Personalized medicine for age-related macular degeneration

2011 Fiscal Year Final Research Report

• Project/Area Number: 21249084
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyoto University
• Principal Investigator: YOSHIMURA Nagahisa 京都大学, 医学研究科, 教授 (70211662)
• Co-Investigator(Kenkyū-buntansha): OTANI Atsushi 京都大学, 医学研究科, 講師 (30314222) ; YAMASHIRO Kenji 京都大学, 医学研究科, 助教 (80399617) ; YAMADA Ryo 京都大学, 医学研究科, 教授 (50301106)
• Project Period (FY): 2009 – 2011
• Keywords: 眼細胞生物学

Research Abstract

We successfully made quick detection kit for ARMS2 A69S single nucleotide polymorphism. We used this kit for our out-patients and made sure that it is practically usable for clinic. Since A69S genotype was associated with the visual outcome after photodynamic therapy but to with the visual outcome after anti-VEGF therapy, A69S genotype would determine which patients should be treated with photodynamic therapy, and which patients should be treated with anti-VEGF drug. In addition to ARMS2, we found that VEGF gene and PEDF gene were associated with the response to treatment for are-related macular degeneration.

Research Products

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