Exploring Optic Nerve Axon Regeneration

Abstract

Background: Traumatic optic nerve injury is a leading cause of irreversible blindness across the world and causes progressive visual impairment attributed to the dysfunction and death of retinal ganglion cells (RGCs). To date, neither pharmacological nor surgical interventions are sufficient to halt or reverse the progress of visual loss. Axon regeneration is critical for functional recovery of vision following optic nerve injury. After optic nerve injury, RGC axons usually fail to regrow and die, leading to the death of the RGCs and subsequently inducing the functional loss of vision. However, the detailed molecular mechanisms underlying axon regeneration after optic nerve injury remain poorly understood.Methods:Research content related to the detailed molecular mechanisms underlying axon regeneration after optic nerve injury have been reviewed.Results:The present review provides an overview of regarding potential strategies for axonal regeneration of RGCs and optic nerve repair, focusing on the role of cytokines and their downstream signaling pathways involved in intrinsic growth program and the inhibitory environment together with axon guidance cues for correct axon guidance. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which contributes to develop improved treatments for optic nerve regeneration. These findings are encouraging and open the possibility that clinically meaningful regeneration may become achievable in the future.Conclusion:Combination of treatments towards overcoming growth-inhibitory molecules and enhancing intrinsic growth capacity combined with correct guidance using axon guidance cues is crucial for developing promising therapies to promote axon regeneration and functional recovery after ON injury.

Models and treatments for traumatic optic neuropathy and demyelinating optic neuritis

“…In more detail, it has been shown that BDNF enhances RGC survival post-injury (Chen & Weber, 2001). Moreover, when BDNF is overexpressed specifically in the retinal tissue, the SMI-32+ large soma RGCs survival is promoted since these cells are more vulnerable to acute injury post-ONC (Feng et al, 2017). Finally, the combination of BDNF and the free radical scavenger S-PBN in a rat model of ON transection, showed an increase in RGC survival but not an improvement in long-distance axon regeneration.…”

“…The ON transection/axotomy (Figure 1a1) (Magharious, D'Onofrio, & Koeberle, 2011;Solomon et al, 1996;Vidal-Sanz, Bray, Villegas-Perez, Thanos, & Aguayo, 1987;Villegas-Perez, Vidal-Sanz, Rasminsky, Bray, & Aguayo, 1993), ON crush (ONC, Figure 1a2) (Selles-Navarro, Ellezam, Fajardo, Latour, & McKerracher, 2001;Tang et al, 2011;Templeton & Geisert, 2012), and ocular blast injury ( Figure 1b) (Hines-Beard et al, 2012) are the three classical models used for many years by researchers to study retinal and ON injury. While the ONC model allows for the investigation of effects on both the survival of retinal ganglion cells (RGCs) and axon regeneration, the axotomy model results in extended (more than 90% between two weeks and one month) cell death in the retina (Li, Sun, Yang, Zhu, & Feng, 2017;Villegas-Perez et al, 1993); thus, it is mainly used as a model for RGC apoptosis and survival. Axotomy is a highly invasive model, while there are many different protocols to crush the ON based on the methodology used and timing variations.…”

Updating traumatic optic neuropathy

“…Researchers continuously talk about axon regeneration and we found another article (Li et al, 2017) published last year that provides an overview regarding potential strategies for axonal regeneration of RGCs and optic nerve repair; it focuses on the role of cytokines and their downstream signaling pathways involved in intrinsic growth program and the inhibitory environment together with axon guidance cues for correct axon guidance. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which contributes to develop improved treatments for optic nerve regeneration.…”

Cell Replacement Therapy for Optic Nerve Disorders

“…A variety of diseases occur due to non functional axons within the optic nerve that result in loss of visual function. Traumatic optic nerve (ON) injury is the leading cause of irreversible visual impairment worldwide [7] . Optic nerve disorders severely impact vision in one or both eyes.…”

“…Hydrated collagen and N-isopropylacrylamide copolymer-based ECMs are fabricated. These are used in replacement therapy to improve nerve function mainly regeneration of defective neurons [104] . Extracellular matrix (ECM) macromolecules replicate within tissue-engineered biosynthetic matrices and influence cellular properties and behavior.…”