Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion

Access this Article

Author(s)

    • Okuda Hiroaki
    • Department of Anatomy and Neuroscience, Nara Medical University Faculty of Medicine
    • Tatsumi Kouko
    • Department of Anatomy and Neuroscience, Nara Medical University Faculty of Medicine
    • Morita Shoko
    • Department of Anatomy and Neuroscience, Nara Medical University Faculty of Medicine
    • Ogata Nahoko
    • Department of Ophthalmology, Nara Medical University Faculty of Medicine
    • Wanaka Akio
    • Department of Anatomy and Neuroscience, Nara Medical University Faculty of Medicine

Abstract

Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration.

Journal

  • ACTA HISTOCHEMICA ET CYTOCHEMICA

    ACTA HISTOCHEMICA ET CYTOCHEMICA 49(2), 67-74, 2016

    JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY

Codes

  • NII Article ID (NAID)
    130005149556
  • Text Lang
    ENG
  • ISSN
    0044-5991
  • Data Source
    J-STAGE 
Page Top