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A Mouse Model for Laser-induced Choroidal Neovascularization
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Effect of integrin α5β1 inhibition on SDF-l/CXCR4-mediated choroidal neovascularization

Yang Lyu1,2, Wen-Qin Xu1, Li-Juan Sun1

  • 1Department of Ophthalmology, Eye Institute of China PLA, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.

International Journal of Ophthalmology
|June 5, 2018
PubMed
Abstract

Insights

Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 promote choroidal neovascularization (CNV) by increasing integrin α5β1 expression in endothelial cells. Inhibiting CXCR4 or integrin α5β1 effectively reduces CNV progression.

Area of Science:

  • Ophthalmology
  • Vascular Biology
  • Cell Signaling

Background:

  • Choroidal neovascularization (CNV) is a major cause of vision loss.
  • The stromal cell-derived factor-1 (SDF-1)/CXCR4 axis and integrins are implicated in CNV pathogenesis.

Purpose of the Study:

  • To investigate the role of integrins in CNV.
  • To explore the association between integrins and the SDF-1/CXCR4 axis in CNV.

Main Methods:

  • CNV was induced in mice using laser photocoagulation.
  • Animals were treated with SDF-1, a CXCR4 inhibitor (AMD3100), or an integrin α5β1 inhibitor (ATN161).
  • CNV progression was assessed using HE staining, FFA, and OCT; protein expression was analyzed via Western blot and immunofluorescence. In vitro studies used hypoxia-exposed endothelial cells.

Main Results:

  • SDF-1 treatment significantly promoted CNV progression.
  • Inhibitors of CXCR4 (AMD3100) and integrin α5β1 (ATN161) significantly reduced CNV size, thickness, and leakage.
  • SDF-1 increased integrin α5 and CXCR4 expression in vivo and in vitro; AMD3100 and ATN161 treatments decreased these levels and inhibited endothelial cell migration and tube formation.

Conclusions:

  • SDF-1/CXCR4 signaling drives CNV by upregulating integrin α5β1 expression in endothelial cells.
  • Targeting the SDF-1/CXCR4 axis or integrin α5β1 presents a potential therapeutic strategy for CNV.
Keywords:
CXCR4choroidal neovascularizationendothelial cellshypoxiaintegrin α5β1stromal cell-derived factor-1

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