New concept of electroretinography in photoreceptor degenerative diseases

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17K19721
• Research Institution: Mie University
• Principal Investigator: 近藤 峰生 三重大学, 医学系研究科, 教授 (80303642)
• Co-Investigator(Kenkyū-buntansha): 杉本 昌彦 三重大学, 医学部附属病院, 講師 (00422874) ; 生杉 謙吾 三重大学, 医学系研究科, 准教授 (10335135) ; 松原 央 三重大学, 医学部附属病院, 講師 (20378409)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 網膜電図 / ERG / ウサギ / a波 / 視細胞 / 網膜色素変性 / 動物モデル / 薬理学的実験

Outline of Annual Research Achievements

本年度は、網膜色素変性のモデルウサギであるP347L Tgウサギの進行期（生後２年）において、硝子体中にtetrodotoxin (TTX)とN-methyl-D-aspartic acid (NMDA)を作用させた後にERGを記録した。TTX とNMDA を同時に硝子体内に注射すると網膜の3 次ニューロン（アマクリン細胞および網膜神経節細胞）はほぼ完全に遮断される。TTX＋NMDA を作用させたあとに、進行した変性Tg ウサギのERG のa 波がどの程度低下するかを観察した。今回の研究の結果、P347L Tgウサギの進行期において、最大の光刺激でわずかに記録される陰性波は、TTX＋NMDA で完全に消失することがわかった。同様の実験は、さらに生後3 年のTg ウサギでも行い、同じ結果であることが確認された。以上の結果は、これまでのERGの概念を変える新しい所見であると考えられた。これまでのERG概念では、哺乳類のERGのa波は暗所で記録した場合は杆体視細胞の電位に由来し、一方で明所で記録した場合は錐体視細胞に加えて錐体OFF型双極細胞由来と考えられており、網膜の3次ニューロンの関与については全く知られていなかった。仮にそれがあったとしても、無視しうるほどに小さいと信じられてきた。しかしながら、末期の網膜色素変性のように視細胞が重度に変性した状態においては、わずかに記録される陰性波のa波（そのほとんどは錐体系a波）は3次ニューロン由来であった。これは眼科臨床において進行期の網膜色素変性患者から記録されるわずかなa波を残存視細胞機能と推定してはいけないことになり、眼科の臨床検査においても重要な意義を有する結果であると考えられた。

