Intrinsic determinants of optic nerve regeneration.

Objective: To review the functions of these intracellular signals in their regulation of retinal ganglion cell (RGC) axon regeneration.

Data Sources: Relevant articles published in English or Chinese from 1970 to present were selected from PubMed. Searches were made using the terms "intrinsic determinants, axon regeneration, RGC, optic nerve regeneration, and central nervous system axon regeneration."

Study Selection: Articles studying the mechanisms controlling RGC and central nervous system (CNS) axon regeneration were reviewed. Articles focusing on the intrinsic determinants of axon regeneration were selected.

Results: Like other CNS neurons of mammals, RGCs undergo a developmental loss in their ability to grow axons as they mature, which is a critical contributing factor to the failure of nerve regeneration and repair after injury. This growth failure can be attributed, at least in part, by the induction of molecular programs preventing cellular overgrowth and termination of axonal growth upon maturation. Key intracellular signals and transcription factors, including B cell lymphoma/leukemia 2, cyclic adenine monophosphate, mammalian target of rapamycin, and Krüppel-like transcription factors, have been identified to play central roles in this process.

Conclusions: Intense effort and substantial progress have been made to identify the various intrinsic growth pathways that regulate RGC axon regeneration. More work is needed to elucidate the mechanisms of and the interrelationship between the actions of these factors and to successfully achieve regeneration and repair of the severed RGC axons.