Angiotensin II type 1 receptor blockade suppresses light-induced neural damage in the mouse retina.

• Project/Area Number: 24592648
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Keio University
• Principal Investigator: KOTO Takashi 慶應義塾大学, 医学部, 講師 (60464814)
• Co-Investigator(Kenkyū-buntansha): OZAWA Yoko 慶應義塾大学, 医学部 眼科学教室, 講師 (90265885)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 網膜 / 光障害 / 神経変性

Outline of Final Research Achievements

We examined the role of angiotensin II type 1 receptor (AT1R) signaling, which is part of the renin-angiotensin system, in light-induced retinal damage. Light-exposed Balb/c mice that were treated with the AT1R blockers (ARBs) before and after the light exposure exhibited attenuated visual function impairment, compared to vehicle-treated mice. Further evaluation of an ARB, valsartan, showed that it suppressed a number of light-induced retinal effects, including thinning of the photoreceptor cell layer caused by apoptosis, shortening of the photoreceptor cell outer segment, and increased levels of reactive oxygen species (ROS). The ARB suppressed the induction of c-fos and the upregulation of fasl after light exposure. Our results suggest that AT1R signaling mediates light-induced apoptosis, by increasing the levels of ROS and proapoptotic molecules in the retina. Thus, AT1R blockade may represent a new therapeutic approach for preventing light-induced retinal neural damage.

Research Products

• [Journal Article] Association of macular pigment optical density with serum concentration of oxidized low-density lipoprotein in healthy adults. (2015)
  • Author(s): Nagai N, Izumi-Nagai K, Suzuki M, Shinoda H, Koto T, Uchida A, Mochimaru H, Tomita Y, Miyake S, Kobayashi S, Sasaki M, Tsubota K, Ozawa Y.
  • Journal Title: Retina Volume: 35(4) Issue: 4 Pages: 820-826
  • DOI: 10.1097/iae.0000000000000382
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Early Signs of Exudative Age-related Macular Degeneration in Asians (2014)
  • Author(s): Sasaki M, Kawasaki R, Uchida A, Koto T, Shinoda H, Tsubota K, Tien Yin Wong, Ozawa Y
  • Journal Title: Optometry and Vision Science. Volume: 91 Issue: 8 Pages: 849-853
  • DOI: 10.1097/opx.0000000000000317
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of Maternal Age to Development and Progression of Retinopathy of Prematurity in Infants of Gestational Age under 33 Weeks. (2014)
  • Author(s): Uchida A, Miwa M, Shinoda H, Koto T, Nagai N, Mochimaru H, Tomita Y, Sasaki M, Ikeda K, Tsubota K, Ozawa Y
  • Journal Title: J Ophthalmol. Volume: 2014 Pages: 187929-187929
  • DOI: 10.1155/2014/187929
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ozawa Predictive factors for non-responders to intravitreal ranibizumab treatment in age-related macular degeneration (2014)
  • Author(s): Suzuki M, Nagai N, Izumi-Nagai K, Shinoda H, Koto T, Uchida A, Mochimaru H, Yuki K, Sasaki M, Tsubota K
  • Journal Title: Br J Ophthalmol Volume: 98 Issue: 9 Pages: 7-7
  • DOI: 10.1136/bjophthalmol-2013-304670
  • Peer Reviewed / Open Access
• [Journal Article] Association of Serum Lipids with Macular Thickness and Volume in Type 2 Diabetes without Diabetic Macular Edema. (2014)
  • Author(s): Sasaki M, Kawashima M, Kawasaki R, Uchida A, Koto T, Shinoda H, Tsubota K, Jie Jin Wang, Ozawa Y
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 55 Issue: 3 Pages: 1749-1753
  • DOI: 10.1167/iovs.13-13035
  • Peer Reviewed
• [Journal Article] Vitrectomy for myopic foveoschisis with internal limiting membrane peeling and no gas tamponade. (2013)
  • Author(s): Uchida A, Shinoda H, Koto T, Mochimaru H, Nagai N, Tsubota K, Ozawa Y
  • Journal Title: Retina. Volume: 34 Issue: 3 Pages: 455-460
  • DOI: 10.1097/iae.0b013e3182a0e477
  • Peer Reviewed
• [Journal Article] Detection of Early Visual Impairment in Patients with Epiretinal Membrane. (2013)
  • Author(s): Nishi Y, Shinoda H, Uchida A, Koto T, Mochimaru H, Nagai N, Tsubota K, Ozawa Y.
  • Journal Title: Acta Ophthalmologica Volume: Epub ahead of print Issue: 5 Pages: 1-5
  • DOI: 10.1111/aos.12060
  • Peer Reviewed
• [Journal Article] Usage of micronutrient supplement for preventing advanced Age-related Macular Degeneration in Japan (2012)
  • Author(s): Sasaki M, Shinoda H, Koto T, Uchida A, Tsubota K, Ozawa Y
  • Journal Title: Archives of Ophthalmology Volume: 130(2) Issue: 2 Pages: 254-5
  • DOI: 10.1001/archopthalmol.2011.1368
  • Peer Reviewed
• [Presentation] Levels of immunoglobulins (Igs) in hematological (2014)
  • Author(s): Kurihara T, Shinoda H, Yagihashi M, Uchida A, Inoue M, Takashi Koto T, Nagai N, Tsubota K, Ozawa Y.
  • Organizer: ASRS 32nd Annual Meeting
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2014-08-09 – 2014-08-13
• [Presentation] 狭義加齢黄斑変性に対するpro re nateによるラニビズマブ硝子体注射. (2013)
  • Author(s): 鈴木美砂, 永井紀博, 永井香奈子, 篠田肇, 内田敦郎, 厚東隆志, 持丸博史, 富田洋平, 佐々木真理子, 坪田一男, 小沢洋子.
  • Organizer: 第67回日本臨床眼科学会
  • Place of Presentation: パシフィコ横浜 神奈川県 横浜市
• [Presentation] Associations of Serum Lipids with Macular Morphology in Patients without Diabetic Macular Edema.
  • Author(s): Sasaki M, Kawashima M, Kawasaki R, Kawai M, Uchida A, Koto T, Mochimaru H, Shinoda H, Jie Jin Wang, Tsubota K, Ozawa Y.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
  • Place of Presentation: Washington State Convention & Trade Center Seattle, USA,
• [Presentation] Baseline characteristics and response to intravitreal ranibizumab therapy for age-related macular degeneration.
  • Author(s): Suzuki M, Nagai N, Izumi-Nagai K, Shinoda H, Koto T, Uchida A, Mochimaru H, Yuki K, Tsubota K, Ozawa Y.
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
  • Place of Presentation: Washington State Convention & Trade Center Seattle, USA,