Abstract
PURPOSE. To determine long-term safety of intravitreal administration of good manufacturing practice (GMP)-grade human bone-marrow-derived CD34 + cells in NOD-SCID (nonobese diabetic-severe combined immunodeficiency) mice with acute retinal ischemia-reperfusion injury, a model for retinal vasculopathy. METHOD. Acute ischemia-reperfusion injury was induced in the right eye of adult NOD-SCID mice (n = 23) by transient elevation of intraocular pressure. Seven days later, 12 injured eyes and 5 normal contralateral eyes were injected each intravitreally with 5 × 10 4 CD34 + cells isolated under GMP conditions from a healthy human donor bone marrow using an immunomagnetic cell isolation system. The remaining 11 injured eyes were not treated and served as controls. Mice were euthanized 1 day, 4 months, and 8 months later. Both eyes were enucleated and examined by immunohistochemical analysis and hematoxylin and eosin staining. Among mice followed for 8 months, electroretinography (ERG) was performed on both eyes before euthanization. All major organs were examined grossly and histologically after serial sectioning. RESULTS. Immunohistochemical staining 4 months after injection showed detectable CD34 + cells in the retinal vasculature. ERG at 8 months after CD34 + cell injection showed signals that were similar in untreated eyes. Histology of the enucleated eyes injected with CD34 + cells showed no intraocular tumor or abnormal tissue growth after 8 months. Histologic analysis of all major organs showed no abnormal proliferation of human cells. 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. A clinical trial will start to further explore this therapy.
Original language | English (US) |
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Pages (from-to) | 986-994 |
Number of pages | 9 |
Journal | Investigative Ophthalmology and Visual Science |
Volume | 53 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2012 |
ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
- Medicine(all)