Preferential differentiation of neural progenitor cells into the glial lineage through gp130 signaling in N-methyl-d-aspartate-treated retinas

The purpose of this study was to investigate the differentiation of neural progenitor cells (NPCs) following retinal transplantation in N-methyl-d-aspartate (NMDA)-treated eyes. NMDA was injected into the vitreous cavity of adult rat eyes. NPCs were prepared from telencephalic neuroepithelium of enhanced green fluorescence protein (EGFP) transgenic mice on embryonic day 14.5. A cell suspension was injected into the vitreous cavity in experimental eyes. Immunohistochemistry was conducted at 1, 2 or 4 weeks after transplantation of NPCs in an effort to determine the survival and differentiation of transplanted NPCs. Similar experiments were conducted using glycoprotein (gp)130-null (−/−) mice. Examination of retinal sections revealed that transplanted NPCs could survive for at least 4 weeks in NMDA-treated retinas. Immunohistochemical studies for specific cell-type markers revealed that, among the transplanted NPCs at 2 weeks after transplantation, the mean percentage (±standard deviation) of glial fibrillary acidic protein (GFAP)-positive (glial) cells was 63.5 ± 7.4%, demonstrating the differentiation of transplanted NPCs with a preference for the glial lineage. Furthermore, the mean percentage of βIII-tubulin-positive (mature neuronal) cells was 18.8 ± 4.5%. Following transplantation of NPCs isolated from gp130−/− mice into NMDA-treated retinas, the mean percentage of GFAP-positive cells (17.6 ± 7.0%), was significantly lower than that in NPCs isolated from wild-type mice (59.1 ± 6.0%, P = 0.04, Mann-Whitney U test). Preferential differentiation of NPCs into the glial lineage is induced through gp130 signaling in NMDA-treated eyes.