Transplanted Oligodendrocyte Precursor Cells Reduce Neurodegeneration in a Model of Glaucoma

PURPOSE. Glaucoma is a common neurodegenerative disease for which current therapies are often insufficient; thus, new neuroprotective strategies are an important goal. Stem cells are attracting increasing attention as mediators of neuroprotection, often conferred via the trophic support of injured neurons. The purpose of our investigation was to determine whether oligodendrocyte precursor cells (OPCs), a type of neural stem cell, can protect retinal ganglion cells (RGCs) from glaucomatous damage in vivo. METHODS. Intraocular pressure was chronically increased by trabecular laser treatment delivered unilaterally to adult rat eyes. OPCs were isolated in vitro and then transplanted intravitreally either before, or concurrent with, injury induction. Survival, migration, differentiation, and integration of grafted cells were assessed by immunohistochemistry. RGC survival was assessed by optic nerve axon quantification. RESULTS. Transplanted OPCs were found to survive within the eye for at least 12 weeks and to localize close to the RGCs. Moreover, OPCs significantly enhanced the survival of RGCs in the glaucomatous eye, but only when concomitantly activated by inflammation. Axonal loss relative to the untreated fellow eye was 28.34% +/- 11.51% in eyes that received activated OPCs, compared with 60.34% +/- 8.28% in control eyes (mean +/- SEM; P = 0.05). Amelioration of RGC death was not attributable to inflammation but relied on an interaction between inflammatory cells and OPCs. Engrafted cells also displayed multipotentiality in vivo. CONCLUSIONS. The impressive neuroprotection conferred by OPCs in this model suggests stem cell-based therapies should be explored further as a potential treatment for glaucoma. (Invest Ophthalmol Vis Sci. 2009;50:4244-4253) DOI: 10.1167/iovs.08-3239