June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Bone-derived Mesenchymal Stem Cells (MSCs) promote retinal revascularization in Oxygen-Induced Retinopathy (OIR) mouse model.
Author Affiliations & Notes
  • Baraa Noueihed
    Maisonneuve-Rosemont Hospital Research Center, Montreal, QC, Canada
    Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
  • Jose Carlos Rivera
    Maisonneuve-Rosemont Hospital Research Center, Montreal, QC, Canada
    Department of Ophthalmology, Université de Montréal, Montreal, QC, Canada
  • Martine Blais
    Sainte-Justine Hospital Research Center, Montreal, QC, Canada
  • Sylvain Chemtob
    Maisonneuve-Rosemont Hospital Research Center, Montreal, QC, Canada
    Sainte-Justine Hospital Research Center, Montreal, QC, Canada
  • Footnotes
    Commercial Relationships Baraa Noueihed, None; Jose Carlos Rivera, None; Martine Blais, None; Sylvain Chemtob, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2053. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Baraa Noueihed, Jose Carlos Rivera, Martine Blais, Sylvain Chemtob; Bone-derived Mesenchymal Stem Cells (MSCs) promote retinal revascularization in Oxygen-Induced Retinopathy (OIR) mouse model.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2053.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: Retinopathy of prematurity (ROP) is the leading cause of visual impairment and blindness in premature infants. Current therapies target only aberrant intravitreal vessels without repopulating the avascular regions of the retina. Thus new therapies are needed to repair the inflicted vascular damage while preventing pathologic neovascularization (NV). Since stem cells have the ability to migrate to damaged tissue and enhance revascularization in ischemic models, we surmised that they can promote normal retinal revascularization in a mouse model of ROP by modulating angiogenic factors.

Methods: Oxygen-induced retinopathy (OIR) mouse model was used herein. Briefly, at postnatal day 7 (P7) mice are subjected to 75% O2 until P12 to induce vasoobliteration (VO) followed by room air leading to NV. Bone-derived Mesenchymal Stem cells (MSCs) are isolated from adult mice and then injected intravitreally either at the onset of VO (P7) or NV (P12) to assess prevention and repair of vascular damage respectively. VO areas were analyzed subsequently at P12 and P17. Moreover, migration of MSCs in OIR retinas was traced following injection. To determine the direct effect of MSCs on endothelial cell growth, aortic ring assay was performed in conjunction with MSCs co-culture in normoxic and hypoxic environments. Gene expression analysis by quantitative PCR was performed on OIR retinas injected with MSCs to determine possible factor(s) involved in revascularization.

Results: MSCs injected in OIR retinas at P12 (1) significantly reduced VO areas by75% and inhibited formation of neovascular tufts compared to the control, (2) migrated to the avascular regions and (3) localized adjacent to endothelial cells. In aortic ring assay, MSCs had no effect on the sprouting of endothelial cells in normoxia; however in hypoxia, MSCs restored endothelial cell growth initially curbed by low oxygen levels. Interestingly, MSC-injected OIR retinas showed an augmented expression of IGF-1, VEGF, Netrin-1, and Sema3E, and decreased expression of IL-1β and Sema3A.

Conclusions: MSCs can (1) arrest NV while inducing revascularization in the avascular areas of OIR retinas and (2) mediate vascular repair in a paracrine fashion by regulating the expression of growth factors, inflammatory cytokines and guidance cues.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×