加齢黄斑変性に対するテーラーメード医療の実現

2011 年度 研究成果報告書

• 研究課題/領域番号: 21249084
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 眼科学
• 研究機関: 京都大学
• 研究代表者: 吉村 長久 京都大学, 医学研究科, 教授 (70211662)
• 研究分担者: 大谷 篤史 京都大学, 医学研究科, 講師 (30314222) ; 山城 健児 京都大学, 医学研究科, 助教 (80399617) ; 山田 亮 京都大学, 医学研究科, 教授 (50301106)
• 研究期間 (年度): 2009 – 2011
• キーワード: 眼細胞生物学

研究概要

ARMS2遺伝子A69Sの迅速検出キットを作成した。A69S多型は滲出型加齢黄斑変性に対する光線力学療法後の視力予後に相関し、抗VEGF治療の後の視力予後には相関しなかったことから、このキットを用いることによって、個別化医療が実現できると考えられた。さらに他の候補として、VEGF遺伝子、PEDF遺伝子が治療後反応を予測し、精度の高い個別化医療の実現が可能であることが分かった。

研究成果

• [雑誌論文] Significance ofC2/CFB variants in age-related macular degeneration and polypoidal choroidalvasculopathy in a Japanese population (2012)
  • 著者名/発表者名: Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanishi H, Hayashi H, Akagi-Kurashige Y, Tsujikawa A, Otani A, Saito M, Iida T, Oishi A, Matsuo K, TajimaK, Matsuda F, Yoshimura N.
  • 雑誌名: Invest Ophthalmol Vis Sci 巻: 53 ページ: 794-8
• [雑誌論文] Macular Choroidal Thickness and Volume in Eyes With Angioid Streaks Measured by Swept Source Optical Coherence Tomography (2012)
  • 著者名/発表者名: Ellabban AA, Tsujikawa A, Matsumoto A, Ogino K, Hangai M, Ooto S, Yamashiro K, Akiba M, Yoshimura N.
  • 雑誌名: Am JOphthalmol
• [雑誌論文] Relationship between retinal morphological findings and visual function in age-related macular degeneration (2012)
  • 著者名/発表者名: Akagi-Kurashige Y, Tsujikawa A, Oishi A, Ooto S, Yamashiro K, Tamura H, Nakata I, Ueda-Arakawa N, Yoshimura N.
  • 雑誌名: Graefes Arch Clin Exp Ophthalmol
• [雑誌論文] Vascular endothelial growth factor gene polymorphisms and choroidalneovascularization in highly myopic eyes (2012)
  • 著者名/発表者名: Akagi-Kurashige Y, Kumagai K, Yamashiro K, Nakanishi H, Nakata I, MiyakeM, Tsujikawa A, Moriyama M, Ohno-Matsui K, Mochizuki M, Yamada R, Matsuda F, Yoshimura N
  • 雑誌名: Invest Ophthalmol Vis Sci
• [雑誌論文] Association of elastin gene polymorphism to age-related macular degeneration and polypoidal choroidalvasculopathy (2011)
  • 著者名/発表者名: Yamashiro K, Mori K, Nakata I, Tsuchihashi T, Horie-Inoue K, Nakanishi H, Tsujikawa A, Saito M, Iida T, Yamada R, Matsuda F, Inoue S, Awata T, Yoneya S, Yoshimura N
  • 雑誌名: Invest Ophthalmol Vis Sci 巻: 52 ページ: 8780-4
• [雑誌論文] Development of polypoidal lesions inage-related macular degeneration (2011)
  • 著者名/発表者名: Tsujikawa A, Ojima Y, Yamashiro K, Ooto S, Tamura H, Nakata I, Yoshimura N
  • 雑誌名: Eye 巻: 25 ページ: 481-8
• [雑誌論文] Association of lesion size and visual prognosis to polypoidal choroidalvasculopathy (2011)
  • 著者名/発表者名: Tsujikawa A, Ojima Y, Yamashiro K, Nakata I, Ooto S, Tamura H, Nakanishi H, Hayashi H, Otani A, Yoshimura N
  • 雑誌名: Am J Ophthalmol 巻: 151 ページ: 961-972
• [雑誌論文] Retinal micro structural abnormalities in central serous chorioretinopathy andpolypoidal choroidal vasculopathy (2011)
  • 著者名/発表者名: Ooto S, Tsujikawa A, Mori S, Tamura H, Yamashiro K, Otani A, Yoshimura N
  • 雑誌名: Retina 巻: 31 ページ: 527-34
• [雑誌論文] Association between the SERPING1 gene andage-related macular degeneration andpolypoidal choroidal vasculopathy in Japanese (2011)
  • 著者名/発表者名: Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanishi H, Hayashi H, TsujikawaA, Otani A, Saito M, Iida T, Oishi A, MatsuoK, Tajima K, Matsuda F, Yoshimura N
