April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Long-term Effects of Intravitreal Administration of GMP-grade Human Bone Marrow-derived CD34+ Cells in NOD-SCID Mice with Acute Retinal Ischemia-Reperfusion Injury
Susanna S. Park; Sergio Caballero, Jr.; Bradley Shibata; Gerhard Bauer; Kristina I. Forward; David G. Telander; Paul G. FitzGerald; Maria B. Grant; Jan Nolta
Author Affiliations & Notes
  • Susanna S. Park
    Ophthalmology & Vision Science, Univ of California Davis Eye Ctr, Sacramento, California
  • Sergio Caballero, Jr.
    Pharmacology/Therapeutics,
    University of Florida, Gainesville, Florida
  • Bradley Shibata
    Cell Biol & Human Anatomy, Univ of California-Davis, Davis, California
  • Gerhard Bauer
    Institute for Regenerative Cures, Univ of California Davis, Sacramento, California
  • Kristina I. Forward
    Ophthalmology & Vision Science, Univ of California Davis Eye Ctr, Sacramento, California
  • David G. Telander
    Ophthalmology & Vision Science, Univ of California Davis Eye Ctr, Sacramento, California
  • Paul G. FitzGerald
    Cell Biol & Human Anatomy, Univ of California-Davis, Davis, California
  • Maria B. Grant
    Pharmacology and Therapeutics,
    University of Florida, Gainesville, Florida
  • Jan Nolta
    Institute for Regenerative Cures, Univ of California Davis, Sacramento, California
  • Footnotes
    Commercial Relationships  Susanna S. Park, None; Sergio Caballero, Jr., None; Bradley Shibata, None; Gerhard Bauer, None; Kristina I. Forward, None; David G. Telander, None; Paul G. FitzGerald, None; Maria B. Grant, None; Jan Nolta, None
  • Footnotes
    Support  Research to Prevent Blindness Unrestricted Departmental Grant
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2575. doi:
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      Susanna S. Park, Sergio Caballero, Jr., Bradley Shibata, Gerhard Bauer, Kristina I. Forward, David G. Telander, Paul G. FitzGerald, Maria B. Grant, Jan Nolta; Long-term Effects of Intravitreal Administration of GMP-grade Human Bone Marrow-derived CD34+ Cells in NOD-SCID Mice with Acute Retinal Ischemia-Reperfusion Injury. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2575.

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Abstract

Purpose: : To study the long-term effects of intravitreal administration of Good Manufacturing Practice (GMP)-grade human bone marrow-derived CD34+ cells in NOD-SCID mice with acute retinal ischemia-reperfusion injury in order to determine if there are any long-term safety concerns regarding using these cells intravitreally in treating eyes with retinal vasculopathy such as diabetic retinopathy or retinal vascular occlusion.

Methods: : Acute ischemia-reperfusion injury was induced in the right eye of adult NOD-SCID mice (n = 20) by elevating the intraocular pressure transiently for 2 hours to 80 - 90 mm Hg by infusing Hanks balanced saline solution into the anterior chamber under hydrostatic pressure. Seven days later, 10 injured eyes and 5 normal eyes were injected each intravitreally with 5 x 104 CD34+ cells isolated under GMP-conditions from a healthy human donor bone marrow using the Miltenyi CliniMACS system and suspended in 1 µl PBS. The remaining 10 injured eyes were injected intravitreally with 1 µl PBS. Mice were euthanized 1 day, 6 months and 8 months after intravitreal injection. Both eyes were enucleated and examined by immunohistochemical analysis and H & E staining. Among mice followed for 8 months, electroretinography (ERG) was performed on both eyes just prior to euthanization.

Results: : Immunohistochemical staining showed the presence of large numbers of CD34+ cells in the retinal vasculature 1 day after injection, with identifiable cells seen 6 months after injection. ERG at 8 months following intravitreal injection of CD34+ cells showed a signal comparable to uninjected contralateral eye. Histology of the enucleated eyes with retinal ischemia-reperfusion injury injected with CD34+ cells showed a normal retinal morphology with no intraocular tumor or abnormal tissue growth 8 months following intravitreal cell injection.

Conclusions: : Intravitreal administration of GMP-grade human bone marrow-derived CD34+ cells appears to be well tolerated long-term in eyes with acute retinal ischemic injury. Safety was demonstrated.

Keywords: ischemia • retina • vascular occlusion/vascular occlusive disease 
© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2015 Association for Research in Vision and Ophthalmology.
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