Ophthalmological and systemic investigations of autosomal dominant optic atrophy with OPA1 mutations.

• Project/Area Number: 26462674
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: Tsunoda Kazushige 独立行政法人国立病院機構(東京医療センター臨床研究センター), その他部局等, 部長 (30255525)
• Co-Investigator(Kenkyū-buntansha): 林 孝彰 東京慈恵会医科大学, 医学部, 講師 (10297418)
• Research Collaborator: 大出 尚郎 慶應義塾大学 ; 松永 達雄 東京医療センター ; 安富 大祐 東京医療センター
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 優性視神経萎縮症 / OPA1 / 常染色体優性視神経萎縮症 / DOA-Plus disease / Auditory Neuropathy / OPA1遺伝子

Outline of Final Research Achievements

We have investigated systemic complications of autosomal dominant optic atrophy (DOA) in the JEGC cohort with 30 institutes. Three cases with DOA-plus disease were included, and all of them had AN. One case had both ataxia and progressive extraocular ophthalmoplegia. In the genetic analysis of 31 cases with all the DOA in National Institute of Sensory Organs and Jikei medical school, type of variants was either missense, nonsense, splice-site, or in-del. However, Patients with DOA-plus harbored only missense mutations.

Research Products

• [Journal Article] Heterozygous deletion of the OPA1 gene in patients with dominant optic atrophy. (2017)
  • Author(s): Hayashi T, Sasano H, Katagiri S, Tsunoda K, Kameya S, Nakazawa M, Iwata T, Tsuneoka H.
  • Journal Title: Jpn J Ophthalmol. Volume: 61 Issue: 5 Pages: 483-488
  • DOI: 10.1007/s10384-017-0522-0
  • Peer Reviewed
• [Journal Article] Parafoveal Photoreceptor Abnormalities in Asymptomatic Patients With RP1L1 Mutations in Families With Occult Macular Dystrophy. (2017)
  • Author(s): Kato Y, Hanazono G, Fujinami K, Hatase T, Kawamura Y, Iwata T, Miyake Y, Tsunoda K.
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 58(14) Issue: 14 Pages: 6020-6029
  • DOI: 10.1167/iovs.17-21969
  • Peer Reviewed
• [Journal Article] Evaluation of cone function by a handheld non-mydriatic flicker electroretinogram device (2016)
  • Author(s): Natsuko Nakamura, Kaoru Fujinami, Yoshinobu Mizuno, Toru Noda, Kazushige Tsunoda
  • Journal Title: Clinical Ophthalmology Volume: 10 Pages: 1175-85
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel heterozygous splice site OPA1 mutation causes exon 10 skipping in Japanese patients with dominant optic atrophy (2016)
  • Author(s): Iida K, Ohkuma Y, Hayashi T, Katagiri S, Fujita T, Tsunoda K，Yamada H, Tsuneoka H
  • Journal Title: Ophthalmic Genet Volume: 37 Pages: 354-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel mutations in the gene for α-subunit of retinal cone cyclic nucleotide-gated channels in a Japanese patient with congenital achromatopsia. (2016)
  • Author(s): Kuniyoshi K, Muraki-Oda S, Ueyama H, Toyoda F, Sakuramoto H, Ogita H, Irifune M, Yamamoto S, Nakao A, Tsunoda K, Iwata T, Ohji M, Shimomura Y.
  • Journal Title: Jpn J Ophthalmol Volume: 60 Issue: 3 Pages: 187-197
  • DOI: 10.1007/s10384-016-0424-6
  • Peer Reviewed / Open Access
• [Journal Article] Association of Retinal Artery and Other Inner Retinal Structures With Distribution of Tapetal-like Reflex in Oguchi's Disease. (2015)
  • Author(s): Kato Y, Tsunoda K, Fujinami K, Iwata T, Saga M, Oguchi Y.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: Apr;56(4) Issue: 4 Pages: 2162-72
  • DOI: 10.1167/iovs.14-16198
  • Peer Reviewed
• [Journal Article] Occult macular dystrophy (2015)
  • Author(s): Miyake Y and Tsunoda K
  • Journal Title: Japanese Journal of Ophthalmology Volume: 59(2): Issue: 2 Pages: 71-80
  • DOI: 10.1007/s10384-015-0371-7
  • NAID: 40020401023
• [Journal Article] Congenital Achromatopsia and Macular Atrophy Caused by a Novel Recessive PDE6C Mutation (p.E591K). (2015)
  • Author(s): Katagiri S, Hayashi T, Yoshitake K, Sergeev Y, Akahori M, Furuno M, Nishino J, Ikeo K, Tsunoda K, Tsuneoka H, Iwata T.
