Study on molecular mechanism causing autoimmune retinopathy

• Project/Area Number: 25462723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Sapporo Medical University
• Principal Investigator: Hiroshi Ohguro 札幌医科大学, 医学部, 教授 (30203748)
• Co-Investigator(Kenkyū-buntansha): 阿部 晃 札幌医科大学, 医学部, 講師 (70136927) ; 平岡 美紀 札幌医科大学, 医学部, 講師 (80246983)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 網膜 / 自己免疫性網膜症 / リカバリン / 腫瘍随伴神経症 / 癌関連網膜症 / 自己免疫 / 自己免疫網膜症 / TRPM1 / molecul;ar mimicry / recoverin

Outline of Final Research Achievements

To elucidate the molecular pathology in autoimmune retinopathy (AIR), regulatory mechanism of expressions of autoantigen causing AIR as well as what kinds of role of such autoantigen aberrantly expressed in malignant tumor cells or none tumor cells were examined. Recoverin was identified to be expressed in 30-70% of cancer tissues. We observed co-precipitation of G-protein-coupled-kinases (GRKs) and caveolin-1 with Rec from cell lysates of 293 or SSTW cells. Immunocytechemistry revealed that immunoreactivities toward recoverin within the cancer cells were almost identical to those toward GRKs and caveolin-1. The present data strongly suggests that aberrantly expressed recoverin should be involved in the GRK-dependent cellular regulation in cancer cells.

