Neuro-protection and neuro-regeneration of the optic nerve: recent advances and future directions.
Neuro-protection and neuro-regeneration of the optic nerve: recent advances and future directions.
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DOI：
10.1097/wco.0000000000000777
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发表时间：
2020-02
影响因子：
4.8
通讯作者：
Lam P
中科院分区：
文献类型：
--
作者：
Gokoffski KK;Peng M;Alas B;Lam P
视神经病变是指视网膜神经节细胞(RGC)选择性受损的一组疾病，RGC是视网膜的专门神经元，其轴突组成视神经。继发于视神经病变的失明是不可逆转的，因为视网膜节细胞没有自我更新的能力，自我修复的能力有限。目前正在开发许多策略，以防止RGC进一步退化，或2)取代已退化的细胞。在这篇综述中，我们旨在讨论已知的中枢神经系统再生的局限性，然后讨论过去、现在和未来的视神经保护策略以及神经再生的方法，重点是过去两年的发展。中枢神经系统的神经再生受到内在因素和外在因素的限制。轴突再生的环境障碍可分为两大类：不能清除髓鞘和形成胶质瘢痕。虽然炎性瘢痕阻碍了轴突生长越过损伤部位，但炎症也提供了重要的信号，激活了视网膜节细胞的修复和再生途径。神经营养素作为单一疗法的神经保护在预防RGC退行性变方面并不有效，这可能是由于生长因子的快速清除所致。新的方法包括利用不同的技术来提供神经营养因子的持续输送。其他方法包括应用抗凋亡分子和抗轴突缩回分子。尽管干细胞正在成为一种可行的选择，以产生基于细胞替代的策略的视网膜节细胞，但在它们可以用于临床实践之前，仍有许多关键障碍需要克服。辅助治疗，如施加电场、支架和磁场刺激，可能有助于移植的视网膜节细胞向正确的方向延伸轴突，并有助于新突触的形成。不同的视神经疾病将从神经保护和神经再生方法中受益。开发临床有效的视神经疾病治疗方法将需要一种合作的方法，不仅使用神经营养因子，还包括促进轴突发生的信号，将轴突生长定向到预定的目标，并促进适当的突触发生。
Optic neuropathies refer to a collection of diseases in which retinal ganglion cells (RGCs), the specialized neuron of the retina whose axons make up the optic nerve, are selectively damaged. Blindness secondary to optic neuropathies is irreversible as RGCs do not have the capacity for self-renewal and have a limited capacity for self-repair. Numerous strategies are being developed to either 1) prevent further RGC degeneration or 2) replace the cells that have degenerated. In this review, we aim to discuss known limitations to regeneration in CNS, followed by a discussion of previous, current, and future strategies for optic nerve neuroprotection as well as approaches for neuro-regeneration, with an emphasis on developments in the past two years. Neuro-regeneration in the CNS is limited by both intrinsic and extrinsic factors. Environmental barriers to axon regeneration can be divided into two major categories: failure to clear myelin and formation of glial scar. Although inflammatory scars block axon growth past the site of injury, inflammation also provides important signals that activate reparative and regenerative pathways in RGCs. Neuroprotection with neurotrophins as monotherapy is not effective at preventing RGC degeneration likely secondary to rapid clearance of growth factors. Novel approaches involve exploiting different technologies to provide sustained delivery of neurotrophins. Other approaches include application of anti-apoptosis molecules and anti-axon retraction molecules. Although stem cells are becoming a viable option for generating RGCs for cell-replacement based strategies, there are still many critical barriers to overcome before they can be used in clinical practice. Adjuvant treatments, such as application of electrical fields, scaffolds, and magnetic field stimulation, may be useful in helping transplanted RGCs extend axons in the proper orientation and assist with new synapse formation. Different optic neuropathies will benefit from neuro-protective versus neuro-regenerative approaches. Developing clinically effective treatments for optic nerve disease will require a collaborative approach that not only employs neurotrophic factors but also incorporates signals that promote axonogenesis, direct axon growth towards intended targets, and promote appropriate synaptogenesis.