Therapeutic potential of semaphorin 3E for the treatment of choroidal neovascularization

• Project/Area Number: 24791847
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kyoto University
• Principal Investigator: OISHI Akio 京都大学, 医学(系)研究科(研究院), 助教 (50572955)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脈絡膜新生血管 / semaphorin3E / plexinD1 / PlexinD1 / Semaphorin3E / 眼生化学・分子生物学

Research Abstract

We performed the study to investigate the effects of Semaphorin3E (Sema3E)/PlexinD1 signal in the development of choroidal neovascularization (CNV) and explore the therapeutic potential of the pathway. We used a laser-induced CNV model in mouse. The presence of PlexinD1 was confirmed immunohistochemically in the endothelial cells of CNV. Intravitreal injection of recombinant Sema3E decreased the CNV size in a dose-dependent manner. This inhibitory effect of Sema3E in the formation of CNV was canceled in the PlexinD1 knockout mice. These results indicate that Sema3E-PlexinD1 signal is involved in the development of CNV and stimulation of the pathway has the therapeutic potential for CNV.

Research Products

• [Journal Article] Macular Choroidal Thickness and Volume of Eyes with Reticular Pseudodrusen Using Swept-Source Optical Coherence Tomography (2014)
  • Author(s): Ueda-Arakawa N, Ooto S, Ellabban AA, Takahashi A, Oishi A, Tamura H, Yamashiro K, Tsujikawa A, Yoshimura N
  • Journal Title: Am J Ophthalmol Volume: (in press)
• [Journal Article] LAPTOP Study : A 24-Month Trial of Verteporfin Versus Ranibizumab for Polypoidal Choroidal Vasculopathy (2014)
  • Author(s): Oishi A, Miyamoto N, Mandai M, Honda S, Matsuoka T, Oh H, Kita M, Nagai T, Bessho N, Uenishi M, Kurimoto Y, Negi A
  • Journal Title: Ophthalmology Volume: (in press)
• [Journal Article] Multimodal evaluation of macular function in age-related macular degeneration (2014)
  • Author(s): Ogino K, Tsujikawa A, Yamashiro K, Ooto S, Oishi A, Nakata I, Miyake M, Takahashi A, Ellabban AA, Yoshimura N
  • Journal Title: Jpn J Ophthalmol Volume: (in press)
• [Journal Article] Vascular Endothelial Growth Factor Gene and the Response to Anti-Vascular Endothelial Growth Factor Treatment for Choroidal Neovascularization in High Myopia (2014)
  • Author(s): Miyake M, Yamashiro K, Akagi-Kurashige Y, Kumagai K, Nakata I, Nakanishi H, Oishi A, Tsujikawa A, Yamada R, Matsuda F, Yoshimura N
  • Journal Title: Ophthalmology Volume: 121(1) Pages: 225-33
• [Journal Article] Reduction of Retinal Sensitivity in Eyes With Reticular Pseudodrusen (2013)
  • Author(s): Ooto S, Ellabban AA, Ueda-Arakawa N, Oishi A, Tamura H, Yamashiro K, Tsujikawa A, Yoshimura N
  • Journal Title: Am J Ophthalmol Volume: 156(6) Pages: 1184-1191
• [Journal Article] Nagahama Study Group. Association between the cholesteryl ester transfer protein gene and polypoidal choroidal vasculopathy (2013)
  • Author(s): Nakata I, Yamashiro K, Kawaguchi T, Gotoh N, Nakanishi H, Akagi-Kurashige Y, Miyake M, Tsujikawa A, Oishi A, Saito M, Iida T, Yamada R, Matsuda F, Yoshimura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: (in press)
• [Journal Article] Comparison of the effect of ranibizumab and verteporfin for polypoidal choroidal vasculopathy : 12-month LAPTOP study results (2013)
  • Author(s): Oishi A, Kojima H, Mandai M, Honda S, Matsuoka T, Oh H, Kita M, Nagai T, Fujihara M, Bessho N, Uenishi M, Kurimoto Y, Negi A
  • Journal Title: Am J Ophthalmol Volume: 156(4) Pages: 644-51
• [Journal Article] Focal choroidal excavation in eyes with central serous chorioretinopathy (2013)
  • Author(s): Ellabban AA, Tsujikawa A, Ooto S, Yamashiro K, Oishi A, Nakata I, Miyake M, Akagi-Kurashige Y, Ueda-Arakawa N, Arichika S, Yoshitake S, Takahashi A, Yoshimura N
  • Journal Title: Am J Ophthalmol Volume: 156(4) Pages: 673-83
• [Journal Article] Intravitreal injection of ranibizumab for recovery of macular function in eyes with subfoveal polypoidal choroidal vasculopathy (2013)
