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N. D. Bull, K. A. Irvine, R. J. M. Franklin, K. R. Martin; Intravitreal Transplantation of Oligodendrocyte Precursor Cells Increases Retinal Ganglion Cell Survival in a Rat Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4064.
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Oligodendrocyte precursor cells (OPCs) have previously been shown to myelinate retinal ganglion cell (RGC) axons when transplanted intravitreally. The extent of myelination is enhanced in the presence of zymosan. We investigated whether transplantation of OPCs can reduce RGC death in a rat glaucoma model.
OPCs were isolated and cultured from the cortices of P0 Lewis rat pups. Adult Lewis rats received intravitreal transplantation of either OPCs plus zymosan (n=9) or zymosan alone (n=9). Eight weeks after transplantation, experimental glaucoma was induced in the transplanted eye by 532nm trabecular laser treatment. Optic nerve axon survival was quantified after 4 weeks of experimental glaucoma and immunohistochemical techniques were used to assess OPC/oligodendrocyte survival and myelination.
Axon counts revealed that engraftment of OPCs provided significant RGC neuroprotection with 69917±9302 axons surviving in OPC plus zymosan treated eyes compared to 40671±7465 axons remaining in control zymosan treated eyes (mean±SEM; p=0.03). Axonal loss relative to the untreated fellow eye was 28.34±11.51% in OPC plus zymosan treated eyes compared to 60.34±8.28% in eyes treated with zymosan alone (mean±SEM; p=0.05). Surprisingly, immunohistochemical analysis of retinal flat-mounts showed limited myelination of RGC axons by OPCs or differentiation of OPCs into oligodendrocytes.
Intraocular engraftment of OPCs provided significant RGC neuroprotection, reducing axonal loss by about 50% after 4 weeks of glaucoma. Our observation of increased RGC survival, even when OPCs were transplanted 2 months prior to experimental IOP elevation, suggests a prolonged neuroprotective effect of this treatment.
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