  • 雑誌名: PLoS One 巻: 6 ページ: 19108
• [雑誌論文] Genetic variants in pigment epithelium-derived factor influence response of polypoidal choroidalvasculopathy to photodynamic therapy (2011)
  • 著者名/発表者名: Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanishi H, Hayashi H, TsujikawaA, Otani A, Ooto S, Tamura H, Saito M, SaitoK, Iida T, Oishi A, Kurimoto Y, Matsuda F, Yoshimura N.
  • 雑誌名: Ophthalmology 巻: 118 ページ: 1408-15
• [雑誌論文] VEGFgene polymorphism and response tointravitreal bevacizumab and triple therapy in age-related macular degeneration (2011)
  • 著者名/発表者名: Nakata I, Yamashiro K, NakanishiH, Tsujikawa A, Otani A, Yoshimura N.
  • 雑誌名: Jpn J Ophthalmol 巻: 55 ページ: 435-43
• [雑誌論文] Prognostic factors for visual outcomes 2-years afterintravitreal bevacizumab for myopicchoroidal neovascularization (2011)
  • 著者名/発表者名: Nakanishi H, Tsujikawa A, Yodoi Y, Ojima Y, Otani A, Tamura H, Yamashiro K, Ooto S, Yoshimura N.
  • 雑誌名: Eye 巻: 25 ページ: 375-81
• [雑誌論文] Macular choroidal thickness and volume in normal subjects measured by swept-source optical coherence tomography (2011)
  • 著者名/発表者名: Hirata M, Tsujikawa A, MatsumotoA, Hangai M, Ooto S, Yamashiro K, Akiba M, Yoshimura N.
  • 雑誌名: Invest Ophthalmol Vis Sci 巻: 52 ページ: 4971-8
• [雑誌論文] Association of 15q14 and 15q25 with high myopia in Japanese (2011)
  • 著者名/発表者名: Hayashi H, Yamashiro K, NakanishiH, Nakata I, Kurashige Y, Tsujikawa A, Moriyama M, Ohno-Matsui K, Mochizuki M, Ozaki M, Yamada R, Matsuda F, Yoshimura N.
  • 雑誌名: Invest Ophthalmol VisSci 巻: 52 ページ: 4853-8
• [雑誌論文] Sterile endophthalmitis afterintravitreal injection of bevacizumabobtained from a single batch (2010)
  • 著者名/発表者名: Yamashiro K, Tsujikawa A, Miyamoto K, Oh H, Otani A, Tamuara H, Ooto S, Sasahara M, Iwama D, Yoshimura N.
  • 雑誌名: Retina 巻: 30 ページ: 485-90
• [雑誌論文] Treatment of polypoidal choroidal vasculopathy byintravitreal injection of bevacizumab (2010)
  • 著者名/発表者名: Tsujikawa A, Ooto S, Yamashiro K, Tamura H, Otani A, Yoshimura N.
  • 雑誌名: Jpn J Ophthalmol 巻: 54 ページ: 310-9
• [雑誌論文] Punctate hyper fluorescent spots associated with central serouschorioretinopathy as seen on indocyaninegreen angiography (2010)
  • 著者名/発表者名: Tsujikawa A, Ojima Y, Yamashiro K, Ooto S, Tamura H, Nakagawa S, Yoshimura N.
  • 雑誌名: Retina 巻: 30 ページ: 801-9
• [雑誌論文] Intravitreal bevacizumab for type 1 idiopathic macular telangiectasia (2010)
  • 著者名/発表者名: Takayama K, Ooto S, Tamura H, Yamashiro K, Otani A, Tsujikawa A, Yoshimura N.
  • 雑誌名: Eye 巻: 24 ページ: 1492-7
• [雑誌論文] Thickness of photoreceptor layers inpolypoidal choroidal vasculopathy and central serous chorioretinopathy (2010)
  • 著者名/発表者名: Ooto S, Tsujikawa A, Mori S, Tamura H, Yamashiro K, Yoshimura N.
  • 雑誌名: Graefes Arch Clin Exp Ophthalmol 巻: 248 ページ: 1077-86
• [雑誌論文] High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laserophthalmoscopy (2010)
  • 著者名/発表者名: Ooto S, Hangai M, Sakamoto A, Tsujikawa A, Yamashiro K, Ojima Y, Yamada Y, Mukai H, Oshima S, Inoue T, Yoshimura N
  • 雑誌名: Ophthalmology 巻: 117 ページ: 1800-9, 1809-2