Research Products

• [Journal Article] Genetic Spectrum of EYS-associated Retinal Disease in a Large Japanese Cohort: Identification of Disease-associated Variants with Relatively High Allele Frequency (2020)
  • Author(s): 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; JEGC study group
  • Journal Title: Sci Rep Volume: 10 Pages: 5497
  • DOI: 10.1038/s41598-020-62119-3.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparisons of Effective Fields of Two Ultra-Widefield Ophthalmoscopes, Optos 200Tx and Clarus 500 (2019)
  • Author(s): Matsui Y, Ichio A, Sugawara A, Uchiyama E, Suimon H, Matsubara H, Sugimoto M, Ikesugi K, Kondo M
  • Journal Title: Biomed Res Int Volume: 2019 Pages: 7436293
  • DOI: 10.1155/2019/7436293.
  • Peer Reviewed / Open Access
• [Journal Article] Pathoconnectome Analysis of Muller Cells in Early Retinal Remodeling (2019)
  • Author(s): Pfeiffer RL, Anderson JR, Emrich DP, Dahal J, Sigulinsky CL, Morrison HAB, Yang JH, Watt CB, Rapp KD, Kondo M, Terasaki H, Garcia JC, Marc RE, Jones BW
  • Journal Title: Adv Exp Med Biol Volume: 1185 Pages: 365-370
  • DOI: doi: 10.1007/978-3-030-27378-1_60.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intraocular pressure elevation after subtenon triamcinolone acetonide injection; Multicentre retrospective cohort study in Japan (2019)
  • Author(s): Maeda Y, Ishikawa H, Nishikawa H, Shimizu M, Kinoshita T, Ogihara R, Kitano S, Yamanaka C, Mitamura Y, Sugimoto M, Kondo M, Takamura Y, Ogata N, Ikeda T, Gomi F
  • Journal Title: PLoS One Volume: 14 Pages: e0226118
  • DOI: 10.1371/journal.pone.0226118.
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between Size of the Foveal Avascular Zone and Carbohydrate Metabolic Disorders during Pregnancy (2019)
  • Author(s): Sugimoto M, Wakamatsu Y, Miyata R, Matsubara H, Kondo M, Kamimoto Y, Ikeda T
  • Journal Title: Biomed Res Int Volume: 2019 Pages: 3261279
  • DOI: 10.1155/2019/3261279.
  • Peer Reviewed / Open Access
• [Journal Article] ISCEV extended protocol for the S-cone ERG (2019)
  • Author(s): Perlman I, Kondo M, Chelva E, Robson AG, Holder GE
  • Journal Title: Doc Ophthalmol Volume: 140 Pages: 95-101
  • DOI: 10.1007/s10633-019-09730-6. Epub 2019 Nov 20.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of GUCA1A-associated dominant cone/cone-rod dystrophy: low prevalence among Japanese patients with inherited retinal dystrophies (2019)
  • Author(s): Mizobuchi K, Hayashi T, Katagiri S, Yoshitake K, Fujinami K, Yang L, Kuniyoshi K, Shinoda K, Machida S, Kondo M, Ueno S, Terasaki H, Matsuura T, Tsunoda K, Iwata T, Nakano T
  • Journal Title: Sci Rep Volume: 9 Pages: 16851
  • DOI: 10.1038/s41598-019-52660-1.
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Stages of Occult Macular Dystrophy Based on Optical Coherence Tomographic Findings (2019)
  • Author(s): Nakamura N, Tsunoda K, Mizuno Y, Usui T, Hatase T, Ueno S, Kuniyoshi K, Hayashi T, Katagiri S, Kondo M, Kameya S, Yoshitake K, Fujinami K, Iwata T, Miyake Y
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 60 Pages: 4691-4700
  • DOI: 10.1167/iovs.19-27486.
  • Peer Reviewed
• [Journal Article] Refractive error and biometrics of anterior segment of eyes of healthy young university students in Japan (2019)
  • Author(s): Kato K, Kondo M, Takeuchi M, Hirano K
  • Journal Title: Sci Rep Volume: 9 Pages: 15337
  • DOI: 10.1038/s41598-019-51920-4.
  • Peer Reviewed / Open Access
• [Journal Article] Risk Factors of Neovascular Glaucoma After 25-gauge Vitrectomy for Proliferative Diabetic Retinopathy with Vitreous Hemorrhage: A Retrospective Multicenter Study (2019)
  • Author(s): Takayama K, Someya H, Yokoyama H, Takamura Y, Morioka M, Sameshima S, Ueda T, Kitano S, Tashiro M, Sugimoto M, Kondo M, Sakamoto T, Takeuchi M
  • Journal Title: Sci Rep Volume: 9 Pages: 14858
  • DOI: 10.1038/s41598-019-51411-6.
  • Peer Reviewed / Open Access
• [Journal Article] Coexistence of GNAT1 and ABCA4 variants associated with Nougaret-type congenital stationary night blindness and childhood-onset cone-rod dystrophy (2019)
  • Author(s): Hayashi T, Hosono K, Kurata K, Katagiri S, Mizobuchi K, Ueno S, Kondo M, Nakano T, Hotta Y
  • Journal Title: Doc Ophthalmol Volume: 140 Pages: 147-157
  • DOI: 10.1007/s10633-019-09727-1.
  • Peer Reviewed
• [Journal Article] Genome-wide association study and whole-genome sequencing identify a deletion in LRIT3 associated with canine congenital stationary night blindness. (2019)
  • Author(s): Das RG, Becker D, Jagannathan V, Goldstein O, Santana E, Carlin K, Sudharsan R, Leeb T, Nishizawa Y, Kondo M, Aguirre GD, Miyadera K.
  • Journal Title: Sci Rep Volume: 9 Pages: 14166
  • DOI: 10.1038/s41598-019-50573-7.
  • Peer Reviewed / Open Access
• [Journal Article] Management of Postoperative Inflammation and Dry Eye After Cataract Surgery. (2019)
  • Author(s): Kato K, Miyake K, Hirano K, Kondo M