  • Journal Title: Ophthalmic Genet. Volume: Jun;36(2) Issue: 2 Pages: 137-44
  • DOI: 10.3109/13816810.2014.991932
  • Peer Reviewed
• [Journal Article] Reduced rod electroretinograms in carrier parents of two Japanese siblings with autosomal recessive retinitis pigmentosa associated with PDE6B gene mutations. (2015)
  • Author(s): Kuniyoshi K, Sakuramoto H, Yoshitake K, Ikeo K, Furuno M, Tsunoda K, Kusaka S, Shimomura Y, Iwata T.
  • Journal Title: Doc Ophthalmol. Volume: Aug;131(1) Issue: 1 Pages: 71-9
  • DOI: 10.1007/s10633-015-9497-7
  • Peer Reviewed
• [Journal Article] Pathologic Changes of Cone Photoreceptors in Eyes With Occult Macular Dystrophy. (2015)
  • Author(s): Nakanishi A, Ueno S, Kawano K, Ito Y, Kominami T, Yasuda S, Kondo M, Tsunoda K, Iwata T, Terasaki H.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: Nov;56(12) Issue: 12 Pages: 7243-9
  • DOI: 10.1167/iovs.15-16742
  • Peer Reviewed / Open Access
• [Journal Article] オカルト黄斑ジストロフィ（三宅病) (2015)
  • Author(s): 角田和繁
  • Journal Title: 日本の眼科 Volume: 86 (8) Pages: 48-49
  • NAID: 10029525854
• [Journal Article] 卵黄様黄斑ジストロフィ (2015)
  • Author(s): 角田和繁
  • Journal Title: 眼科 Volume: 57 (4) Pages: 641-645
• [Journal Article] Clinical and Molecular Characteristics of Childhood-onset Stargardt Disease. (2015)
  • Author(s): Fujinami K, Jana Zernant, Ravinder K Chana, Genevieve A Wright, Tsunoda K, Ozawa Y, Tsubota K, Anthony G Robson, Graham E Holder, Rando Allikmets, Michel Michaelides, FACS; Anthony T Moore.
  • Journal Title: Ophthalmology. Volume: 122 Issue: 2 Pages: 326-334
  • DOI: 10.1016/j.ophtha.2014.08.012
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel nonsense and splice site mutations in CRB1 gene in two Japanese patients with early-onset retinal dystrophy Documenta Ophthalmologica. (2015)
  • Author(s): Kuniyoshi K, Ikeo K, Sakuramoto H, Furuno M, Yoshitake K, Hatsukawa Y, Nakao A, Kusaka S, Shimomura Y, Iwata T.
  • Journal Title: Documenta Ophthalmologica Volume: 130 Issue: 1 Pages: 49-55
  • DOI: 10.1007/s10633-014-9464-8
  • Peer Reviewed
• [Journal Article] Congenital achromatopsia and macular atrophy caused by a novel recessive PDE6C mutation (p.E591K) (2015)
  • Author(s): Satoshi Katagiri, Takaaki Hayashi, Kazutoshi Yoshitake, Yuri Sergeev, Masakazu Akahori, Masaaki Furuno, Jo Nishino, Kazuho Ikeo, Kazushige Tsunoda, Hiroshi Tsuneoka, and Takeshi Iwata
  • Journal Title: Ophthalmic Genetics Volume: 21 Pages: 1-8
• [Journal Article] Longitudinal clinical course of three Japanese patients with Leber congenital amaurosis/early onset retinal dystrophy with RDH12 mutation (2014)
  • Author(s): Kazuki Kuniyoshi, Hiroyuki Sakuramoto, Kazutoshi Yoshitake, Kosuke Abe, Kazuho Ikeo, Masaaki Furuno, Kazushige Tsunoda, Shunji Kusaka, Yoshikazu Shimomura, Takeshi Iwata
  • Journal Title: Documenta Ophthalmologica Volume: Volume 128, Issue 3, Issue: 3 Pages: 219-228
  • DOI: 10.1007/s10633-014-9436-z
• [Journal Article] Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa (2014)
  • Author(s): Katagiri S, Akahori M, Sergeev Y, Yoshitake K, Ikeo K, Furuno M, Hayashi T, Kondo M, Ueno S, Tsunoda K, Shinoda K, Kuniyoshi K, Tsurusaki Y, Matsumoto N, Tsuneoka H, Iwata T.