Research Products

• [Journal Article] Prolonged Ocular Inflammation in Endotoxin-Induced Uveitis in Lysosomal Phospholipase A2-Deficient Mice. (2017)
  • Author(s): Sawada K, Hiraoka M, Abe A, Kelly R, Shayman JA, Ohguro H.
  • Journal Title: Curr Eye Res. Volume: ４２ Issue: 4 Pages: 611-616
  • DOI: 10.1080/02713683.2016.1214967
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Acute Bilateral Photoreceptor Degeneration in an Infant After Vaccination Against Measles and Rubella. (2017)
  • Author(s): Kuniyoshi K, Hatsukawai Y, Kimura S, Fujino T, Ohguro H, Nakai R, Sunami K, Mishima SI, Sato T, Kusaka S, Suzuki Y, Shimomura Y.
  • Journal Title: JAMA Ophthalmol. Volume: 印刷中 Issue: 5 Pages: 478-482
  • DOI: 10.1001/jamaophthalmol.2017.0380
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2. (2017)
  • Author(s): Abe A, Hiraoka M, Ohguro H, Tesmer JJ, Shayman JA.
  • Journal Title: J Lipid Res. Volume: ５８ Issue: 2 Pages: 339-349
  • DOI: 10.1194/jlr.m070730
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Acute Retinal Necrosis Associated with Epstein-Barr Virus in a Patient Undergoing Immunosuppressive Therapy. (2016)
  • Author(s): Oe C, Hiraoka M, Tanaka S, Ohguro H.
  • Journal Title: Case Rep Ophthalmol. Volume: １２ Issue: 1 Pages: 195-201
  • DOI: 10.1159/000445372
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fluctuation of lysosomal phospholipase A2 in experimental autoimmune uveitis in rats. (2016)
  • Author(s): Ohkawa E, Hiraoka M, Abe A, Murata M, Ohguro H.
  • Journal Title: Exp Eye Res. Volume: １４９ Pages: 66-74
  • DOI: 10.1016/j.exer.2016.06.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of Antiglaucoma Medicine on Intraocular Pressure in DBA/2J Mice. (2016)
  • Author(s): Sawada K, Hiraoka M, Ohguro H.
  • Journal Title: Ophthalmic Research Volume: 55 Issue: 4 Pages: 205-211
  • DOI: 10.1159/000444057
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The signal intensity ratio of the optic nerve to ipsilateral frontal white matter is of value in the diagnosis of acute optic neuritis. (2016)
  • Author(s): Onodera M, Yama N, Hashimoto M, Shonai T, Aratani K, Takashima H, Kamo K, Nagahama H, Ohguro H, Hatakenaka M.
  • Journal Title: Eur Radiol. Volume: ２６ Issue: 8 Pages: 2640-2645
  • DOI: 10.1007/s00330-015-4114-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Augmentation of Lysosomal Phospholipase A2 Activity in the Anterior Chamber in Glaucoma. (2015)
  • Author(s): Hiraoka M, Abe A, Inatomi S, Sawada K, Ohguro H.
  • Journal Title: Current Eye Research Volume: 19 Issue: 5 Pages: 1-6
  • DOI: 10.3109/02713683.2015.1056800
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Increase of lysosomal phospholipase A2 in aqueous humor by uveitis. (2014)
  • Author(s): Hiraoka M, Abe A, Lennikov A, Kitaichi N, Ishida S, Ohguro H
  • Journal Title: Exp Eye Res Volume: 118. Pages: 13-19
  • DOI: 10.1016/j.exer.2013.09.018
  • Peer Reviewed
• [Journal Article] Effects of several anti-glaucoma medications on the circadian intraocular pressure fluctuations in patients with primary open-angle glaucoma. (2014)
  • Author(s): Tanaka S, Watanabe M, Inatomi S, Umeda K, Yoshida K, Ohguro I, Ohguro H
  • Journal Title: Journal of Ocular Pharmacology and Therapeutics Volume: 30 Issue: 1 Pages: 12-20
  • DOI: 10.1089/jop.2013.0121
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] IkappaB kinase-β inhibitor IMD-0354 beneficially suppresses retinal vascular permeability in streptozotocin-induced diabetic mice. (2014)
  • Author(s): Lennikov A, Hiraoka M, Abe A, Ohno S, Fujikawa T, Itai A, Ohguro H
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 55 Issue: 10 Pages: 6365-6373
  • DOI: 10.1167/iovs.14-14671
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of cryptogenic onganizing pneumonia in bilateral anterior uveitis. (2014)
  • Author(s): Fujimoto K, Hiraoka M, Inatomi S, Ohguro H
  • Journal Title: Case Rep Ophthalmol Volume: 5 Issue: 3 Pages: 365-372
  • DOI: 10.1159/000369125
  • Peer Reviewed
• [Journal Article] Recoverin-associated retinopathy secondary to Warthin tumor of parotid gland. (2014)
  • Author(s): Machida S, Ohguro H, Ishida K, Suzuki M, Kawagishi K.
  • Journal Title: Doc Ophthalmol Volume: 129 Issue: 2 Pages: 123-128
  • DOI: 10.1007/s10633-014-9456-8
  • Peer Reviewed
• [Journal Article] A case of paraneoplastic optic neuropathy and outer retinitis positive for autoantibodies against collapsin response mediator protein-5, recoverin, and α-enolase. (2014)
  • Author(s): Saito M, Saito W, Kanda A, Ohguro H, Ishida S.
  • Journal Title: BMC Ophthalmol. Volume: 14 Issue: 1 Pages: 5-5
  • DOI: 10.1186/1471-2415-14-5
  • Peer Reviewed
• [Journal Article] Site-dependent differences in density of sympathetic nerve fibers in muscle-innervating nerves of the human head and neck. (2014)
  • Author(s): Hosaka F, Katori Y, Kawase T, Fujimiya M, Ohguro H.
  • Journal Title: Anat Sci Int. Volume: 89 Pages: 101-111
  • Peer Reviewed
• [Journal Article] Effects of black currant anthocyanins on intraocular pressure in healthy volunteers and patients with glaucoma. (2013)
  • Author(s): Ohguro H, Ohguro I, Yagi S
