Return of function after CNS axon regeneration: Lessons from injury-responsive intrinsically photosensitive and alpha retinal ganglion cells

• Published in: Progress in retinal and eye research Vol. 71; pp. 57 - 67
• Main Authors: Berry, Martin, Ahmed, Zubair, Logan, Ann
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2019
• Subjects: Animals; Axons - physiology; CNS axon regeneration; CNS trauma; Crush Injuries; Disease Models, Animal; ipRGC; Myelin Sheath; Nerve Regeneration - physiology; Neuroprotection; Optic Nerve Injuries - metabolism; Optic Nerve Injuries - physiopathology; Recovery of function; Recovery of Function - physiology; Retinal Ganglion Cells - physiology; α-RGC; CNS axon regeneration; α-RGC; Recovery of function; Neuroprotection; ipRGC; CNS trauma
• ISSN: 1350-9462; 1873-1635
• DOI: 10.1016/j.preteyeres.2018.11.006

This review addresses issues relating to the survival and axon regeneration of both intrinsically photosensitive retinal ganglion cells (ipRGC) and αRGC, and possible ensuing patterns of functional recovery after optic nerve crush, all of which are broadly relevant to recovery from injury in the central nervous system (CNS) as whole. Although much needs to be clarified about the connectivity, function and patterns of myelination of regenerated CNS axons, the results of recent research on activity-induced αRGC axon regeneration associated with functional restitution have highlighted key focal obstacles to recovery including neurotrophic support, axon misguidance, target recognition failure and dysmyelination. Pan RGC survival/axon regeneration requires receptor binding and downstream signalling by a cocktail of growth factors, more generally defined in the CNS by the individual trophic requirements of neuronal subsets within a given disconnected centre. Resolution of the problem of failed axon guidance and target recognition is complicated by a confounding paradox that axon growth inhibitory ligand disinhibition required for axon regeneration may mask axon guidance cues that are essential for accurate re-innervation. The study of the temporal parameters of remyelination of regenerated αRGC axons may become feasible if they establish permanent homologous connections, allowing time for new myelin sheaths to fully form. Unless near complete re-innervation of denervated targets is re-instated in the CNS, debilitating dysfunctional neurological sequelae may ensue from the resulting imbalance in connectivity. •Less than 10% of retinal ganglion cell (RGC) axons regenerate despite the multiplicity of axogenic stimuli.•Five subtypes of intrinsically photosensitive RGC (ipRGC; M1-M5) are present in the murine retina.•Only M1 spontaneously survive optic nerve axotomy.•Only αRGC regenerate their axons and are mammalian target of Rapamycin (mTOR)-dependent.