  • Journal Title: Plos One Volume: 9（9） Issue: 9 Pages: e108721-e108721
  • DOI: 10.1371/journal.pone.0108721
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical course of focal choroidal excavation in Vogt-Koyanagi-Harada disease. (2014)
  • Author(s): Nishikawa Y, Fujinami K, Watanabe K, Noda T, Tsunoda K, Akiyama K.
  • Journal Title: Clin Ophthalmol. Volume: 8 Pages: 2461-5
  • DOI: 10.2147/opth.s75558
  • Peer Reviewed
• [Journal Article] Fundus auofluorescence imaging in patient with juvenile form of galactosialidosis (2014)
  • Author(s): Yamazaki R, Tsunoda K, Fujinami K, Noda T et al.
  • Journal Title: Ophthalmic Surgery Lasers & Imaging Retina Volume: in press Issue: 3 Pages: 259-61
  • DOI: 10.3928/23258160-20140425-01
  • Peer Reviewed
• [Presentation] Auditory neuropathyを合併した常染色体優性視神経萎縮症の3例 (2017)
  • Author(s): 前田亜希子, 中村奈津子, 藤波芳, 野田徹, 松永達雄, 加我君孝, 林孝彰, 冲永聡子, 角田和繁
  • Organizer: 第65回日本臨床視覚電気生理学会
• [Presentation] OPA1遺伝子欠失を認めた常染色体優性視神経萎縮の家系 (2016)
  • Author(s): 林孝彰、笹野紘之、吉田希望、片桐聡、角田和繁、常岡寛
  • Organizer: 第70回日本臨床眼科学会
  • Place of Presentation: 京都
• [Presentation] RETeval Complete™により診断に至った遺伝性網膜疾患の小児例 (2015)
  • Author(s): 中村奈津子、玉置惣一朗、野田徹、藤波芳、角田和繁
  • Organizer: 第63回日本臨床視覚電気生理学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-08-29
• [Presentation] Japan whole exome project for inherited retinal diseases 2014 (2015)
  • Author(s): 藤波芳、林孝彰、國吉一樹、近藤峰生、上野真治、篠田啓、坪田一男、岩田岳、三宅養三、角田和繁
  • Organizer: 第63回日本臨床視覚電気生理学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-08-29
• [Presentation] ‘Screening of cone dysfunction by a handheld ERG device, RETevalTM.’ (2015)
  • Author(s): Tamaki S, Nakamura N, Mizuno Y, Noda T, Fujinami K, Tsunoda K.
  • Organizer: ISCEV symposium 2015 (International Society for Clinical Electrophysiology of Vision)
  • Place of Presentation: Ljubljana, Slovenia
  • Year and Date: 2015-07-22
  • Int'l Joint Research
• [Presentation] Japan whole exome project for inherited retinal diseases 2014 (2015)
  • Author(s): Fujinami K, Hayashi T, Kuniyoshi K, Kondo M, Ueno S, Shinoda K, Tsubota K, Miyake Y, Tsunoda K, Iwata T.
  • Organizer: ISCEV symposium 2015 (International Society for Clinical Electrophysiology of Vision)
  • Place of Presentation: Ljubljana, Slovenia
  • Year and Date: 2015-07-22
  • Int'l Joint Research
• [Presentation] Japan Whole Exome Project for Inherited Retinal Diseases 2014 (2015)
  • Author(s): Fujinami K, Hayashi T, Kuniyoshi K, Kondo M, Ueno S, Shinoda K, Tsubota K, Miyake Y, Tsunoda K, Iwata T.
