Transplanted oligodendrocyte precursor cells reduce neurodegeneration in a model of glaucoma.
OBJECTIVE
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.
Bull
Natalie D
ND
Centre for Brain Repair and National Institute for Health Research)Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom.
Irvine
Karen-Amanda
KA
Franklin
Robin J M
RJ
Martin
Keith R
KR
D000818:Animals; D001369:Axons / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D005901:Glaucoma / Q000628:therapy*; D007429:Intraocular Pressure; D008297:Male; D019636:Neurodegenerative Diseases / Q000628:therapy*; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D009900:Optic Nerve / Q000166:cytology; D009901:Optic Nerve Diseases / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
D015415:Biomarkers