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Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
07:32

Assessment of Vascular Regeneration in the CNS Using the Mouse Retina

Published on: June 23, 2014

The role of the NFAT signaling pathway in retinal neovascularization

Colin A Bretz1, Sara Savage, Megan Capozzi

  • 1Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.

Investigative Ophthalmology & Visual Science
|September 21, 2013
PubMed
Abstract

Insights

Nuclear factor of activated T cells (NFAT) signaling drives angiogenic behaviors in human retinal cells. Inhibiting NFAT effectively reduces abnormal blood vessel growth in oxygen-induced retinopathy, suggesting NFAT as a therapeutic target for neovascular eye diseases.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Cell Biology

Background:

  • Vascular Endothelial Growth Factor (VEGF) signaling is crucial for angiogenesis.
  • The transcription factor Nuclear Factor of Activated T cells (NFAT) is activated downstream of VEGF.
  • NFAT's role in the angiogenic cell behaviors of human retinal microvascular endothelial cells (HRMEC) requires further investigation.

Purpose of the Study:

  • To investigate the role of NFAT in the angiogenic cell behaviors of HRMEC.
  • To assess the efficacy of NFAT signaling inhibitors in a rat model of oxygen-induced retinopathy (OIR).

Main Methods:

  • HRMEC were treated with VEGF and the NFAT inhibitor INCA-6; NFAT translocation was assessed via immunocytochemistry.
  • HRMEC proliferation and tube formation were evaluated after treatment with varying doses of INCA-6.
  • Rats with OIR received INCA-6 or FK-506 (a calcineurin inhibitor); retinal neovascular area was measured.

Main Results:

  • VEGF induced NFATc1 translocation to the nucleus in HRMEC, which was blocked by INCA-6.
  • INCA-6 inhibited HRMEC proliferation and tube formation in a dose-dependent manner.
  • Both INCA-6 and FK-506 significantly reduced pathologic neovascularization in the OIR model.

Conclusions:

  • NFATc1 activation downstream of VEGF signaling plays a key role in HRMEC angiogenic behaviors.
  • NFAT inhibition demonstrates high efficacy in an OIR model.
  • The NFAT signaling pathway represents a potential therapeutic target for neovascular eye diseases.
Keywords:
NFATneovascularizationoxygen-induced retinopathyretinal microvascular endothelial cellstranscription factors

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