September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Young bone marrow Sca-1+ stem cells home to aged retina and protect retina from acute glaucoma injury
Author Affiliations & Notes
  • Zhengbo Shao
    The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Jie Wu
    Basic Medical Science Institute of Harbin Medical University, Harbin, Heilongjiang, China
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Guoqing Du
    The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Huifang Song
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Shu-Hong Li
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Sheng He
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Jiao Li
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Jun Wu
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Richard D. Weisel
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Huiping Yuan
    The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
  • Ren-Ke Li
    Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships   Zhengbo Shao, None; Jie Wu, None; Guoqing Du, None; Huifang Song, None; Shu-Hong Li, None; Sheng He, None; Jiao Li, None; Jun Wu, None; Richard D. Weisel, None; Huiping Yuan, None; Ren-Ke Li, None
  • Footnotes
    Support  The Canadian Institutes of Health Research Foundation grant # 143323 to Ren-Ke Li; National Natural Science Foundation of China #81500713 to Zhengbo Shao; National Natural Science Foundation of China #81271000 and #81470634 to Huiping Yuan.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Zhengbo Shao, Jie Wu, Guoqing Du, Huifang Song, Shu-Hong Li, Sheng He, Jiao Li, Jun Wu, Richard D. Weisel, Huiping Yuan, Ren-Ke Li; Young bone marrow Sca-1+ stem cells home to aged retina and protect retina from acute glaucoma injury. Invest. Ophthalmol. Vis. Sci. 201657(12):.

      Download citation file:


      © 2017 Association for Research in Vision and Ophthalmology.

      ×
  • Supplements
Abstract

Purpose : Glaucoma is a major clinical ocular disorder, especially prevalent in the aged population. Retinal ganglion cell (RGC) apoptosis and optic nerve degeneration in aged glaucoma patients typically result in blindness. Recently, we demonstrated that young bone marrow (BM) stem cells can regenerate aged tissue and enhance tissue repair. This study investigated whether BM-derived stem cell homing to the retina increased regeneration/repair mechanisms in the retina using a mouse model of this neurodegenerative disease.

Methods : Young BM stem cell antigen 1 (Sca-1+) and Sca-1- cells from GFP+ mice (2-3 months old) were isolated by immunomagnetic cell sorting and transplanted into lethally-irradiated aged recipient mice (20-22 months old) to generate Sca-1+ [Y(Sca1+)-O] and Sca-1- [Y(Sca1-)-O] chimeras. Homing efficiency of Sca-1 cells in chimeric aged mice was evaluated by immunostaining. Acute ocular hypertensive glaucoma was induced 8 weeks after BM reconstitution and vision function was evaluated by the light/dark exploration and optomoter tests. Western blot and RT-qPCR were performed for mechanistic analyses.

Results : The light/dark exploration and optomoter tests showed better preservation of visual function in Sca-1+ than Sca-1- chimeras (p<0.05, n=10/group) 7 days after induction of acute ocular hypertension. Sca-1+ cells had greater capability to home to the retina (p<0.01, n=4-6/group) than Sca-1- cells. There was more cell differentiation into glia, microglia and neural cells in the Sca-1+ than Sca-1- group (p<0.05, n=4) after retinal injury. Furthermore, Sca-1+ cells in the retina prevented cellular apoptosis of host retinal cells (p<0.01, n=6/group). Exploration of potential mechanisms revealed that fibroblast growth factor 2 (FGF2) expression increased significantly in Sca-1+ chimeras compared to Sca-1- chimeras after acute glaucoma injury. In vitro study also demonstrated that Sca-1+ cells had higher expression levels of FGF2 (both mRNA and protein) than Sca-1- cells (p<0.01). After application of an FGF2-neutralizing antibody, activation of the Akt pathway was blocked, and the beneficial effects of Sca-1+ cells were lost.

Conclusions : Homed BM Sca-1 cells in the retina prevented cellular apoptosis after acute glaucoma injury in aged mice. FGF2 and its signal pathway may play an important role in BM Sca-1 cell-mediated retinal neuroprotection.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

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.

×