OPTIC NERVE REGENERATION IN MAMMALS: REGENERATED OR SPARED

SUMMARY In this review article, Fischer and colleagues examined controversies regarding the interpretation of the results of studies of optic nerve regeneration that use common crush models. They discussed typical outcomes in crush studies that serve as controls for validating actual regeneration of retinal ganglion cell (RGC) axons and reinnervation of central targets in studies of therapeutic interventions. The review compared morphologic and neurochemical differences between potentially regenerated axons and those that were spared in the putative total crush. Finally, the reviewers made several recommendations on how to promote more rigorous empirical practices and to facilitate the correct interpretation of results. DISCUSSION Why is the interpretation of axonal state difficult? As Fischer and colleagues pointed out, owing to its simplicity, intraorbital optic nerve crush is widely used to study factors that inhibit spontaneous RGC axonal regeneration and potential interventions to promote regrowth and reinnervation of brain targets. Nearly 1,000 PubMed results cite the keywords optic nerve crush. In these studies, however, even so-called complete or total crush can spare some RGC axons, thereby confounding the interpretation of results. Unless actually severed, axons have a certain pliability that allows them to become functionally quiescent for weeks after being crushed. Because of this property, intact axons can persist alongside those that were more severely damaged and may or may not show signs of regeneration. Even in the brain, functional quiescence of a few stressed—but not degenerated—RGC axonal projections can masquerade as newly reformed arborizations with appropriate innervation. These functional projections unpredictably influence the regenerative properties of nearby degenerated axons. Moreover, interventions designed to promote regeneration may influence injured but not completely severed axons in ways that differ from normal axons. How could investigations of optic nerve regeneration be improved? Fischer and colleagues noted that evidence interpreted as indicative of RGC axonal regeneration is often circumstantial, and they proposed new standards for the field. Following the lead of spinal cord injury investigations, one option for reducing or eliminating ambiguity would be to abandon crush in favor of transection. Although this improvement seems obvious, this is the age of murine transgenics, and total nerve SAVING THE OPTIC NERVE BY MELISSA L. COOPER, BS, AND DAVID J. CALKINS, PhD

**摘要** 在这篇综述文章中，费舍尔及其同事探讨了有关使用常见挤压模型的视神经再生研究结果解读方面的争议。他们讨论了挤压研究中的典型结果，这些结果可作为验证视网膜神经节细胞（RGC）轴突实际再生以及治疗干预研究中中枢靶点神经再支配的对照。该综述比较了潜在再生轴突与在假定的完全挤压中幸免的轴突之间的形态学和神经化学差异。最后，综述作者就如何促进更严谨的实证实践以及如何有助于正确解读结果提出了若干建议。 **讨论** 为什么轴突状态的解读很困难？正如费舍尔及其同事所指出的，由于其操作简单，眶内视神经挤压被广泛用于研究抑制RGC轴突自发再生的因素以及促进轴突再生长和脑靶点神经再支配的潜在干预措施。在PubMed上有近1000条结果引用了“视神经挤压”这一关键词。然而，在这些研究中，即使是所谓的完全挤压也可能使一些RGC轴突幸免，从而使结果的解读变得复杂。除非实际被切断，轴突具有一定的柔韧性，使其在被挤压后数周内处于功能静止状态。由于这一特性，完整的轴突可以与那些受损更严重的轴突并存，并且可能会或可能不会显示出再生的迹象。即使在大脑中，一些受到压力但未退化的RGC轴突投射的功能静止状态可能会伪装成具有适当神经支配的新形成的分支结构。这些功能性投射会不可预测地影响附近退化轴突的再生特性。此外，旨在促进再生的干预措施可能会以不同于正常轴突的方式影响受伤但未完全切断的轴突。 视神经再生的研究如何能够得到改进？费舍尔及其同事指出，被解读为表明RGC轴突再生的证据往往是间接的，他们为该领域提出了新的标准。借鉴脊髓损伤研究的做法，减少或消除模糊性的一个选择是放弃挤压而采用切断的方法。尽管这种改进似乎显而易见，但现在是小鼠转基因的时代，而且完全切断神经（此处似乎文本不完整） 作者：梅利莎·L·库珀，理学学士；大卫·J·卡尔金斯，博士