  • Journal Title: Journal of Ocular Pharmacology and Therapeutics Volume: 29(1) Issue: 1 Pages: 61-67
  • DOI: 10.1089/jop.2012.0071
  • Peer Reviewed
• [Journal Article] Qualitative changes in fetal trabecular meshwork fibers at the human iridocorneal angle. (2013)
  • Author(s): Hosaka F, Rodríguez-Vázquez JF, Abe H, Murakami G, Fujimiya M, Ohguro H
  • Journal Title: Anat Cell Biol Volume: 46(1) Issue: 1 Pages: 49-56
  • DOI: 10.5115/acb.2013.46.1.49
  • Peer Reviewed
• [Journal Article] Black currant anthocyanins normalized abnormal levels of serum concentrations of endothelin-1 in patients with glaucoma. (2013)
  • Author(s): Yoshida K, Ohguro I, Ohguro H
  • Journal Title: Journal of Ocular Pharmacology and Therapeutics Volume: 29(5) Issue: 5 Pages: 480-487
  • DOI: 10.1089/jop.2012.0198
  • Peer Reviewed
• [Journal Article] Role of N-glycosylation of human lysosomal phospholipase A2 for the formation of catalytically active enzyme. (2013)
  • Author(s): Hiraoka M, Okamoto K, Ohguro H, Abe A
  • Journal Title: J Lipid Res Volume: 54 Issue: 11 Pages: 3098-3105
  • DOI: 10.1194/jlr.m041640
  • Peer Reviewed
• [Presentation] Instruction in basic techniques for cataract surgery using simulated models and diagrams. (2014)
  • Author(s): Hosaka F, Takemori T, Ohguro H
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo Forum Ｔｏｋｙｏ， Ｊａｐａｎ
  • Year and Date: 2014-04-02 – 2014-04-04
• [Presentation] The involvement of lysosomal phospholipase A2 in glaucoma. (2014)
  • Author(s): Hiraoka M, Abe A, Inatomi S, Sawada K, Ohguro H
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo Forum Ｔｏｋｙｏ， Ｊａｐａｎ
  • Year and Date: 2014-04-02 – 2014-04-04
• [Presentation] Cancer-associated retinopathy in a child with Langerhans cell histiocytosis. (2014)
  • Author(s): Hatsukawa Y, Hayashi M, Yasui M, Ohguro H
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo Forum Ｔｏｋｙｏ， Ｊａｐａｎ
  • Year and Date: 2014-04-02 – 2014-04-04
• [Presentation] Case report of cancer-associated retinopathy with rapid onset severe visual loss. (2014)
  • Author(s): Murakami T, Namba H, Tomita Y, Ohguro H, Yamashita H
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo Forum Ｔｏｋｙｏ， Ｊａｐａｎ
  • Year and Date: 2014-04-02 – 2014-04-04
• [Presentation] Involvement of lysosomal phospholipase A2 in endotoxin-induced uveitis mice. (2014)
  • Author(s): Sawada K, Abe A, Hiraoka M, Lennikov A, Ohguro H
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo Forum Ｔｏｋｙｏ， Ｊａｐａｎ
  • Year and Date: 2014-04-02 – 2014-04-04
• [Presentation] The role of lysosomal phospholipase A2 in the experimental autoimmune uveitis model of rats. (2014)
  • Author(s): Ohkawa E, Lennikov A, Hiraoka M, Abe A, Ohguro H
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo Forum Ｔｏｋｙｏ， Ｊａｐａｎ
  • Year and Date: 2014-04-02 – 2014-04-04
• [Presentation] Protective effect of yellow filter on light-induced retinal damage in rats. (2014)
  • Author(s): Hikage F, Lennikov A, Hiraoka M, Abe A, Ohguro H
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo Forum Ｔｏｋｙｏ， Ｊａｐａｎ
  • Year and Date: 2014-04-02
• [Presentation] Connective tissue growth factor as a pathogen of proliferation of the retina in spontaneously diabetic torii rat. (2013)
  • Author(s): Maeda K, Ohguro I, Hiraoka M, Abe A, Ohguro H
  • Organizer: The 8th APVRS Congress & The 52nd Annual meeting of Japanese Retina and Vitreous Society
  • Place of Presentation: Nagoy, Japan
• [Presentation] The lysosomal phospholipase A2 activity in aqueous humor of patients with retinal diseases. (2013)
  • Author(s): Sugawara A, Hiraoka M, Abe A, Ishikawa F, Ohguro H
  • Organizer: The 8th APVRS Congress & The 52nd Annual meeting of Japanese Retina and Vitreous Society
  • Place of Presentation: Nagoy, Japan
• [Presentation] Low levels of plasma endothelin-1（ET-1）in patients with retinitis pigmentosa. (2013)
  • Author(s): Ohguro H, Nakazawa M
  • Organizer: The 8th APVRS Congress & The 52nd Annual meeting of Japanese Retina and Vitreous Society
  • Place of Presentation: Nagoy, Japan
• [Presentation] A rare case of familial exudative vitreoretinopathy (FEVR) with Kabuki Make-Up Sydrome. (2013)
  • Author(s): Yoshida K, Watanabe M, Hikage F, Sugawara A, Ishikawa F, Ohguro H
  • Organizer: The 8th APVRS Congress & The 52nd Annual meeting of Japanese Retina and Vitreous Society
  • Place of Presentation: Nagoy, Japan
• [Presentation] Clinicopathological roles of aberrantly expressed recoverin in malignant tumor cells. (2013)
  • Author(s): Watanabe M, Matsuo S, Ohguro I, Ohguro H
  • Organizer: The 8th APVRS Congress & The 52nd Annual meeting of Japanese Retina and Vitreous Society
  • Place of Presentation: Nagoy, Japan
• [Book] 第9章 視神経.「標準眼科学 第12版（木下 茂・中澤 満・天野史郎 編集）」 (2013)
  • Author(s): 大黒 浩
  • Total Pages: 403
  • Publisher: 医学書院
• [Book] Glaucoma 私のArchives房水循環のなぞ.「Frontiers in Glaucoma 第45号」 (2013)
  • Author(s): 大黒 浩
  • Total Pages: 88
  • Publisher: メディカルレビュー社
• [Book] IV その他の疾患 ④神経眼科疾患6視神経管骨折. 「眼科疾患最新の治療2013-2015（大橋裕一・白神史雄 編集）」 (2013)
  • Author(s): 大黒 浩
  • Total Pages: 376
  • Publisher: 南江堂
• [Book] 1.検査と診察 サイエンテイフィック・クエスチョン 網膜が剥離すると視物質はどうなるのでしょうか？「専門医のための眼科診療クオリファイ⑰裂孔原性網膜剥離-How to treat（瓶井資弘編集）」 (2013)
  • Author(s): 大黒 浩
  • Total Pages: 386
  • Publisher: 中山書店