Understanding intrinsic survival and regenerative pathways through in vivo and in vitro studies: implications for optic nerve regeneration

Introduction: Adult neurons in the mammalian central nervous system (CNS) do not regenerate after injury. One reason for this is a reduction in the intrinsic regenerative abilities of mature CNS neurons. Another reason is that the glial environment disturbs the axonal regeneration because the glial scar physically blocks axonal elongation. In addition, the degenerating myelin debris inhibits axonal regeneration biochemically. The optic nerve (ON) consists of the axons of the retinal ganglion cells and it is part of the CNS and researchers have selected the optic nerve crush (ONC) models for studying axonal regeneration of the CNS. We summarize the basic knowledge and the trends in the study of ON regeneration from the evidence obtained from both in vitro and in vivo experiments of ONC models. Areas covered: We searched the PubMed-MEDLINE data bases and gathered the evidence from published articles regarding ON regeneration from both in vivo and in vitro experiments. Expert commentary: The major intrinsic regenerative pathways for neural regeneration are the PI3K/ Akt/mTOR and JAK/STAT pathways. To overcome the inhibitory environment in the CNS, a stabilization of the growth cones is necessary. For this, not only neuroprotection but also multiple strategies are required for successful ON regeneration.

Automated summary

Adult neurons in the mammalian central nervous system do not regenerate after injury primarily due to reduced intrinsic regenerative pathways and inhibitory glial environment. Research focusing on optic nerve crush models has shed light on the basic knowledge and trends in CNS axonal regeneration. Expert suggest that stabilization of growth cones and multiple strategies are essential for successful optic nerve regeneration.