  • Author(s): Ogino K, Tsujikawa A, Yamashiro K, Ooto S, Oishi A, Nakata I, Miyake M, Yoshimura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 54(5) Pages: 3771-9
• [Journal Article] Sensitivity and specificity of detecting reticular pseudodrusen in multimodal imaging in Japanese patients (2013)
  • Author(s): Ueda-Arakawa N, Ooto S, Tsujikawa A, Yamashiro K, Oishi A, Yoshimura N
  • Journal Title: Retina Volume: 33(3) Pages: 490-7
• [Journal Article] Recovery of photoreceptor outer segments after anti-VEGF therapy for age-related macular degeneration (2013)
  • Author(s): Oishi A, Shimozono M, Mandai M, Hata M, Nishida A, Kurimoto Y
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 251(2) Pages: 435-40
  • NAID: 120005474470
• [Journal Article] Long-term effect of intravitreal injection of anti-VEGF agent for visual acuity and chorioretinal atrophy progression in myopic choroidal neovascularization (2013)
  • Author(s): Oishi A, Yamashiro K, Tsujikawa A, Ooto S, Tamura H, Nakata I, Miyake M, Yoshimura N
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 251(1) Pages: 1-7
  • NAID: 120005241384
• [Journal Article] Prevalence and genomic association of reticular pseudodrusen in age-related macular degeneration (2012)
  • Author(s): Ueda-Arakawa N, Ooto S, Nakata I, Yamashiro K, Tsujikawa A, Oishi A, Yoshimura N
  • Journal Title: Am J Ophthalmol Volume: 155(2) Pages: 260-269
• [Journal Article] Macular choroidal thickness measured by swept source optical coherence tomography in eyes with inferior posterior staphyloma (2012)
  • Author(s): Ellabban AA, Tsujikawa A, Matsumoto A, Yamashiro K, Oishi A, Ooto S, Nakata I, Akagi-Kurashige Y, Miyake M, Yoshimura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53(12) Pages: 7735-45
• [Journal Article] Choroidal thickness after intravitreal ranibizumab injections for choroidal neovascularization (2012)
  • Author(s): Ellabban AA, Tsujikawa A, Ogino K, Ooto S, Yamashiro K, Oishi A, Yoshimura N
  • Journal Title: Clin Ophthalmol Volume: 6 Pages: 837-44
• [Journal Article] Choroidal thickness, vascular hyperpermeability, and complement factor H in age-related macular degeneration and polypoidal choroidal vasculopathy (2012)
  • Author(s): Jirarattanasopa P, Ooto S, Nakata I, Tsujikawa A, Yamashiro K, Oishi A, Yoshimura N.
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53(7) Pages: 3663-72
• [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 Volume: 250(8) Pages: 1129-36
• [Journal Article] Significance of C2/CFB variants in age-related macular degeneration and polypoidal choroidal vasculopathy in a Japanese population (2012)
  • Author(s): Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanshi H, Hayashi H, Akagi-Kurashige Y, Tsujikawa A, Otani A, Saito M, Iida T, Oishi A, Matsuo K, Tajima K, Matsuda F, Yoshimura N
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 53 Pages: 794-798
• [Journal Article] Therapeutic potential of semaphorin 3E for the treatment of choroidal neovascularization
  • Author(s): Kenji Suda, Congrong Guo, Akio Oishi, Shinya Ikeda, Akiyoshi Uemura, Nagahisa Yoshimura
  • Journal Title: Invest Ophthalmol Vis Sci Volume: (in press)
• [Presentation] Semaphorin3E/PlexinD1 シグナル経路による脈絡膜新生血管形成の抑制効果 (2013)
  • Author(s): 須田謙史, 大石明生, ら
  • Organizer: 厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究斑
  • Place of Presentation: 名古屋
• [Presentation] Semaphorin3E/PlexinD1 シグナル経路による脈絡膜新生血管形成の抑制効果 (2013)
  • Author(s): 須田謙史, 郭从容, 大石明生, ら
  • Organizer: 第117回二本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] Semaphorin3E/PlexinD1シグナル経路による脈絡膜新生血管形成の抑制効果. (2013)
  • Author(s): 須田謙史、郭从容、大石明生、池田真也、吉村長久
  • Organizer: 第117回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] Semaphorin3E/PlexinD1シグナル経路による脈絡膜新生血管形成の抑制効果 (2013)
  • Author(s): 須田謙史、大石明生 他
  • Organizer: 厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究斑
  • Place of Presentation: 名古屋