The molecular pathogenesis for age-related macular degeneration and establishment of novel treatment

2013 Fiscal Year Final Research Report

• Project/Area Number: 22390322
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OHNO-MATSUI Kyoko 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (30262174)
• Co-Investigator(Kenkyū-buntansha): MORITA Ikuo 東京医科歯科大学, 医歯学総合研究科, 教授 (60100129) ; MOCHIZUKI Manabu 東京医科歯科大学, 医学部, 教授 (10010464)
• Project Period (FY): 2010-04-01 – 2013-03-31
• Keywords: 加齢黄斑変性 / ドルーゼン / 網膜色素上皮 / 脈絡膜新生血管 / Amyloid beta / neprilysin / Bruch膜

Research Abstract

We previously demonstrated that Alzheimer's amyloid beta was an important causative factor for developing the age-related macular degeneration (AMD) by using neprilysin-deficient mice. Although this mouse developed the features of early AMD, such as the degeneration of retinal pigment epithelium (RPE) and drusen deposition, they did not develop the choroidal neovascularization, which was an important feature for late stage AMD. Thus, in the present study, we focused on the integrity of Bruch's membrane as well as a role of endothelial progenitor cells. As a key factor for disrupted integrity of Bruch's membrane, we examined the role of cathepsin L and HTRA-1 in the development of late stage AMD.

Research Products

• [Journal Article] A Randomized Controlled Study of Ranibizumab in Patients with Choroidal Neovascularization Secondary to Pathologic Myopia (2014)
  • Author(s): Wolf S, Balciuniene VJ, Laganovska G, Menchini U, Ohno-Matsui K, Sharma T, Wong TY, Silva R, Pilz S, Gekkieva M; RADIANCE Study Group. RADIANCE
  • Journal Title: Ophthalmology Volume: 121(3) Pages: 682-692
  • Peer Reviewed
• [Journal Article] Evaluation of Pigment Epithelium-derived Factor and Complement Factor I Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes (2013)
  • Author(s): Miyake M, Yamashiro K, Nakanishi H, Nakata I, Akagi-Kurashige Y, Kumagai K, Oishi M, Tsujikawa A, Moriyama M, Ohno-Matsui K, Mochizuki M, Yoshimura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 54(6) Pages: 4208-4212
  • Peer Reviewed
• [Journal Article] Two Year Outcomes of Intravitreal Bevacizumab for Choroidal Neovascularization in Japanese Patients with Pathological Myopia (2012)
  • Author(s): Hayashi K, Shimada N, Moriyama M, Hayashi W, Tokoro T, Ohno-Matsui K
  • Journal Title: RETINA Volume: 32 Pages: 687-695
  • Peer Reviewed
• [Journal Article] Cholesterol enhances amyloidβdeposition in mouse retina by modulating the activities of Aβ-regulating enzymes in retinal pigment epithelial cells (2012)
  • Author(s): Wang J, Ohno-Matsui K, Morita I
  • Journal Title: Biophys Biochem Res Commun Volume: 424 Pages: 704-709
  • Peer Reviewed
• [Journal Article] Elevated amyloidβproduction in senescent retinal pigment epithelium, a possible mechanism of age-related subretinal accumulation of amyloidβ (2012)
  • Author(s): Wang J, Ohno-Matsui K, Morita I
  • Journal Title: Biochem Biophys Res Commun Volume: 423 Pages: 73-78
  • Peer Reviewed
• [Journal Article] Amyloid beta enhances migration of endothelial progenitor cells by upregulating CX3CR1 in response to fractalkine,which may be associated with development of choroidal neovascularization (2011)
  • Author(s): Wang J, Ohno-Matsui K, Nakahama K, Okamoto A, Yoshida T, Shimada N, Mochizuki M, Morita I
  • Journal Title: Jul Volume: 31(7) Pages: e11-8
  • Peer Reviewed
• [Journal Article] Characteristics of periconus choroidal neovascularization in pathological myopia (2011)
  • Author(s): Nagaoka N, Shimada N, Hayashi W, Hayashi K, Moriyama M, Yoshida T, Tokoro T, Ohno-Matsui K
  • Journal Title: Am J Ophthalmol Volume: 152(3) Pages: 420-427
  • Peer Reviewed
• [Journal Article] Development of Macular Detachment after Successful Intravitreal Bevacizumab for Myopic Choroidal Neovascularization (2011)
  • Author(s): Shimada N, Hayashi K, Yoshida T, Tokoro T, Ohno-Matsui K
  • Journal Title: Jpn J Ophthalmol Volume: 55(4) Pages: 378-382
  • Peer Reviewed
• [Journal Article] Correlation between visual prognosis and fundus autofluorescence and optical coherence tomographic findings in highly myopic eyes with submacular hemorrhage and without choroidal neovascularization (2011)
  • Author(s): Moriyama M, Ohno-Matsui K, Shimada N, Hayashi K, Kojima A, Yoshida T, Tokoro T, Mochizuki M
  • Journal Title: RETINA Volume: 31 Pages: 74-80
  • Peer Reviewed
• [Presentation] Retina Subspecialty day : Choroidal Neovascularization Secondary to Pathologic Myopia (2013)
  • Author(s): Kyoko Ohno-Matsui
  • Organizer: The American Academy of Ophthalmology(米国眼科会議)
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2013-11-16
• [Presentation] The potential role of amyloidβin the development of choroidal neovascularization in age-relaed macular degeneration (2011)
  • Author(s): Kyoko Ohno-Matsui
  • Organizer: Syymposium"Fundamental mechanism underlying both physiological and pathological angiogenesis". The 19th Annual Meeting of the Japanese Vascular Biology and Medicine Organization and the 1st Asia-Pacific Vascular Biology Meeting
  • Place of Presentation: Tokyo
  • Year and Date: 2011-12-09
• [Presentation] Anti-VEGF for myopic choroidal neovascularization (2011)
  • Author(s): Kyoko Ohno-Matsui
  • Organizer: In symposium"Are all anti-VEGFs drugs the same?"Asia Pacific Academy of Ophthalmology Congress 2011
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2011-03-22