A Novel Platelet-Activating Factor Receptor Antagonist Inhibits Choroidal Neovascularization and Subretinal Fibrosis

Han Zhang, Yang Yang, Atsunobu Takeda, Takeru Yoshimura, Yuji Oshima, Kohei Sonoda, Tatsuro Ishibashi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Choroidal neovascularization (CNV) is a critical pathogenesis in age-related macular degeneration (AMD), the most common cause of blindness in developed countries. To date, the precise molecular and cellular mechanisms underlying CNV have not been elucidated. Platelet-activating factor (PAF) has been previously implicated in angiogenesis; however, the roles of PAF and its receptor (PAF-R) in CNV have not been addressed. The present study reveals several important findings concerning the relationship of the PAF-R signaling with CNV. PAF-R was detected in a mouse model of laser-induced CNV and was upregulated during CNV development. Experimental CNV was suppressed by administering WEB2086, a novel PAF-R antagonist. WEB2086-dependent suppression of CNV occurred via the inhibition of macrophage infiltration and the expression of proangiogenic (vascular endothelial growth factor) and proinflammatory molecules (monocyte chemotactic protein-1 and IL-6) in the retinal pigment epithelium-choroid complex. Additionally, WEB2086-induced PAF-R blockage suppresses experimentally induced subretinal fibrosis, which resembles the fibrotic subretinal scarring observed in neovascular AMD. As optimal treatment modalities for neovascular AMD would target the multiple mechanisms of AMD-associated vision loss, including neovascularization, inflammation and fibrosis, our results suggest PAF-R as an attractive molecular target in the treatment of AMD.

Original languageEnglish
Article numbere68173
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 27 2013

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platelet-activating factor
Choroidal Neovascularization
Platelet Activating Factor
WEB 2086
angiogenesis
fibrosis
antagonists
Fibrosis
Macular Degeneration
receptors
Retinal Pigments
Chemokine CCL2
Macrophages
Infiltration
Vascular Endothelial Growth Factor A
Choroid
platelet activating factor receptor
Retinal Pigment Epithelium
Interleukin-6
Blindness

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A Novel Platelet-Activating Factor Receptor Antagonist Inhibits Choroidal Neovascularization and Subretinal Fibrosis. / Zhang, Han; Yang, Yang; Takeda, Atsunobu; Yoshimura, Takeru; Oshima, Yuji; Sonoda, Kohei; Ishibashi, Tatsuro.

In: PLoS One, Vol. 8, No. 6, e68173, 27.06.2013.

Research output: Contribution to journalArticle

Zhang, Han ; Yang, Yang ; Takeda, Atsunobu ; Yoshimura, Takeru ; Oshima, Yuji ; Sonoda, Kohei ; Ishibashi, Tatsuro. / A Novel Platelet-Activating Factor Receptor Antagonist Inhibits Choroidal Neovascularization and Subretinal Fibrosis. In: PLoS One. 2013 ; Vol. 8, No. 6.
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