Retinal ganglion cells (RGCs) are the projection neurons from the eye to the brain and their loss results in visual impairment in a number of diseases. Transcription factors with a homeodomain can translocate between cells and, in at least one reported case, can stimulate neuronal survival. Otx2 is a homeoprotein transcription factor expressed in the retina that is taken up by RGCs. We thus hypothesized that Otx2 capture could regulate the survival of adult RGCs. We report that Otx2 stimulates the survival of adult mouse and rat RGCs in vitro and protects RGCs against NMDA-induced toxicity in vivo in mice. In the latter model, Otx2 also preserves visual acuity.

These data suggest that Wnt/β-catenin signaling is a key downstream effector of MET signaling and contributes to the maintenance of GSC and GBM malignancy.