  • Journal Title: Cornea Volume: 38 Suppl Pages: S25-S33
  • DOI: 10.1097/ICO.0000000000002125.
  • Peer Reviewed
• [Journal Article] Expression of vascular infarction-related molecules after anti-vascular endothelium growth factor treatment for diabetic macular edema (2019)
  • Author(s): Sugimoto M, Wakamatsu Y, Miyata R, Nunome T, Tenma Y, Matsubara H, Kondo M, Wada H, Nakatani K
  • Journal Title: Sci Rep Volume: 9 Pages: 12373
  • DOI: 10.1038/s41598-019-48869-9.
  • Peer Reviewed / Open Access
• [Journal Article] Current practice in the management of branch retinal vein occlusion in Japan: Survey results of retina specialists in Japan. (2019)
  • Author(s): Ogura Y, Kondo M, Kadonosono K, Shimura M, Kamei M, Tsujikawa A
  • Journal Title: Jpn J Ophthalmol Volume: 63 Pages: 365-373
  • DOI: 10.1007/s10384-019-00685-4.
• [Journal Article] Changes in VEGF-related factors are associated with presence of inflammatory factors in carbohydrate metabolism disorders during pregnancy (2019)
  • Author(s): Sugimoto M, Kondo M, Kamimoto Y, Ikeda T, Cutler A, Mariya A, Anand-Apte B
  • Journal Title: PLoS One Volume: 14 Pages: e0220650
  • DOI: 10.1371/journal.pone.0220650.
  • Peer Reviewed / Open Access
• [Journal Article] Electrically Evoked Potentials Are Reduced Compared to Axon Numbers in Rhodopsin P347L Transgenic Rabbits With Severe Photoreceptor Degeneration. (2019)
  • Author(s): Kominami T, Ueno S, Nishida K, Inooka D, Kominami A, Kondo M, Terasaki H.
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 60 Pages: 2543-2550
  • DOI: 10.1167/iovs.19-26972.
  • Peer Reviewed
• [Journal Article] Tilted Disc Syndrome Associated with Serous Retinal Detachment: Long-term Prognosis. A Retrospective Multicenter Survey. (2019)
  • Author(s): Kubota F, Suetsugu T, Kato A, Gomi F, Takagi S, Kinoshita T, Ishikawa H, Mitamura Y, Kondo M, Iwahashi C, Kuwayama S, Kurimoto Y, Ogura Y, Yasukawa T; Japanese Clinical Retina Study (J-CREST) Group.
  • Journal Title: Am J Ophthalmol Volume: 207 Pages: 313-318
  • DOI: 10.1016/j.ajo.2019.05.027.
  • Peer Reviewed
• [Journal Article] Course of loss of photoreceptor function and progressive Muller cell gliosis in rhodopsin P347L transgenic rabbits (2019)
  • Author(s): Ueno S, Kominami T, Okado S, Inooka D, Kondo M, Terasaki H.
  • Journal Title: Exp Eye Res Volume: 207 Pages: 192-200
  • DOI: 10.1016/j.exer.2019.04.026.
  • Peer Reviewed
• [Journal Article] Clinical and Genetic Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake Disease): East Asia Occult Macular Dystrophy Studies Report Number 1 (2019)
  • Author(s): Fujinami K, Yang L, Joo K, Tsunoda K, Kameya S, Hanazono G, Fujinami-Yokokawa Y, Arno G, Kondo M, Nakamura N, Kurihara T, Tsubota K, Zou X, Li H, Park KH, Iwata T, Miyake Y, Woo SJ, Sui R; East Asia Inherited Retinal Disease Society study group
  • Journal Title: Ophthalmology Volume: 126 Pages: 1432-1444.
  • DOI: 10.1016/j.ophtha.2019.04.032.
  • Peer Reviewed
• [Journal Article] ISCEV extended protocol for the stimulus-response series for light-adapted full-field ERG (2019)
  • Author(s): McCulloch DL, Kondo M, Hamilton R, Lachapelle P, Messias AMV, Robson AG, Ueno S.
  • Journal Title: Doc Ophthalmol Volume: 138 Pages: 205-215
  • DOI: 10.1007/s10633-019-09685-8.
  • Peer Reviewed / Open Access
• [Journal Article] Central serous chorioretinopathy with and without steroids: A multicenter survey (2019)
  • Author(s): Araki T, Ishikawa H, Iwahashi C, Niki M, Mitamura Y, Sugimoto M, Kondo M, Kinoshita T, Nishi T, Ueda T, Kato A, Yasukawa T, Takamura Y, Gomi F.
  • Journal Title: PLoS One Volume: 14 Pages: e0213110
  • DOI: 10.1371/journal.pone.0213110.
  • Peer Reviewed / Open Access
• [Journal Article] Novel mutations in the RS1 gene in Japanese patients with X-linked congenital retinoschisis. (2019)
  • Author(s): Kondo H, Oku K, Katagiri S, Hayashi T, Nakano T, Iwata A, Kuniyoshi K, Kusaka S, Hiyoshi A, Uchio E, Kondo M, Oishi N, Kameya S, Mizota A, Naoi N, Ueno S, Terasaki H, Morimoto T, Iwaki M, Yoshitake K, Iejima D, Fujinami K, Tsunoda K, Shinoda K, Iwata T.
  • Journal Title: Hum Genome Var Volume: 8 Pages: 3
  • DOI: 10.1038/s41439-018-0034-6.
  • Peer Reviewed / Open Access
• [Presentation] Clinical applications of the mfERG (2019)
  • Author(s): Kondo M
  • Organizer: 57th ISCEV SYMPOSIUM
  • Int'l Joint Research / Invited
• [Presentation] A clinical diagnostic approach to retinal disease. (2019)
  • Author(s): Kondo M
  • Organizer: 57th ISCEV SYMPOSIUM
  • Int'l Joint Research / Invited
• [Presentation] ISCEV Instruction Course: Clinical Usefulness of Electrophysiology. (2019)
  • Author(s): Kondo M
  • Organizer: APAO
  • Int'l Joint Research
• [Presentation] Supernormal Flicker ERGs in Eyes with Central Retinal Vein Occlusion: Clinical Characteristics, Prognosis, and Effects of Anti-VEGF Agent. (2019)
  • Author(s): Kondo M
  • Organizer: 42nd ANNUAL MEETING MACULA SOCIETY
  • Int'l Joint Research