• [雑誌論文] Restoration of outer segments of foveal photoreceptors after resolution of central serouschorioretinopathy (2010)
  • 著者名/発表者名: Ojima Y, Tsujikawa A, Yamashiro K, Ooto S, Tamura H, Yoshimura N
  • 雑誌名: Jpn J Ophthalmol. 巻: 54 ページ: 55-60
• [雑誌論文] Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms onpolypoidal choroidal vasculopathy (2010)
  • 著者名/発表者名: Nakanishi H, Yamashiro K, Yamada R, Gotoh N, Hayashi H, Nakata I, Saito M, Iida T, Oishi A, Kurimoto Y, Matsuo K, Tajima K, Matsuda F, Yoshimura N
  • 雑誌名: Invest Ophthalmol Vis Sci 巻: 51 ページ: 6183-7
• [雑誌論文] Single-nucleotide polymorphisms in the promoter region of matrixmetalloproteinase-1,-2, and-3 in Japanese with high myopia (2010)
  • 著者名/発表者名: Nakanishi H, Hayashi H, Yamada R, Yamashiro K, Nakata I, Shimada N, Ohno-Matsui K, Mochizuki M, Ozaki M, Yoshitake S, Kuriyama S, Saito M, Iida T, Matsuo K, Matsuda F, Yoshimura N
  • 雑誌名: Invest Ophthalmol Vis Sci 巻: 51 ページ: 4432-6
• [雑誌論文] ARMS2/HTRA1 and CFH polymorphisms are not associated withchoroidal neovascularization in highly myopic eyes of the elderly Japanese population (2010)
  • 著者名/発表者名: Nakanishi H, Gotoh N, Yamada R, Yamashiro K, Otani A, Hayashi H, TsujikawaA, Shimada N, Ohno-Matsui K, Mochizuki M, Saito M, Saito K, Iida T, Matsuda F, Yoshimura N.
  • 雑誌名: Eye 巻: 24 ページ: 1078-84
• [雑誌論文] Relationship between retinal sensitivity and morphologic changes in eyes with confluent soft drusen (2010)
  • 著者名/発表者名: Iwama D, Tsujikawa A, Ojima Y, Nakanishi H, Yamashiro K, Tamura H, OotoS, Yoshimura N
  • 雑誌名: Clin Experiment Ophthalmol 巻: 38 ページ: 483-8
• [雑誌論文] Macular hole formation following photodynamic therapy combined with intravitreal injection ofbevacizumab and triamcinolone acetonide (2010)
  • 著者名/発表者名: Iwama D, Ooto S, Tsujikawa A, Yamashiro K, Yoshimura N.
  • 雑誌名: Jpn J Ophthalmol 巻: 54 ページ: 364-6
• [雑誌論文] CFH and ARMS2variations in age-related macular degeneration, polypoidal choroidalvasculopathy, and retinal angiomatous proliferation (2010)
  • 著者名/発表者名: Hayashi H, Yamashiro K, Gotoh N, Nakanishi H, Nakata I, Tsujikawa A, OtaniA, Saito M, Iida T, Matsuo K, Tajima K, Yamada R, Yoshimura N.
  • 雑誌名: Invest Ophthalmol Vis Sci 巻: 51 ページ: 5914-9
• [雑誌論文] Prognostic factors of vitreous hemorrhage secondary to exudative age-related macular degeneration (2010)
  • 著者名/発表者名: Hasegawa T, Otani A, Sasahara M, Gotoh N, Ooto S, Tamura H, Yamashiro K, Tsujikawa A, Yoshimura N.
  • 雑誌名: Am J Ophthalmol 巻: 149 ページ: 322-329
• [雑誌論文] Haplotypeanalysis of the ARMS2/HTRA1 region in Japanese patients with typicalneovascular age-related macular degeneration or polypoidal choroidal vasculopathy (2010)
  • 著者名/発表者名: Gotoh N, Yamashiro K, Nakanishi H, Saito M, Iida T, Yoshimura N
  • 雑誌名: Jpn J Ophthalmol 巻: 54 ページ: 609-14
• [雑誌論文] Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration (2010)
  • 著者名/発表者名: Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, Tosakulwong N, Pericak-Vance MA, Campochiaro PA, Klein ML, Tan PL, ConleyYP, Kanda A, Kopplin L, Li Y, AugustaitisKJ, Karoukis AJ, Scott WK, Agarwal A, Kovach JL, Schwartz SG, Postel
  • 雑誌名: Proc Natl Acad Sci USA. 巻: 107 ページ: 7401-6