  • Organizer: ARVO annual meeting 2015 (The Association for Research in Vision and Ophthalmology)
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2015-05-03
  • Int'l Joint Research
• [Presentation] 「遺伝性網膜疾患、最新のgenotyping」 「オカルト黄斑ジストロフィー」 (2014)
  • Author(s): 角田和繁
  • Organizer: 第62回日本臨床視覚電気生理学会
  • Place of Presentation: 東京都墨田区
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] 中心窩機能温存型黄斑ジストロフィ (2014)
  • Author(s): 藤波芳、後藤聡、赤堀正和、小沢洋子、坪田一男、野田徹、岩田岳、三宅養三、角田和繁
  • Organizer: 第62回日本臨床視覚電気生理学会
  • Place of Presentation: 東京都墨田区
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] Unilateral Cone-rod Dysfunction associated with Electronegative bright flash Electroretinography (2014)
  • Author(s): Toshihiko Hirakata, Kaoru Fujinami, Yu Kato, Natsuko Nakamura, Toru Noda, Akito Hirakata, Shinji Ueno, Hiroshi Ohguro, Yozo Miyake, Kazushige Tsunoda
  • Organizer: ISCEV
  • Place of Presentation: Boston,USA
  • Year and Date: 2014-07-21 – 2014-07-24
• [Presentation] Clinical and Genetic Characteristics of Childhood-onset Stargardt Disease. (2014)
  • Author(s): Fujinami K, Zernant J, Ozawa Y, Tsunoda K, Tsubota K, Robson AG,, Alikmets R, Michaelides M, Moore AT, Holder GE
  • Organizer: ISCEV
  • Place of Presentation: Boston,USA
  • Year and Date: 2014-07-21 – 2014-07-24
• [Presentation] Novel funduscopic features in patients with Oguchi’s disease. (2014)
  • Author(s): Kato Y, Tsunoda K, Fujinami K, Noda T, Oguchi Y.
  • Organizer: ISCEV
  • Place of Presentation: Boston,USA
  • Year and Date: 2014-07-21 – 2014-07-24
• [Presentation] Observations of cone photoreceptor by adaptive optics fundus camera in eyes with occult macular dystrophy (2014)
  • Author(s): Nakanishi A, Ueno S, Kawano K, Ito Y, Tsunoda K, Akahori M, Iwata T, Terasaki H
  • Organizer: ARVO 2014 Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2014-05-04 – 2014-05-08
• [Presentation] Efficacy of Aflibercept in Japanese Patients with Polypoidal Choroidal Vasculopathy Insensitive to Ranibizumab Treatment (poster). (2014)
  • Author(s): Toshiaki Hirakata, Yuko Nishikawa, Kaoru Fujinami, Ken Watanabe, Kazushige Tsunoda, Toru Noda, Kunihiko Akiyama.
  • Organizer: ARVO 2014 Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2014-05-04 – 2014-05-08
• [Presentation] Clinical and Genetic Characteristics of Childhood-onset Stargardt Disease (2014)
  • Author(s): Fujinami K, Zernant J, Ozawa Y, Tsubota K, Robson AG, Holder GE, Webster AR, Alikmets R, Michaelides M, Moore AT
  • Organizer: ARVO 2014 Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2014-05-04 – 2014-05-08
• [Presentation] The case of occult macular dystrophy which developed local retinal detachment at fovea with vitreous traction (2014)
  • Author(s): Kato Y, Fujinami K, Noda T, Akahori M, Iwata T, Miyake Y, Tsunoda K
  • Organizer: ARVO 2014 Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2014-05-04 – 2014-05-08
• [Presentation] Case report of Monocular rod-cone dystrophy, which suspected Melanoma associated retinopathy. (2014)
  • Author(s): Toshihiko Hirakata, Kaoru Fujinami, Kazunori Tsunoda, Akito Hirakata, Yozo Miyake
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology
  • Place of Presentation: Tokyo
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] Siblings with Childhood-Onset Stargardt Disease Associated with External Limiting Membrane Thickening (2014)
  • Author(s): Ikko Iehisa, Kaoru Fujinami, Natsuko Nakamura, Toru Noda, Kazushige Tsunoda
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology
  • Place of Presentation: Tokyo
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] Fundus Manifestations of Hereditary Hemorrhagic Telangiectasia (Rendu-Osler-Weber Disease). (2014)
  • Author(s): Kato Y, Fujinami K, Noda T, Miyake Y, Tsunoda K
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology
  • Place of Presentation: Tokyo
  • Year and Date: 2014-04-02 – 2014-04-06
• [Book] Fundus Autofluorescence (2014)
  • Author(s): Kazushige Tsunoda
  • Total Pages: 200
  • Publisher: Lippincott, Williams and Wilkins
• [Book] 眼科臨床クローズアップ (2014)
  • Author(s): 角田和繁
  • Total Pages: 250
  • Publisher: メジカルビュー社
• [Book] 眼科グラフィック (2014)
  • Author(s): 角田和繁
  • Total Pages: 300
  • Publisher: メディカ出版