., Yamamoto S., Kuze M., Naoi N., Machida S., Shimada Y., Nakamura M., Fujikado T., Hotta Y., Takahashi M., Mochizuki K., Murakami A., Kondo H., Ishida S., Nakazawa M., Hatase T., Matsunaga T., Maeda A., Noda K., Tanikawa A., Yamamoto S., Yamamoto H., Araie M., Aihara M., Nakazawa T., Sekiryu T., Kashiwagi K., Kosaki K., Piero C., Fukuchi T., Hayashi A., Hosono K., Mori K., Tanaka K., Furuya K., Suzuki K., Kohata R., Yanagi Y., Minegishi Y., Iejima D., Suga A., Rossmiller B.P., Pan Y., Oshima T., Nakayama M., Teruyama Y., Yamamoto M., Minematsu N., Sanbe H., Mori D., Kijima Y., Mawatari G., Kurata K., Yamada N., Itoh M., Kawaji H., Murakawa Y.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

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    © 2020, The Author(s). Inherited retinal disorder (IRD) is a leading cause of blindness, and CRX is one of a number of genes reported to harbour autosomal dominant (AD) and recessive (AR) causative variants. Eighteen patients from 13 families with CRX-associated retinal disorder (CRX-RD) were identified from 730 Japanese families with IRD. Ophthalmological examinations and phenotype subgroup classification were performed. The median age of onset/latest examination was 45.0/62.5 years (range, 15–77/25–94). The median visual acuity in the right/left eye was 0.52/0.40 (range, −0.08–2.00/−0.18–1.70) logarithm of the minimum angle of resolution (LogMAR) units. There was one family with macular dystrophy, nine with cone-rod dystrophy (CORD), and three with retinitis pigmentosa. In silico analysis of CRX variants was conducted for genotype subgroup classification based on inheritance and the presence of truncating variants. Eight pathogenic CRX variants were identified, including three novel heterozygous variants (p.R43H, p.P145Lfs*42, and p.P197Afs*22). A trend of a genotype-phenotype association was revealed between the phenotype and genotype subgroups. A considerably high proportion of CRX-RD in ADCORD was determined in the Japanese cohort (39.1%), often showing the mild phenotype (CORD) with late-onset disease (sixth decade). Frequently found heterozygous missense variants located within the homeodomain underlie this mild phenotype. This large cohort study delineates the disease spectrum of CRX-RD in the Japanese population.

  • Genetic Spectrum of EYS-associated Retinal Disease in a Large Japanese Cohort: Identification of Disease-associated Variants with Relatively High Allele Frequency

    Yang L., Fujinami K., Ueno S., Kuniyoshi K., Hayashi T., Kondo M., Mizota A., Naoi N., Shinoda K., Kameya S., Fujinami-Yokokawa Y., Liu X., Arno G., Pontikos N., Kominami T., Terasaki H., Sakuramoto H., Katagiri S., Mizobuchi K., Nakamura N., Mawatari G., Kurihara T., Tsubota K., Miyake Y., Yoshitake K., Iwata T., Tsunoda K., Nishimura T., Hayashizaki Y., Shimozawa N., Horiguchi M., Yamamoto S., Kuze M., Machida S., Shimada Y., Nakamura M., Fujikado T., Hotta Y., Takahashi M., Mochizuki K., Murakami A., Kondo H., Ishida S., Nakazawa M., Hatase T., Matsunaga T., Maeda A., Noda K., Tanikawa A., Yamamoto S., Yamamoto H., Araie M., Aihara M., Nakazawa T., Sekiryu T., Kashiwagi K., Kosaki K., Piero C., Fukuchi T., Hayashi A., Hosono K., Mori K., Tanaka K., Furuya K., Suzuki K., Kohata R., Yanagi Y., Minegishi Y., Iejima D., Suga A., Rossmiller B.P., Pan Y., Oshima T., Nakayama M., Yamamoto M., Minematsu N., Mori D., Kijima Y., Kurata K., Yamada N., Itoh M., Kawaji H., Murakawa Y.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

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    © 2020, The Author(s). Biallelic variants in the EYS gene are a major cause of autosomal recessive inherited retinal disease (IRD), with a high prevalence in the Asian population. The purpose of this study was to identify pathogenic EYS variants, to determine the clinical/genetic spectrum of EYS-associated retinal disease (EYS-RD), and to discover disease-associated variants with relatively high allele frequency (1%-10%) in a nationwide Japanese cohort. Sixty-six affected subjects from 61 families with biallelic or multiple pathogenic/disease-associated EYS variants were ascertained by whole-exome sequencing. Three phenotype groups were identified in EYS-RD: retinitis pigmentosa (RP; 85.94%), cone-rod dystrophy (CORD; 10.94%), and Leber congenital amaurosis (LCA; 3.12%). Twenty-six pathogenic/disease-associated EYS variants were identified, including seven novel variants. The two most prevalent variants, p.(Gly843Glu) and p.(Thr2465Ser) were found in 26 and twelve families (42.6%, 19.7%), respectively, for which the allele frequency (AF) in the Japanese population was 2.2% and 3.0%, respectively. These results expand the phenotypic and genotypic spectrum of EYS-RD, accounting for a high proportion of EYS-RD both in autosomal recessive RP (23.4%) and autosomal recessive CORD (9.9%) in the Japanese population. The presence of EYS variants with relatively high AF highlights the importance of considering the pathogenicity of non-rare variants in relatively prevalent Mendelian disorders.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

Presentations 【 Display / hide

  • 増殖糖尿病網膜症に併発した黄斑円孔に対する内境界膜剥離

    栗原俊英、野田航介、永井紀博、今村裕、石田晋、井上真

    第42回日本網膜硝子体学会 (福岡) , 2003.12

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 低酸素応答を標的とした予防から治療までを網羅する網膜疾患制御技術開発

    2018.04
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    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 栗原 俊英, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • Approach for retinal diseases based on regulation of hypoxia response

    2015.04
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    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 栗原 俊英, Grant-in-Aid for Scientific Research (C), Principal Investigator

Awards 【 Display / hide

  • 第23回ROHTO AWARD

    2018.04, ロート製薬株式会社, 低酸素応答を基軸としたトランスレーショナルリサーチの推進

  • 2016年度日本抗加齢医学会研究奨励賞

    2016.06, 日本抗加齢医学会, 低酸素応答の加齢黄斑変性における役割

  • 平成28年度三四会賞「北里賞」

    2016.06, 慶應義塾大学医学部, 網膜の発生と病態生理における低酸素応答の役割

  • 第8回田野Young Investigator's Award

    2015.12, 日本網膜硝子体学会

  • IMC International Travel Grant

    2015.09, International Myopia Conference, An association of serum vitamin D level with myopia initiation by UV exposure in chick

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