Receptor protein tyrosine phosphatase sigma inhibits axon regrowth in the adult injured CNS

Recently, receptor protein tyrosine phosphatase-σ (RPTPσ) has been shown to inhibit axon regeneration in injured peripheral nerves. Unlike the peripheral nervous system (PNS), central nervous system (CNS) neurons fail to regenerate their axons after injury or in disease. In order to assess the role of RPTPσ in CNS regeneration, we used the retinocollicular system of adult mice lacking RPTPσ to evaluate retinal ganglion cell (RGC) axon regrowth after optic nerve lesion. Quantitative analysis demonstrated a significant increase in the number of RGC axons that crossed the glial scar and extended distally in optic nerves from RPTPσ (−/−) mice compared to wild-type littermate controls. Although we found that RPTPσ is expressed by adult RGCs in wild-type mice, the retinas and optic nerves of adult RPTPσ (−/−) mice showed no histological defects. Furthermore, the time-course of RGC death after nerve lesion was not different between knockout and wild-type animals. Thus, enhanced axon regrowth in the absence of RPTPσ could not be attributed to developmental defects or increased neuronal survival. Finally, we show constitutively elevated activity of mitogen-activated protein kinase (MAPK) and Akt kinase in adult RPTPσ (−/−) mice retinas, suggesting that these signaling pathways may contribute to promoting RGC axon regrowth following traumatic nerve injury. Our results support a model in which RPTPσ inhibits axon regeneration in the adult injured CNS.